HAHN CONFIRMATION HEARING: Solid Performance Light On ... · to get you to review your answers and...

CONTINUED ON PAGE 4

FOR THE LATEST INSIGHT ON BIOPHARMA REGULATION AND POLICY, VISIT: PINK.PHARMAINTELLIGENCE.INFORMA.COM

Vol. 81 / No. 47 November 25, 2019

BIOSIMILARS

US FDA’s Stein: ‘Cognitive Dissonance’ Exists Between Review Divisions In Regulation Of Biosimilars, p. 16

REGULATORY UPDATE

CNS ‘Graveyard Of Drug Development’ Needs Oncology-Like FDA Regulatory Approach, p. 7

REGULATORY UPDATE

EMA Recharges Role In Non-EU Drug Approvals, p. 9

forthcoming, but President Trump now ap-pears to be backing away.

Hahn was asked repeatedly whether he would support a policy banning non-tobacco e-cigarette flavors when in office, but refused to take a definitive position. Hahn said he did not want to prejudge the final policy, which remains under consid-eration. He also said that as an oncologist, researcher, father and soon-to-be grandfa-ther, he takes the issue seriously.

“I don’t have all the facts that [the ad-ministration] might have, but I can tell you this for sure sir: I will use science and data to guide the decision if I am fortunate enough to be confirmed and I won’t back away from that,” Hahn said.

The answer did not sit well with some senators, including Doug Jones, D-AL, who said that Hahn’s non-answers on vaping during the hearing contrasted with the im-pression he gave during a private meeting.

“I just don’t think that was you. I think it was prep from handlers,” Jones said near the end of the hearing. “It’s going to require some courage to pull back and say you are damaging the health of so many children in this country … and I think you know that.”

“The question is how we go about do-ing it, it’s not a question of if we go about doing it,” Jones continued. “So I’m going to submit another question for the record sir. And that question is simply going to be to get you to review your answers and ask you to give a more thoughtful and opinion-ated, personal opinion, not about the de-tails of the rule, but about whether or not that what the administration’s pull back now is right or wrong and whether or not

HAHN CONFIRMATION HEARING: Solid Performance Light On SubstanceDERRICK GINGERY [email protected]

U S Food and Drug Administration commissioner nominee Stephen Hahn kept his answers to senators’

questions vague, sometimes irritatingly so, during his Senate confirmation hearing, and emerged largely unscathed from the 20 November event.

Hahn encountered nearly two hours of questions from the Health, Education, La-bor and Pensions Committee and pledged to work with senators’ requests on a variety of issues. However, he limited many of his positions to a commitment to review all relevant data and science, as well as follow the law, when making decisions, revealing little about his thinking.

The lack of detailed responses is in part by design. Hahn and the White House do not want him offering policy positions that

may endanger the confirmation vote or lead to problems once in office.

Hahn’s answers did not seem to bother HELP Committee Chairman Lamar Alexan-der, R-TN, who said that Hahn was a qual-ity nominee and that he looked forward to supporting him. Alexander said that he intends to schedule a committee vote on Hahn’s nomination for 3 December and would like the full Senate to confirm him before the end of the year.

The most questions from senators re-lated to drug development.

The second-most frequent questions concerned tobacco and, as expected, much of the hearing was dominated by vaping and senators’ concerns about a pending ban of e-cigarette flavors. The White House had indicated a ban was

FDA commissioner nominee Stephen Hahn waits for his Senate confirmation hearing to begin.

Phot

o cred

it: De

rrick

Ging

ery

PINK.PHARMAINTELLIGENCE.INFORMA.COM

mailto:[email protected]

FOR SPONSORSHIP OPPORTUNITIES CONTACT:Rob CoulsonE: [email protected]: +44 (0) 7825 845 666

FOR ALL OTHER ENQUIRIES:Natalie CornwellE: [email protected]: +44 (0) 7827 993 776

Open for EntriesTHE 25TH OTC MARKETING AWARDSEntry deadline: 6 December 2019

GALA DINNER & AWARDS PRESENTATIONTHURSDAY, 5 MARCH 2020 | ROYAL LANCASTER LONDON, UK

https://pharmaintelligence.informa.com/otc

Supported bySponsored by

JN2265 OTC Awards 2020 Open for Entries Advert US Letter.indd 1 2019/09/20 20:02

pink.pharmaintelligence.informa.com November 25, 2019 | Pink Sheet | 3

Industry Pricing Tactics Are Driving Europe’s Cross-Country Backlashhttps://pink.pharmaintelligence.informa.com/PS141240

A recent event in Brussels organized by the European Public Health Alliance found that cross-country initiatives on pricing and calls for more R&D and clinical trial transparency are gathering momentum in Europe, but there is still some way to go to address the imbalances in the system. The Pink Sheet spoke to EPHA’s Yannis Natsis about the issues raised at the organization’s fourth forum on medicines access.

ICER Will Explore Value Pricing For Cures In Context Of ‘Shared’ Health System Savingshttps://pink.pharmaintelligence.informa.com/PS141203

Future value assessments will include ‘hypothetical’ scenarios in which downstream medical savings will be shared between the health care system and the treatment developer.

US Insurers Must Disclose Rx Pricing, Cost Sharing To Members Under Proposed Rulehttps://pink.pharmaintelligence.informa.com/PS141212

Proposal from the Trump Administration seeks comment on whether the relationship between payers and pharmacy benefit managers would allow disclosure of rate information for drugs.

Co-Pay Charity Settles Charges It Conspired With Teva, Biogen, Novartis On Kickbackshttps://pink.pharmaintelligence.informa.com/PS141240

The Assistance Fund directed donations received from the companies to patients taking their multiple sclerosis drugs, the US Department of Justice announced. Further settlements may be pending.

Single Database Of FDA Actions Could Improve Drug Development, Sanofi Sayshttps://pink.pharmaintelligence.informa.com/PS141228

Sanofi exec advocates development of comprehensive dataset of US FDA regulatory processes and outcomes to enable sponsors to anticipate agency expectations.

exclusive online content

CO V E R Hahn Confirmation Hearing: Solid Performance Light On Substance

U S F D A 5 Drug Development Questions Dominate Hahn’s

Confirmation, Despite Talk About E-Cigs

R E G U L ATO RY U P D AT E 7 CNS ‘Graveyard Of Drug Development’ Needs

Oncology-Like FDA Regulatory Approach

9 EMA Recharges Role In Non-EU Drug Approvals

14 How Sustainable Is England’s Cancer Drugs Fund?

19 FTC Vote On BMS-Celgene Acquisition Splits Over Drug Pricing

21 New Deal To Boost Progress On African Medicines Agency

E M A 8 EMA Gets Keys To New HQ And Restarts Some Stalled Activities

D R U G R E V I E W S 11 Roche’s Polivy Among Seven New Drugs On Track

For EU-Wide Approval

B R E X I T 13 Pharma Declares Wishlist As Brexit Heightens

UK Election Stakes

R & D 15 Remote Decentralized Clinical Trials Could Solve RCT Problems

B I O S I M I L A R S 16 US FDA’s Stein: ‘Cognitive Dissonance’ Exists Between

Review Divisions In Regulation Of Biosimilars

M A N U FAC T U R I N G Q UA L I T Y 18 Generic Industry Not Sold On Benefits Of FDA Emerging

Technology Program

A D V I S O RY CO M M I T T E E S 22 Recent And Upcoming FDA Advisory Committee Meetings

inside: 13 9 11

pink.pharmamedtechbi.com

https://pink.pharmaintelligence.informa.com/PS141240





4 | Pink Sheet | November 25, 2019 © Informa UK Ltd 2019

U S F D A

these flavors should be banned right now.”Alexander appeared to defend Hahn’s an-

swers to the vaping ban questions, saying he did not think Hahn would take a position on the issue before he is confirmed.

“I don’t expect you to be able to state the position of an administration of which you are not yet a part,” Alexander said during the hearing. “I don’t see how you could do that.”

Indeed, Hahn’s vaping answers also may not offer many clues about his ap-proach to FDA operations, as some may have hoped. (Also see “Hahn Confirma-tion Hearing: Pharma May Be Left Parsing Non-Rx Questions For Policy Clues“ - Pink Sheet, 18 Nov, 2019.) But observers were able to judge how Hahn reacted to the Capitol Hill spotlight, and also heard his voice live for the first time. (Also see “The Most Important Hearing In Washington This Week – For Some Of Us, At Least” - Pink Sheet, 18 Nov, 2019.)

EXPERIENCE NOT A MAJOR TALKING POINT Hahn’s experience was not a significant issue during the hearing, other than a brief men-

tion by committee ranking member Patty Murray, D-WA, in her opening statement.

Murray said she had reservations about Hahn’s qualifications, in part because he has “no experience leading an organiza-tion anywhere near as complex as the FDA.”

Hahn currently serves as the chief med-ical executive of MD Anderson Cancer Center and spent most of his career in ac-ademic settings. (Also see “Stephen Hahn For US FDA Commissioner: Will Academic Experience Suffice For Confirmation?” - Pink Sheet, 1 Nov, 2019.)

Alexander argued in his opening state-ment that Hahn’s experience at MD An-derson will provide a “guiding hand” to the agency, and that his work at MD Anderson, the NIH and in the US Pub-lic Health Service Commissioned Corps. made him well prepared to run the FDA.

In answering a question about recruit-ing and retaining expertise at the agency, Hahn said MD Anderson, as a state-run institution, is strikingly similar to the FDA, in that both are complex, health-driven research organizations. He said his experi-ence recruiting and retaining talent at the cancer hospital will help at the agency.

REJECTING OUTSIDE INFLUENCES Hahn also received questions about his willingness to reject political or other influ-ences when making decisions.

Hahn said that he was committed to up-holding the FDA’s standards for safety and efficacy, in part because as a physician, he depended on the agency when treating patients. Hahn also recycled his vaping answers to address the question, saying that he would make decisions based on science, data and the law.

“I am deeply committed to my patients and the public health of the American peo-ple,” he said. “That is the most important and awesome responsibility of FDA and I com-mit to you that I will stand up for them.”

Scott Gottlieb, the FDA’s last confirmed commissioner, also was questioned about defending the agency against political in-fluence. Gottlieb said he was not afraid to speak up and would be guided by science. (Also see “Gottlieb’s Confirmation: He’s Will-ing To Disagree With Trump, Sec. Price” - Pink Sheet, 5 Apr, 2017.)

Published online 20 November 2019

CONTINUED FROM PAGE 1

The Original Forum for Bio/Pharma, Providing Exclusive Access to Executives and FDA/CMS Regulators to Examine Shifting Regulatory and Reimbursement Policy

REGISTER AT WWW.CBINET.COM/FDACMS • 800-817-8601

an informa business

Powered by: Proud Supporter: Media Partners:

December 3-4, 2019 • The Westin Arlington Gateway • Arl ington, VA

FDA/CMS Summit

Your Window Into Emerging FDA and CMS Regulatory Policies A�ecting Life Sciences

Powered by:

December 3-4, 2019 • The Westin Arlington Gateway • Arl ington, VA

FDA/CMS Summit

Your Window Into Emerging FDA and CMS Regulatory Policies A�ecting Life Sciences


U S F D A

Drug Development Questions Dominate Hahn’s Confirmation, Despite Talk About E-CigsMICHAEL CIPRIANO [email protected]

E ven though much of Stephen Hahn’s 20 November Senate confirmation hearing to become commissioner of

the US Food and Drug Administration fo-cused on e-cigarettes, a plurality of actual questions directed to the MD Anderson chief medical executive focused on drug development issues, similar to Scott Got-tlieb’s confirmation hearing in 2017.

Many members of the Senate Health, Education, Labor and Pensions Com-mittee discussed the FDA’s regulation of e-cigarettes, but a Pink Sheet analysis of the 67 questions asked by committee members identified 13 questions related to drug development. Tobacco-related questions came in a close second place with 10. (See graphic below.)

Drug development questions covered a wide range of areas within the subject. For instance, Sen. Chris Murphy, D-CT, in-quired about what the FDA can do help

facilitate development of products in ar-eas for which treatment advances have been lacking, such as for mental health.

“This is an area of particular interest to me,” Hahn said. “As you know, I’m a clinical trialist. And what endpoints we use … could help expedite some of this medical product development. We have to be pragmatic, but we also have to make sure they’re validated endpoints.”

Meanwhile, Sen. Mike Braun, R-IN, dis-cussed the idea of a of a novel “condition-al approval” pathway, for which he said he will be introducing a bill next week.

Under the pathway, Braun said, “drugs can be provisionally approved after re-ceiving promising early stage data … to address some of these diseases that have no cures and nothing really working well. The FDA could grant limited marketing authorization to new drugs after success-ful Phase I and Phase II clinical trials estab-

lishing safety and a reasonable expecta-tion of effectiveness, allowing patients in need of a treatment to benefit while al-lowing companies to generate a modest amount of revenue to fund Phase III trials.”

Hahn, when asked by Braun if he would support such an idea, responded that, “I think it’s important to expedite and have innovation reach patients as quickly as possible. I do want to make sure these approaches are validated so that we don’t make huge mistakes that hurt patients, but I am open to a conver-sation about all of those.”

Additionally, Sen. Tim Scott, R-SC, asked Hahn about working with Congress to support certain review divisions at the FDA that are less experienced in evalu-ating rare disease applications. (Also see “US FDA’s New Drug Assessors More Expe-rienced With Rare Disease Issues” - Pink Sheet, 11 Sep, 2019.)

Breaking Down Senate Questions To Stephen Hahn

Source: Pink Sheet analysis

Drug Development

Tobacco

FDA Standards

Opioids

Food

FDA Policy

GRx/Biosims/Drug Pricing

FDA Staff

Drug Shortages

Drug Importation

FDA Funding

OTC Policy

Personal

Devices

Bipartisanship

0 2 4 6 8 10 12

13

10

8

7

7

5

4

3

3

2

1

1

1

1

1

Number of Questions Asked




U S F D A

COMPARING (AND CONTRASTING) WITH GOTTLIEB’S QUESTIONSSimilar to Gottlieb’s confirmation hearing in 2017, a plurality of the questions at Hahn’s confirmation hearing focused on drug de-velopment. (Also see “Drug Development, Not Conflicts, Dominates Gottlieb’s Confirma-tion Hearing” - Pink Sheet, 10 Apr, 2017.)

Gottlieb received a series of ques-tions about accelerated approval, adaptive trial designs and improving review division performance.

Both Hahn and Gottlieb also fielded seven questions about opioids dur-ing their respective hearings. (Also see “Opioid Policy At US FDA: Gottlieb Seeks More Activist Role To Combat Abuse” - Pink Sheet, 6 Apr, 2017.)

One of Hahn’s questions on the topic came from Sen. Maggie Hassan, D-NH, who raised concerns about the use of enriched enrollment randomized with-drawal studies, which she contended

“skew the results” in favor of opioids.Unlike Gottlieb, however, Hahn spent lit-

tle time discussing generic drugs, save for a pledge to work with Scott on addressing a generic drug exclusivity “parking” provi-sion in the Lower Health Care Costs Act (S. 1895). (Also see “Senate Drug Pricing Legis-lation Clears Committee With Generic Exclu-sivity “Parking” Provision Unchanged” - Pink Sheet, 26 Jun, 2019.)

Gottlieb spoke at length about the de-velopment of complex generics during his hearing. (Also see “Complex Generics: Gottlieb Eyes FDA Policy Changes To Speed Approvals” - Pink Sheet, 5 Apr, 2017.)

Another notable difference is that Gottlieb had to field questions about his potential conflicts of interest due to his time in the private sector as a consul-tant and as a corporate board member for drug and medical device companies. Hahn meanwhile, has spent his career in academic medicine.

LACK OF GOVERNMENT EXPERIENCE SELDOM DISCUSSED One subject that was seldom broached by the committee was Hahn’s lack of sig-nificant governmental experience. (Also see “Hahn Confirmation Hearing: Pharma May Be Left Parsing Non-Rx Questions For Policy Clues“ - Pink Sheet, 18 Nov, 2019.)

The one lawmaker to raise the concern was Sen. Patty Murray, D-WA, who com-mented in her opening statement that, “I have some reservations regarding Dr. Hahn’s qualifications to lead the FDA. Dr. Hahn has almost no government experi-ence, no public record on policy issues related to the FDA, and no experience leading an organization anywhere near as complex as the FDA.”

Hahn was a commander in the US Pub-lic Health Service for six years, although he would be the first confirmed commis-sioner since David Kessler to have no sig-nificant federal administrative experience before taking over the FDA. (Also see “Ste-phen Hahn For US FDA Commissioner: Will Academic Experience Suffice For Confirma-tion?” - Pink Sheet, 1 Nov, 2019.)


Scott Gottlieb’s Confirmation Hearing Questions

Source: Pink Sheet analysis

Drug Development

FDA Standards

FDA Policy

Opioids

est

Drug Pricing

Food

FDA Staff

Tobacco

Antibiotics

Drug Safety

FDA funding

OTC policy

Personal

0 1 2 3 4 5 6 7 8 9 10 11 12

12

9

8

7

6

5

4

2

2

1

1

1

1

1

Number of Questions Asked

Sen. Murray expressed reservations about Hahn’s

lack of experience in government or in leading

an organization as complex as the FDA.

ANALYZEGo online for

more graphics analyzing the hearing discussion:

https://bit.ly/37sYPAZ

https://bit.ly/37sYPAZ


R E G U L A T O R Y U P D A T E

CNS ‘Graveyard Of Drug Development’ Needs Oncology-Like FDA Regulatory Approach BRENDA SANDBURG [email protected]

H ow can the US Food and Drug Administration promote develop-ment of drugs in the central ner-

vous system space? Katrin Rupalla, senior VP, head of regulatory affairs, medical doc-umentation and R&D quality at Lundbeck Inc., believes the agency should apply an approach similar to that used in oncology for products being developed for demen-tia and cognitive impairment.

Rupalla spoke at a meeting FDA con-vened for stakeholders to provide review staff in the Center for Drug Evaluation and Research’s Office of New Drugs (OND) with policy suggestions to promote ef-fective drug development programs that the agency could implement in the near-term. The call for recommendations comes as the office is undergoing a reor-ganization. (Also see “Drug Review Reor-ganization At US FDA Coming Into Focus” - Pink Sheet, 6 Nov, 2019.)

The 7 November meeting was remark-able for the number of agency officials in attendance. Twenty-five leaders of OND listened to 28 speakers discuss a wide vari-ety of topics. After each presentation, they asked questions to get more details on the recommendations. Stakeholders may also submit comments to FDA’s docket (FDA-2019-N-3453) through 7 January.

Rupalla said she chose to talk about CNS because it is exemplary of diseases in which there is a lack of understanding of the biology and there is a high unmet medical need. She noted that more than 700 million people are living with psychi-atric and neurological disorders globally and the number is expected to double between 2010-2030.

“The field is considered a graveyard of drug development, as seen with recent failures in Alzheimer’s programs,” she said.

The Danish CNS specialist has suffered its own setbacks. Earlier this year, its an-tipsychotic Rexulti (brexpiprazole) failed to meet the primary endpoint in treating

bipolar I manic episodes in two Phase III trials. (Also see “Pressure Builds On Lund-beck After Rexulti Fails In Bipolar I Manic Episodes” - Scrip, 15 Feb, 2019.)

And last year its schizophrenia treat-ment candidate LuAF35700 failed to meet the primary endpoint in a Phase III trial for treatment resistant schizophrenia. And Phase III trials of Rexulti for agitatation associated with dementia were deemed insufficent by FDA. (Also see “Lundbeck’s Rexulti Growth Hopes Clouded By Dementia Agitation Data Setback” - Scrip, 9 Feb, 2018.)

Rupalla contrasted the CNS area to that of oncology. She said the reason it is dif-ficult to apply breakthrough designations to CNS candidates and pick winners early on comes down to outcomes measures. While in oncology, you can measure the size of the tumor and its shrinkage, she said in CNS you must rely on question-naires, for example on whether a patient can walk, which often depend on mood or circumstances and which have a high placebo effect.

She said there is a need for new outcome tools and for frameworks for evidence col-lection in the real world. She also recom-mended having guidance on combination drug development similar to the oncology guideline about how to establish efficacy of each component in a regimen.

“We need to develop regulatory ap-proaches similar to oncology,” Rupalla said. She cited the Real-Time Oncology Review program, transdiagnostic approaches, breakthrough designations, and advance-ments in innovative trial design.

Launched last year, the Oncology Cen-ter of Excellence’s Real-Time Oncology Review pilot program gives the agency an early look at efficacy data for a supple-mental indication before an application is submitted. (Also see “Real-Time Oncol-ogy Review Has Sponsors Rethinking What Data To Share With US FDA And When” - Pink Sheet, 26 Nov, 2018.)

TRIAL DESIGNS, BIOMARKERS, AND SCIENTIFIC DEBATESRupalla said innovative trial designs, such as master protocols, are applicable in CNS as several neurological diseases have common symptoms, such as cognitive impairment and psychosis. In addition, she said there are common pathological hallmarks in neurological disorders, such as tauopathies.

Rupalla also emphasized the need for sponsors to have more opportunities to interact with FDA, not just with regard to a specific project but on broad scientific issues. She noted that FDA’s oncology divi-sion has met with the Friends of Cancer Re-search organization to provide a platform to push forward new methodologies, and agree on and prioritize the challenges.

“Debating the science, debating the challenge around methodology in scien-tific meetings with the agency would be very welcome,” she said.

Tiffany Farchione, acting director of the Division of Psychiatry Products, asked Ru-palla about use of the transdiagnostic ap-proach in CNS.

“I can see where that’s very appealing





in cancer where we know a lot about the pathophysiology of the illness right down to the genetics,” Farchione said. “In psychiatry we don’t have that” so it is difficult to say the pathophysiol-ogy of a symptom is the same in one disease versus another. She asked what FDA could do to encourage companies to explore pathophysiology, noting that the agency is also frustrated with relying on a ratings scale.

Rupalla replied that the easiest approach would be to start with something that’s well defined in the space, such tauopa-thies, to say that across these tauopathies you have a common symptom.

Another FDA official asked her to elab-orate on the absence of biomarkers. Ru-palla said that in CNS there is little patient sampling, other than spinal fluid and MRI, and genetic testing has not been fully implemented in the science of neurology in clinical trials. She noted that the more data that is accumulated the greater the possibility of finding genetic markers rel-evant for CNS diseases.

Rupalla said there must be a com-mitment from all parties to pursue this data collection. “If you find a mutation or if you find a common hallmark, would FDA be open to discussion based on this data and the use of this data in a submis-sion?” she asked.

The Center for Drug Evaluation and Research’s division of neurology prod-ucts has shown flexibility in the review of drugs for neurodegenerative diseases. (Also see “Biogen Aducanumab BLA Plan Is In Line With US FDA Neurology Division Precedent” - Pink Sheet, 10 Nov, 2019.)

In the area of Alzheimer’s disease, in-dustry has stepped up efforts to iden-tify biomarkers. Janssen Pharmaceutical Cos. and Shionogi & Co. Ltd. announced last month that they would work with the Alzheimer’s Discovery Foundation to provide broad access to tissue and blood samples from their discontinued development program for BACE inhibi-tors. (Also see “Alzheimer’s Biomarker Ben-efit From Failed Janssen BACE Inhibitor?” - Scrip, 23 Oct, 2019.)


EMA Gets Keys To New HQ And Restarts Some Stalled ActivitiesVIBHA SHARMA [email protected]

T he European Medicines Agency is running a recruitment exercise to replace staff members who have re-

signed or are planning to leave the agency because they do not want to relocate to the EMA’s new headquarters in Amsterdam.

The EMA was forced to shift its offices from London to Amsterdam following the Brexit referendum. On 15 November, the Dutch authorities handed over to the EMA a newly built tailor-made headquarters lo-cated in the Zuidas area of Amsterdam.

As a result of the recruitment drive, by June 2019, a total of 77 new staff mem-bers had joined the EMA as temporary and contract agents and national experts, the EMA’s executive director said in a 2019 mid-year report drawn up for the EMA’s management board.

The recruitment drive is to make up for the severe staff losses the EMA has been experiencing since 2018 – a trend that has continued through 2019. At the end of 2018, the EMA’s headcount was 901 but by October 2019 its available workforce was down to roughly 730. (Also see “EMA Under Pressure Again As Staff Losses Worsen” - Pink Sheet, 4 Oct, 2019.)

NEW OFFICE: TEMPORARY HALT ON FACE TO FACE MEETINGSSince its move to Amsterdam in March 2019, the EMA has been operating from temporary premises, the Spark building in Amsterdam Sloterdijk. The agency’s permanent office is now ready and staff are expected to move into the building in January 2020.

The EMA said that from 9 December to 10 January, most staff will work remotely. While equipment is shifted and IT systems are configured, no face-to-face meet-ings will take place in the week of 16-20 December, except for the EMA’s manage-ment board meeting on 18-19 December 2019, which will take place off-site. Also, there will be no face-to-face meetings

during the week starting 6 January.In the week of 13 January, the only

meetings to be held face-to-face are those of the EMA’s pharmacovigilance committee in the Spark building, and of the herbal medicines committee and sci-entific advice working party in the new building, the agency said.

ACTIVITIES BEING RESTOREDTo ensure that its core business activities were not affected by Brexit, the agency had launched a phased scale-back of non-essential activities via its business conti-nuity plan (BCP), but working under these

E M A

The EMA is running

a recruitment drive to

replace staff members

who resigned or

do not want to relocate

to Amsterdam.



conditions has “inevitably left a mark” on the agency’s 2019 work program, the mid-year report states.

Out of 147 activities listed in the work program, the report states that 79 are suspended, 18 have continued at a re-duced volume and pace, and only 50 have been maintained in their full scope. (Also see “EMA Chief Says Brexit Has Im-paired Ability To Support R&D“ - Pink Sheet, 8 May, 2019.) For example, development of the majority of scientific guidelines re-mained on hold and the development of only two oncology guidelines continued in Q1-Q2 2019, the report states. (Also see “Brexit Halts Work On 119 EMA Guidelines” - Pink Sheet, 8 May, 2019.)

Nevertheless, things are slowly getting back on track. As per the report, as of June 2019, the EMA started reinstating some of the activities it had earlier put on hold, with a focus on activities and projects that could increase the agency’s operational ef-ficiency so that it remains fit-for-purpose in the longer term, such as IT systems sup-porting medicines evaluation and the digi-talisation of administrative processes.

In addition, some of the EU network working groups directly contributing to EMA’s core activities are expected to restart.

The mid-year report lists activities, other than those deemed to be highest priority, that will continue in 2019. These include:

• Supporting effective and efficient con-duct of pharmacovigilance through product related support, such as planned access to and analysis of real-world data, and conducting planned surveillance using patient registries.

• Capturing and incorporating patients’ values and preferences into the benefit-risk evaluation of the scientific review process.

• Identifying areas in need of further science and innovation support for medicines development.

• Strengthening pharmacovigilance ca-pability across the network in the field of signal management and activities directly related to the EMA/HMA Big Data Task Force.


E M A

EMA Recharges Role In Non-EU Drug ApprovalsIAN SCHOFIELD [email protected]

T he European Medicines Agency is working on ways to entice more pharmaceutical compa-

nies to use its “Article 58” procedure, an assessment mechanism that was intro-duced in 2004 to increase the availability of medicines in non-EU countries with fewer regulatory resources and high un-met medical needs.

Article 58 allows the EMA’s drug evalu-ation committee, the CHMP, to give a scientific opinion on a marketing au-thorization application for a new drug or vaccine intended for a public health priority disease such as HIV or malaria, or for maternal or infant healthcare. The opinion can be used to support local registration procedures and it also facili-tates prequalification of the medicine by the World Health Organization (WHO).

While Article 58 is a very useful mech-anism for increasing access to medi-cines, it has been used only rarely since it was implemented. The EMA’s website lists just six products with valid assess-ment reports; four others obtained an opinion, but these were subsequently withdrawn for various reasons.

The most recent successful candidate was Sanofi’s fexinidazole product, which gained a scientific opinion for use in hu-

man African trypanosomiasis in late 2018.Following a 2015 review that high-

lighted numerous failings in the sys-tem, the EMA has been taking steps to increase the involvement of regulators and experts in Africa and elsewhere, improving communications on the ben-efits of the scheme, and revamping its guidance to make the process more at-tractive to companies.

According to Agnès Saint-Ray-mond, head of the EMA’s International Affairs Division, the agency has been do-ing a lot of work on regulatory capacity building in third countries and working more closely with the WHO. In addition, the Article 58 mechanism has been given the less arcane name of “EUMedicines4all.”

The EMA has also “engaged with stakeholders to make sure manufactur-ers, product development partnerships, national regulatory authorities, donors and procurers are involved and work with us,” Saint-Raymond said during a recent webinar organized by The Organ-isation for Professionals In Regulatory Affairs (TOPRA). The EMA also plans to widen the appeal of the process by al-lowing simultaneous assessments un-der both Article 58 and the EU central-ized procedure.






FAILINGS OF THE SYSTEMThe 2015 review of the scheme laid bare a raft of weaknesses in the Article 58 scheme, notably low awareness of its existence among local regulators, particularly in South East Asia and Latin America, and a lack of mechanisms for facilitating local reg-istration following the Article 58 opinion.

Moreover, the CHMP opinion under Arti-cle 58 was seen by some regulators as being of a lower standard because the product in question did not have an EU marketing au-thorization, Saint-Raymond said.

On top of that were the “quite costly” EMA fees for assessing a product that was specifically for use in low-resource set-tings, and the fact that the system had to compete with other schemes such as the US Priority Review Voucher, she noted. Poor coordination between the EMA and the WHO limited the potential benefits of the scheme for both national regulatory authorities (NRAs) and manufacturers, and there was some uncertainty around the overall benefits of the process.

The review did find some positive aspects of the scheme, though, such as the exper-tise of Stringent Regulatory Authorities (now renamed WHO-Listed Authorities), the benefits of scientific advice, and rapid inter-action between Article 58 and the WHO’s prequalification procedure – “these prod-ucts are immediately prequalified when they go through the Article 58 opinion.”

The results of the review led to the draw-ing up of five key proposals for improve-ments on which the agency has been work-ing since then, and now “we have done most of the work,” Saint-Raymond declared.

For example, the EMA has beefed up its communications, including making it clear to stakeholders that while the Article 58 fees are the same as for a centralized MAA, “it is possible to ask for a fee exemption or reduction by writing to the head of the EMA,” she noted.

The agency has also endeavored to accelerate reviews in low and middle in-come countries (LMICs) through capacity building and greater involvement of NRAs and regional regulatory networks in the Article 58 process.

On a wider level, Saint-Raymond said the EMA had been cooperating more closely

with core stakeholders such as donors, pro-curers and the WHO to simulate interest in using EU-Medicines4all and to “further embed it in the global health ecosystem. We have in particular started liaising with NGOs such as Médecins Sans Frontières.”

In order to get more NRA buy-in, the EMA has also begun working with the WHO to try and identify which experts and regula-tors should be invited to observe the proce-dure at the CHMP. “We bring them in during scientific advice and assessment, and en-courage them to join the session so they are fully informed. We are also increasing the number of in-person meetings and sharing materials earlier for the CHMP meeting, to make it better understood.”

Article 58 is now “part of our EU network strategy so it means it is really a core activi-ty of the EMA,” she stressed. She also point-ed out that the Article 58 procedure dove-tails with other mechanisms such as the EMA’s PRIME (priority medicines) scheme, which offers the possibility of an acceler-ated assessment, and the WHO’s collab-orative registration procedure, which is in-tended to speed up national approvals in countries where resources may be limited, based on assessment work already carried out by one regulatory body.

Despite the low number of Article 58 procedures to date, Saint-Raymond be-lieves the system has produced significant benefits where it matters – in the countries that need the medicines.

She said the CHMP opinions had led to a total of 138 regulatory approvals in 90 countries worldwide, with 62 of the ap-

provals in African countries. “We have mea-sured the impact of Article 58 and to our surprise we realized it is much bigger than we anticipated,” she declared.

SIMULTANEOUS ASSESSMENTSThe next step is to boost usage of the pro-cedure by allowing a drug to be assessed under Article 58 and the centralized proce-dure at the same time where the product is for use in both EU and non-EU countries. This is “all about making the procedure more attractive to companies and to limit use of resources,” Saint-Raymond said.

Under this approach the company would still make two submissions, but many aspects of the dossier, such as the quality and non-clinical parts, would be identical, thereby avoiding duplication of effort. Moreover, while there would be some specific requirements regarding tri-als in non-EU conditions, generally speak-ing the same trials would be contained in both submissions.

“For me it makes it more attractive, as products are generally for use in both populations,” Saint-Raymond said. It also addresses the perception of the EU hav-ing different standards as “we can show we have a simultaneous assessment and that we are assessing the same product at the same time with the same people, so it is not a second-level product, it is exactly the same. Of course there might be differences in the assessment but it doesn’t mean we use different standards.”

“We will still use experts and regulators of countries as we need to, and we will probably have two separate opinions for legal reasons and potential challenges,” she noted. She also cautioned that this ap-proach could result in a positive opinion for one population, for example in the EU, and a negative opinion for another. “It is important that we are clear on that.”

The EMA is currently working on imple-mentation of the simultaneous procedures, Saint-Raymond noted. As for when it might kick in, she said, with reference to the agen-cy’s Brexit-related relocation from the UK to the Netherlands and the resulting pressure on resources: “We will probably implement it in 2020 when we have more resources and time. Remember the EMA has been in

“We have measured

the impact of Article 58

and to our surprise we

realized it is much bigger

than we anticipated.”

– Agnès Saint-Raymond,

EMA



a difficult situation in 2019 and a number of activities have been postponed.”

THE PRODUCTSThe six products that have valid Article 58 assessment reports on the EMA website are:

• Fexinidazole Winthrop (sleeping sickness), Sanofi Aventis – opinion granted in 2019.

• Hexaxim (DTP, hepatitis B, polio and Haemophilus influenzae vaccine), Sanofi Aventis – 2017.

• Umbipro (chlorhexidine digluconate, prophylaxis of omphalitis), GlaxoSmithKline – 2016.

• Mosquirix (Plasmodium falciparum/hepatitis B vaccine), GSK Biologicals – 2015.

• Pyramax (pyronaridine plus artesu-nate, malaria), Medicines for Malaria Venture/Shin Poong – 2015.

• Aluvia (lopinavir/ritonavir, HIV treatment), Abbvie – 2010.

The opinions granted and subsequently withdrawn were:

• Hemoprostol (misoprostol/ Linepharma International) for post-partum hemor-rhage. The company was unable to obtain local MAs or market the product.

• Tritanrix (DTP/hepatitis B), GSK Biologi-cals. The MA lapsed and the product was discontinued.

• Lamivudine and lamivudine/zidovu-dine from ViiV. These were differently coloured versions of ViiV’s Epivir and Combivir and were withdrawn be-cause of limited sales and the cost of maintaining approvals.

One application, for GSK Biologicals’ Globorix (DTP, hepatitis B, invasive disease caused by H influenzae type b and Neisse-ria meningitidis serogroups A and C), was withdrawn by the company in 2007 be-fore the Article 58 opinion was given. GKS Biologicals said at the time that Globorix “does not fit in the current WHO vaccina-tion strategy in relation to meningococcal disease in the African meningitis belt.”


Roche’s Polivy Among Seven New Drugs On Track For EU-Wide ApprovalVIBHA SHARMA [email protected]

T he European Medicines Agency today said it had recommended for EU-wide marketing approval seven new drugs, including two orphans – Roche’s Polivy (polatuzumab vedotin), for treating diffuse large B-cell lymphoma (DLBCL), and

Novartis’s Isturisa (osilodrostat), for the treatment of Cushing’s syndrome.As was the case with Polivy’s approval in the US in June, the EMA’s drug evaluation

committee, the CHMP, has recommended that the drug receive a conditional approval for treating relapsed/refractory DLBCL in combination with bendamustine and Roche’s MabThera (rituximab). The recommendation for conditional marketing authorization means that Roche will likely have to provide comprehensive clinical data at a later stage. (Also see “Third Time Lucky for Roche’s Polivy in Europe?“ - Pink Sheet, 12 Nov, 2019.)

The CHMP considered the marketing authorization applications (MAAs) for the seven products during its latest monthly meeting, which took place on November 11-14 in Amsterdam.

The other five drugs recommended for pan-EU approval are:

• Novartis’s Mayzent (siponimod) for the treatment of adult patients with second-ary progressive multiple sclerosis (SPMS) with active disease evidenced by re-lapses or imaging features of inflammatory activity. If approved, Novartis said that Mayzent is expected to be the first and only oral treatment specifically indicated for patients with active SPMS based on a randomized clinical trial of a broad SPMS patient population. (Also see “EU: Stakes High For Novartis At Latest CHMP Meet-ing” - Pink Sheet, 13 Nov, 2019.)

• Jazz Pharmaceuticals’ Sunosi (solriamfetol) for treating excessive daytime sleepi-ness in narcolepsy and obstructive sleep apnea. Sunosi was approved in the US in March this year. (Also see “EU: Rigel And Jazz Among Hopefuls At CHMP” - Pink Sheet, 14 Nov, 2019.)

• Rigel Pharmaceuticals’ Tavlesse (fostamatinib) for the treatment of primary immune thrombocytopenia. The drug was approved in the US under the name Tavalisse in April 2018.

D R U G R E V I E W S




D R U G R E V I E W S

• Accord Healthcare’s generic drug, deferasirox, for treating chronic iron overload due to blood transfusions in patients with beta thalassemia and other anemias.

• Mylan’s generic drug, clopidogrel/acetylsalicylic acid, for the secondary prevention of atherothrombotic events.

Regarding Polivy, the CHMP adopted a positive opinion for the product’s use in combination with bendamustine and rituximab (BR) for treating adults with relapsed/refractory (R/R) DLBCL, who are not candidates for hematopoietic stem cell transplant. The committee’s opinion was based on the results of the Phase Ib/II GO29365 study, which Roche said was the first and only clinical trial to show higher response rates and improved overall survival compared to BR, a commonly used regimen, in this indication.

Datamonitor Healthcare analyst Zachary McLellan noted that Polivy in combination with BR had shown strong results and re-sulted in an “impressive” 66% reduction in the risk of progression or death compared to BR alone. The drug, however, comes with its side-effects and in the US, for example, “initial Polivy treatment is restricted to six cycles to limit instances of serious peripheral neuropathy that plagued an earlier trial and occurred at cycle five or later, potentially indicating a cumulative effect,” McLellan told the Pink Sheet.

Regarding the drug’s future, McLellan believes that Polivy’s “demonstrated efficacy and lower cost in comparison to next-generation treatments like the CAR-T therapies, will help it com-pete in R/R DLBCL patients ineligible for hematopoietic stem cell transplant where effective therapies remain an unmet need.”

The CHMP’s recommendations will now be forwarded to the European Commission for a final say on marketing authorization; these legally binding decisions should be made by the commis-sion within 67 days.

With the exception of Mylan’s clopidogrel/acetylsalicylic acid, the drugs that received a positive recommendation were listed in the CHMP’s meeting agenda as being up for an opinion from the committee. As per the meeting’s agenda, Mylan had been listed as being up for a possible oral explanation meeting regarding its MAA. These meetings are held when the CHMP still has major concerns about an MAA that would prevent it from adopting a positive opinion. As evidenced by the decision for clopidogrel/

acetylsalicylic acid, it is not unheard of for the CHMP to adopt an opinion in the same week as an oral explanation.

EXTENSIONS OF INDICATIONSAlso at the November CHMP meeting, the committee recom-mended extending the therapeutic indication of two marketed medicines: Roche’s Kadcyla (trastuzumab emtansine) and Cel-gene’s Revlimid (lenalidomide).

It said that the indication for Kadcyla should be extended to in-clude use of the product as a single agent for the adjuvant treat-ment of adult patients with HER2-positive early breast cancer who have residual invasive disease, in the breast and/or lymph nodes, after neoadjuvant taxane-based and HER2-targeted ther-apy. Roche said that this recommendation marked a significant step forward in bringing a potentially transformative treatment option to patients in Europe with HER2-positive early breast can-cer, who have residual invasive disease after neoadjuvant therapy.

As for Revlimid, the CHMP recommended the indication be ex-tended to include use of the product in combination with rituximab (anti-CD20 antibody) for the treatment of adult patients with previ-ously treated follicular lymphoma. If approved, Celgene said the drug would become the first combination treatment regimen for patients with follicular lymphoma that does not include chemotherapy.

WITHDRAWALSDuring the November meeting, the CHMP took note of three sepa-rate letters from companies that have withdrawn their respective submissions as it had become apparent to them that these would have received a negative opinion from the committee. (Also see “Jumping Before They Were Pushed – Kiadis And Aradigm Withdraw EU Filings” - Pink Sheet, 12 Nov, 2019.)

Two of these withdrawals were in relation to initial MAAs filed by Kiadis Pharma, for Luxceptar (viable T-cells), and Aradigm Phar-maceuticals, for Linhaliq (ciprofloxacin). The third withdrawal con-cerned Janssen’s application to extend the use of Opsumit (maci-tentan) to treat chronic thromboembolic pulmonary hypertension.

SAFETY WARNINGS CONFIRMEDThe CHMP also confirmed the recent safety warnings issued by its pharmacovigilance committee, the PRAC, regarding Sano-fi’s multiple sclerosis drug, Lemtrada (alemtuzumab) and Pfiz-er’s Xeljanz (tofacitinib), which is authorized for the treatment of rheumatoid arthritis, psoriatic arthritis and severe ulcerative colitis. (Also see “EMA Recommends Caution For Pfizer’s Xeljanz “ - Pink Sheet, 1 Nov, 2019.)


The CHMP’s recommendations go to

the European Commission for final

sign-off, generally within 67 days.

LET’S GET SOCIAL @PharmaPinksheet


B R E X I T

Pharma Declares Wishlist As Brexit Heightens UK Election StakesELEANOR MALONE [email protected]

T he UK pharmaceutical industry body ABPI has published a “2020 Manifesto for Medicine” targeting the political parties vying to win the country’s general election on 12 December.

With the country split over Brexit, parties have been drip-feeding a range of generous offers to entice voters. However, the two main parties, Conservative and Labour, have yet to publish their full elec-tion manifestos. No doubt mindful of the desperation of the com-peting parties, the pharma industry has now followed the biotech industry in laying out its expectations for the new government, while emphasizing its importance to the British economy.

Key demands include that money rebated under the branded drug spending cap be reinvested in increasing patient access to new medicines, and that the government maintains close ties with the EU on medicine regulation, trade in pharmaceutical supplies, R&D and ease of movement for research scientists. The ABPI also wants to see a modernization of the health technology appraisal body NICE.

In making these demands, the pharma industry reminds the gov-ernment that it has an annual turnover of £33bn, operates 860 sites in the UK and invests more than any other sector in R&D, with its £4.3bn annual expenditure representing a fifth of all business R&D spending.

The proposals in the Association of the British Pharmaceutical Industry’s manifesto cover:

• Access to medicines on the National Health Service including novel therapies, antibiotics and vaccines.

• Arrangements for Brexit and the post-Brexit relationship with the EU.

• Support for R&D in the UK.

• Tackling superbugs both domestically and internationally.

Like the BIA with its “Biotech Manifesto”, the ABPI is keen to pro-tect and promote the UK as a location for clinical trials. It is calling for increased collaboration between the NHS and the life sciences sector to increase the number of trials conducted in the UK.

It also wants to speed the uptake of novel therapies on the NHS, by reinvesting money rebated by the industry under the volun-tary pricing and access scheme – which caps spending growth on branded medicines at 2% a year for the next five years – in access and uptake initiatives.

It calls on the next government to apply cost-effectiveness thresholds “much more flexibly” and to “evolve NICE” to enable new medicines to reach NHS patients quickly. It also calls for a national vaccine strategy that would ensure people receive the vaccina-tions that are recommended for them.

When it comes to Brexit and the future relationship with the EU, the ABPI wants the government to secure a Brexit deal to mini-mize the disruption to the supply of medicines. It says the coun-try should be able to co-operate closely with the EU on medicine regulation even after the UK leaves the bloc, and calls on the gov-ernment to support “free and frictionless trade” of pharmaceutical supplies between the UK and European Economic Area, as well as securing reciprocal arrangements to enable free movement of re-search scientists and other highly skilled workers.

It urges the future government to secure the UK’s ongoing in-volvement in the EU’s Horizon 2020 scientific research program, not only as a participant but with the ability to design and influ-ence projects. As of June 2019, the UK had around 13,000 project participations in Horizon 2020, the second-highest number of project participations, and had secured €5.9bn of Horizon funding, representing 13.5% of the total, second only to Germany.

On R&D more generally, pharma wants the government to part-ner with industry to achieve its aim of boosting R&D investment to 2.4% of GDP by 2027, and up to 3% in the longer term. It wants the R&D tax credit and capital grant structure to be modernized to encourage R&D investment.

It also asks the government to use the unrecovered funds from its existing Apprenticeship Levy imposed on firms with a wage bill of more than £3m to create a new life sciences skills fund. This could be used to help address skills gaps for UK science in areas including genomics, immunology, bioinformatics and chemoinfor-matics, and clinical pharmacology.

Regarding antibiotics and antimicrobial resistance, a global health issue in which the UK has been an important leader, the ABPI wants the government to deliver on the existing five-year national action plan, maintain the UK’s global leadership in tackling AMR and work with industry to encourage R&D of new antimicrobials and vaccines. It has asked the government to introduce a “Netflix” style subscription model for new antibiotics. Earlier this year, the UK introduced a subscription-model pilot project whereby com-panies would be paid up front for new drugs on the basis of their expected value to the NHS rather than on the volume of drugs ac-tually used. (Also see “UK Plans Upfront Payment Scheme To Spur Antimicrobial Development” - Pink Sheet, 9 Jul, 2019.)






How Sustainable Is England’s Cancer Drugs Fund?FRANCESCA BRUCE [email protected]

T hough England’s Cancer Drugs Fund has improved access to oncology medicines, it fails to address some types of long-term uncertainty. To ensure the CDF’s survival, it will

need to evolve alongside the new types of treatment that are com-ing to the market, said Jennifer Lee, Janssen UK’s director of HE-MAR (health economics market access reim-bursement) and advocacy.

England could look to mechanisms used in other countries, such as treatment caps, said Lee, who was speaking at the ISPOR Eu-rope conference in Copenhagen, Denmark, this month (ISPOR is a professional society for health economics and outcomes re-search globally).

The second iteration of the CDF was established in 2016. The first fund ran be-tween 2010 and 2016 and was set up to ad-dress England’s comparatively poor uptake of new cancer medicines. It was intended as a stop-gap measure until a new value-based pricing system – that never materialized – was up and running.

The second version of the fund allows the health technology appraisal (HTA) institute for England and Wales, NICE, to recom-mend potentially cost-effective treatments, which have some un-certainty associated with them, for interim funding while more evidence is gathered.

Data are collected primarily through clinical trials and the Na-tional Health Service’s Systemic Anti-Cancer Therapy (SACT) data-set. Prior to the CDF, NICE was only able to recommend a drug for routine funding on the NHS or reject it altogether.

According to Lee, the CDF has been positive. Thanks to the fund, the proportion of cancer treatments rejected by NICE has fallen from 41% to 24%. “We would rather have conditional access up-front and allow the patients access as soon as possible to the most innovative medicines for high unmet need,” she said.

For some products, the fund is an appropriate mechanism, according to Lee. For example, those supported by data from single-arm Phase II trials where data on overall survival or com-parative efficacy from Phase III trials is expected within the rel-evant timeframe.

However, for others, the CDF may not be appropriate when it comes to addressing the relevant areas of uncertainty and is there-fore not a long-term solution for some drugs, said Lee. She pointed to the appraisal of Janssen’s Darzalex (daratumumab) as a mono-therapy for relapsed and refractory multiple myeloma. The drug was recommended for the CDF, areas of uncertainty identified re-lated to such things as overall survival, comparative effectiveness and subsequent treatment.

Lee does not expect to be able to address these particular con-cerns under the CDF. “We know when we get back to NICE it will be a struggle, but it was the right thing to do for patients,” she said.

In particular, uncertainty over comparative effectiveness will not be addressed. “The comparator really was a bunch

of old mixes of chemotherapy, none of which, had a license for those combina-tions for that place in therapy. So you will never collect that data, that comparator arm. You are never going to be able to demonstrate to NICE, for example, me-dian overall survival,” she said.

Lee also highlighted the NICE appraisal for Darzalex with bortezomib and dexa-methasone for previously treated mul-tiple myeloma.

Here the drug was used earlier in the treatment pathway and a Phase III study with the relevant comparator was under-way. As the data matured, the company was able to conduct some indirect analyses with relevant comparators.

However, NICE’s appraisal committee said that despite four years of follow-up data, median overall survival had not yet been reached. The company has predicted that overall survival-related uncertainty will be reduced as event rates have considerably re-duced. Nevertheless, the uncertainty will not be fully addressed as median overall survival will not be met at final analysis.

“You are basically saying over 50% of these patients will not have regressed or passed away.” Though this is “fantastic” for patients, it is unclear what it means from a NICE perspective. “It is uncertainty, how do you extrapolate survival curves?”

THE FUTUREThe issue will become more pressing given the types of therapies set to enter the market. “The emerging pipeline across the industry could impact the sustainability of the CDF,” said Lee.

These include medicines approved through accelerated licens-ing programs based on earlier data. This means that overall sur-vival data is likely to be immature. She also pointed to potentially curative treatments like cell and gene therapies.

But according to Lee, there are other ways to manage uncertain-ty and lessons can be learned from other countries, including Italy where outcomes-based deals are popular. If uncertainty is related to treatment duration, treatment caps could be used. And if it is related to overall survival, outcomes-based agreement based on surrogate endpoints could be used.


“We know when we

get back to NICE it will

be a struggle, but it was

the right thing to

do for patients.”

– Jennifer Lee, Janssen



R & D

Remote Decentralized Clinical Trials Could Solve RCT ProblemsFRANCESCA BRUCE [email protected]

E urope’s Innovative Medicines Initiative has launched a new project, Trials@Home, to evaluate how remote decentralized clinical trials (RDCTs), which use new technologies to allow

bigger, more diverse and remote populations to take part in clini-cal trials, could become the gold standard for clinical research. The project’s coordinator, Diederick Grobbee, explained to the Pink Sheet how RDCTs may replace traditional randomized control trials (RCTs).

The launch of the project came just before Janssen Pharmaceu-tical Cos. announced on 16 November its own decentralized trial to evaluate the effectiveness of Invokana (canagliflozin) in adults with heart failure, with or without type 2 diabetes. Janssen, which is also part of the Trials@Home project, says that all contact with participants in its trial will be done virtually, with no in-person clinical visits required.

According to Grobbee, “classical RCTs are, in certain therapeutic areas, almost impossible to sustain because of the size and cost of studies.” The growing demand for real world evidence and the emergence of big data analytics and new digital technologies is also driving demand for new paradigms, he said. Grobbee is also chief scientific officer at the Julius Clinical Academic Research Or-ganization in the Netherlands.

The Trials@Home project is funded by the IMI, a joint enterprise between the European pharmaceutical industry body EFPIA and the EU’s Horizon 2020 R&D innovation program. It is being run by a consortium of 31 members led by Sanofi and the University Medical Center Utrecht. The project will eventually conduct a pilot comparing an RDCT alongside an RCT and a hybrid model with the aim of establishing a set of guidelines that companies could use to conduct their own research.

The project will run for five years with a budget of €40m ($44.3m). Over that period, Groebbe hopes it will make big strides in using new innovative technologies such as apps and wearable devices to enable trials to be conducted remotely, and “bring them to patients rather than bring patients to the trials.” The consortium hopes that moving the trials from the traditional clinical setting, RDCTs will be faster and more efficient through the gathering of real world evidence.

New technologies include applications that monitor compli-ance, including smart phones. Grobbee also pointed to sensors that can measure certain things like glucose, blood pressure, heart rate and weight. And given the increasing interest in patient re-ported outcomes, these could also include technologies to allow patents to input data themselves, he said.

According to Grobbee, the model also allows for the collection of data from different sources, rather than relying on case report forms. For example, a combination of patient reported outcomes and data extracted from routine clinical data could be gathered, he said.

There is no limit on the type of medicines for which the RDCT

approach could work, said Grobbee. In chronic conditions, trials are generally very laborious and large, with up to 20,000 patients. “That requires massive resources and is extremely costly. They are difficult to sustain, and more cost-effective solutions need to be found,” he said. Meanwhile, it can be difficult to include rare disease patients in a trial if they live remotely and in different countries.

A LOT OF INTERESTThere have been few attempts at a wholly RDCT approach, accord-ing to Grobbee. Instead, he says many trials use “bits and pieces” of the concept but in a traditional setting. As such, the first phase of the project will explore an inventory of studies that are already conducted using new technologies to better understand how they are used and the possibilities that they lay open. In addition, stud-ies will be evaluated in terms of methodology and the regulations and ethical requirements associated with them.

Then, within two and a half years, the project will initiate a pilot comparing a wholly RDCT model with a traditional RCT and a hy-brid approach. The pilot will look at the impact of the type of study on the efficiency of trials, the quality of data and also how patients and physicians engaged in the studies.

The pilot should result in a set of recommendations that compa-nies can use to conduct their own trials, said Grobbee.

He thinks the pilot will last around six months and that the pharmaceutical used will be for a chronic condition, though this is yet to be confirmed. The project has had a lot of interest and a number of companies participating in the consortium have put their products forward for the pilot, he said. “We might have too much to choose from.”

The consortium also includes representatives from regulators, primarily the European Medicines Agency, and payers and health




R & D

technology appraisal bodies. As such there will be ongoing discus-sion about how trials will meet needs of payers and regulators, which will be reflected in the final guidelines.

JANSSEN’S DECENTRALIZED TRIALMeanwhile, Johnson & Johnson company Janssen last week said it had launched the “first ever ccompletely decentralized, mobile, indication-seeking study.”

According to Grobbee, the trial should provide useful informa-tion about RDCTs “alongside the thorough analyses made in Tri-als@Home.” However, he added that it is not “an exhaustive inven-tory or scientific assessment of the methodology which is the aim of Trials@Home.”

Janssen’s study, called CHIEF-HF, will assess the effectiveness of Invokana in adults with heart failure, with or without type 2 diabe-tes. It will compare Invokana against placebo on quality of life im-provement scales, in participants with either preserved or reduced ejection fraction heart failure. It will support clinical data from the Phase III program that supports Invokana.

The study will take place in the US and will enrol around 1,900 participants. All contact with trial participants will take place virtu-ally and no in-person clinical visits will be necessary, said the com-pany. This should “accelerate the study and fast-track the results,” it said. Smart devices and wearable devices will more quickly and efficiently gather and analyze real world data.

“Investigators will analyze participant-reported outcomes through app-based clinical questionnaires, and physical activity data as logged by an app on the smartphone and actigraphy data from a wearable activity device, including daily step count and stairs climbed,” Janssen said.

“Traditional clinical trials are undeniably essential in medical re-search but are often long and costly. Through the CHIEF-HF study, we are exploring how we can harness technology that consumers already have at their fingertips, including smartphones and wearable devices, to change this paradigm,” said Paul Stoffels, vice chairman of the executive committee and chief scientific officer at J&J.


B I O S I M I L A R S

US FDA’s Stein: ‘Cognitive Dissonance’ Exists Between Review Divisions In Regulation Of BiosimilarsMICHAEL CIPRIANO [email protected]

T he US Food and Drug Administration needs to overcome what Office of New Drugs (OND) director Peter Stein de-scribed as a “cognitive dissonance” among the various

review divisions to implement a consistent framework for the development and review of biosimilar products.

Biosimilar stakeholders have made a strong push for the FDA to im-plement a consistent regulatory approach that eases requirements for what they feel are unnecessary clinical trials for development. But Stein noted that the implementation of a uniform approach across the review divisions continues to be a work in progress.

“There is a little bit of a cognitive dissonance between the way many divisions are used to regulating and going to need to reg-ulate in the context of biosimilarity,” Stein said on 5 November at the Association for Accessible Medicines’ GRx+Biosims 2019 meeting. “And so there’s a tension.”

FDA review divisions have been used to regulating with a con-ceptual framework of what is needed to approve a new drug, and the Office of Therapeutic Biologics and Biosimilars (OTBB) has been working to push the review divisions to adopt a new conceptual framework of asking what is needed to establish bio-similarity or interchangeability, Stein explained.

“And I will say there’s lots of divisions that really do get it, the ones that are more experienced, and come to us with a mind around more efficient protocols,” Stein said. “And I think we’ve seen

You “can be assured that we are aligned

[with industry], I think, in the effort to

try to make these programs efficient

and as rapid as they can be, but still

holding standards that we want.”



B I O S I M I L A R S

several really innovative approaches that have been much more efficient, and haven’t said, ‘Go bring us 400- or 600 patient studies.’

“But I think you can be assured that we are aligned [with in-dustry], I think, in the effort to try to make these programs effi-cient and as rapid as they can be, but still holding standards that we want,” Stein continued.

The ongoing OND reorganization is a key agency effort in trying to improve reviewer consistency not only for biosimilars, but for other products as well, such as rare disease drugs. (Also see “Four Rules For Being A Consistent US FDA Reviewer From Peter Stein” - Pink Sheet, 9 Dec, 2018.) and (Also see “Drug Review Reorganization At US FDA Coming Into Focus” - Pink Sheet, 6 Nov, 2019.)

A LINGERING DISCONNECT? The necessity – or lack of necessity – of clinical trials for establishing biosimilarity was of dominant themes throughout the conference.

During a separate panel, Gillian Woollett, senior vice presi-dent at Avalere Health, argued that pharmacokinetic (PK) data is usually sufficient.

“If in Europe, the US, Canada and Australia, you look at the basis of approval, every single one where the PK matches, that product is approved,” Woollett said. “So what basis, what is the uncertainty upon what are you are saying that you need additional studies that are less sensitive, and cruder, and have to be very, very expensive?”

Sitting on the same panel as Stein, Gautier Sala, US head of biopharmaceutical regulatory affairs at Sandoz Inc., noted that clinical data are often variable and can add more “noise” to the review process.

Stein signaled he was receptive to these arguments. “Guidance very formally articulates the importance of being

able to use endpoints that can most sensitively detect differ-ences,” Stein said. “And we recognize that very often if there’s pharmacokinetic endpoints, obviously optimally those that directly tie to the efficacy endpoint. But even pharmacokinetic endpoints that provide a very clear profile can be considered.

“And we’ve had some very, I think, creative, vivid dis-cussions about how we can use those kinds of profiles, pharmacokinetic endpoints, as well as the clinical case study, and other evidence pulled together, a totality of evidence profile that doesn’t need us to require to say go and do three, four-indication studies, and come

back to us,” he continued.Sala said that Stein’s comments were “refreshing and reassur-

ing.” However, Sala argued that there is still a lingering disconnect between industry and the FDA on this point, referencing Stein’s previous remarks about the different regulatory approaches used by different review divisions.

“As mentioned, there is some variability across the FDA,” Sala said. “Whether there’s some confusion, what we’re discussing here is not necessarily coming through, really.”

Stein responded that Sala’s point was an important one. “I think we recognize that precision that one can hopefully get out of PK/PD, exposure-response and pharmacokinetic endpoints is great-er – and I think the guidance speaks to this – than clinical end-points, which often have greater variability,” Stein said.

The agency will look at clinical data if it shows worrisome differ-ences, Stein noted. But he added that “I think you can expect we’ll put that in the context of all of the evidence that we have, and not responding to differences that might be modest, that clearly are more likely noise than anything else. But again, each program and each dataset will be reviewed individually, and we will look at it. But I think you can expect that we will bring a lot of under-standing of the prior data before we make an assessment of the clinical studies, recognizing that clinical data can be variable.”

IT’S GOING TO TAKE MORE EXPERIENCE As the second decade of the US biosimilars experience is set to begin in 2020, FDA speakers expressed a sense of optimism that biosimilar development programs will continue to grow more ef-ficient over the subsequent 10 years.

Steven Kozlowski, director of the Office of Biotechnology Prod-ucts, commented that the development of better analytics will help in the streamlining effort.

“We have very good validation analytics, which are very, very powerful,” Kozlowski said. “But are there things that would reduce residual uncertainty? Are there PD markers, which may not be proven to be surrogates for efficacy, but would tell you so much about the biological impact of this that it’s really hard to say that there’s going to be a difference?”

Stein concurred, adding that the efficiency of development will continue to improve as the FDA review divisions continue to build on their experience with biosimilars.

“I think that what we’re going to see is as bioanalytics become even better and better, as we understand these molecules from a bioanalytic point of view, the information we have to be reas-

sured of comparability just rises,” Stein said.“And I think within FDA, as we gain more experi-

ence as the divisions get multiple biosimilar programs and learn more and have the regulatory framework of what’s a biosimilar versus new drugs, their comfort level and their … work with our OTBB staff in assuring we’re giving the most appropriate guidance to industry, I think that will move it forward.”


“ I think that what we’re going to see is

as bioanalytics become even better

and better, as we understand these

molecules from a bioanalytic point of

view, the information we have to be

reassured of comparability just rises.”

BE ALERTVisit our website at https://pink.

pharmaintelligence.informa.com

to sign up for daily email alerts.






M A N U F A C T U R I N G Q U A L I T Y

Generic Industry Not Sold On Benefits Of FDA Emerging Technology Program JOANNE S. EGLOVITCH [email protected]

P harmaceutical industry officials at-tending the Association for Acces-sible Medicines’ 4-6 November GRx-

Biosims meeting in North Bethesda, MD, said that there are a number of factors that preclude their participation in the US Food and Drug Administration’s Emerging Tech-nology Program despite the benefits the head of the program said emerging tech-nologies can deliver, such as more robust manufacturing processes and reduced risk of drug shortages.

Challenges include the high cost of de-veloping these technologies, the lack of outside support, and uncertainty as to whether these drugs would be approved under compressed timelines. There were also calls to change the regulatory frame-work for demonstrating therapeutic equiv-alence, and that the process is difficult and complicated enough without having an additional layer of complexity on top.

The FDA’s five continuous manufactur-ing approvals so far are all from innovators, not the generic industry.

GROWING ACCEPTANCES At the meeting, Larry (Sau) Lee, the leader of the ETT, said there have been over 50 acceptances into the program since its launch in 2014 to promote the use of new technologies in pharmaceutical manufac-turing. Thirty of them came last year. (Also see “FDA Reports Growing Use Of Process Modeling Tools To Support Continuous Man-ufacturing “ - Pink Sheet, 19 Nov, 2018.)

The agency only accepts such requests if they are from firms that are planning to submit investigational new drug applica-tions, original or supplemental new drug applications, abbreviated new drug appli-cations, biologics license applications or application-associated drug master files that involve emerging technologies.

The requests accepted to the emerging technology program include a continuous manufacturing application for a drug sub-

stance, continuous manufacturing of a drug product, pharmacy on demand, a model-based control strategy for continuous man-ufacturing, a model for continuous aseptic spray drying, a 3D printing manufacturing technology and an ultra long-acting oral formulation for a small molecules.

The five approvals of applications utiliz-ing continuous manufacturing are Vertex Pharmaceuticals Inc.’s Orkambi (luma-caftor/ivacaftor) approved in 2015, Janssen Pharmaceutical Cos.’s Prezista’s (darunavir) approved in 2016, Eli Lilly & Co.’s Verzenio (abemaciclib) approved in 2017, Vertex’s Symdeko (tezacaftor, ivacaftor) approved in 2018, and Pfizer Inc.’s Daurismo (glas-degib) approved in 2018.

FDA SAYS ETT A ‘GIFT’ TO INDUSTRY Lee said that the ETT is a “gift” to the drug industry, and adoption of innovative manufacturing technologies can promote more robust manufacturing and allevi-ate drug shortages. “If you think about it, one of the important things to really solve drug shortages right now and to solve the product quality issue is really to proactive-ly have new technologies that can ensure that you can produce your medicines in a consistent manner.”

The agency has an interest in promoting continuous manufacturing and other new technologies that can improve product quality, minimize product defects and re-duce drug shortages, and has been cham-pioning them for over a decade. (Also see “Continuous Manufacturing Poised to Disrupt Pharma Sector” - Pink Sheet, 29 Jul, 2014.)

Yet Ajaz Hussain, the president of the Na-tional Institute for Pharmaceutical Technolo-gy and Education (NIPTE), said in his presen-tation that there is little incentive for generic companies to sign up. He cited several fac-tors at play that preclude their participation.

One reason is the initial high cost of de-veloping these technologies. “How can ge-

nerics participate? It is a question mark; the challenge is very few generic companies can participate as brand companies can.” He also said there is a different mindset and a differ-ent business model for generic firms, which must meet more compressed timelines.

Hussain’s comments are aligned with those of AAM, which also raised concerns about cost in its comments to the FDA on its February 2019 draft guidance on continu-ous manufacturing.

AAM cautioned that the development and implementation of continuous manu-facturing may only be economical for large-volume, higher-margin products for which a company can have some assurance of mar-ket share. (Also see “FDA Continuous Manu-facturing Guidance Raises Concerns About Scope And Cost” - Pink Sheet, 6 Jun, 2019.)

Hussain said there is also the need for more outside support to help the generic industry develop these innovative tech-nologies. He said that “most of them need support, and the contract research manu-facturing model has to be considered.” He said there is also a need to explore the use of public and private partnerships to help the generic industry incorporate these technologies in manufacturing, and to educate and train a workforce in emerg-ing technologies.

Hussain added that the FDA also has to change its regulations for approving ge-neric drug applications before generics firms consider using emerging technolo-gies. He called this a “legacy” challenge. “The regulations have to change,” he said. “I look at the complete response letters and are they asking the right questions.”

CHANGE THE REGULATORY FRAMEWORK FOR GENERICS FIRST At the conclusion of the presentations, industry was pressed to explain why there is not more participation among generic ranks.



M A N U F A C T U R I N G Q U A L I T Y

Session moderator Bhagwant Rege of the FDA said that “we haven’t seen a whole lot of proposals from the generic in-dustry. Are there some issues that we can talk about? I want to hear from industry. What is causing the industry to not invest in these innovations?”

In response, Hussain reiterated that the FDA needs to change the regula-tory framework for approving generic drugs. “Unless you address how we re-view generic applications,” things will not change.

He cited the “scientific dispute” over generic mometasone as one example of the FDA’s rigid framework for establish-ing therapeutic equivalence. Hussain was referring to a first approval of a ge-neric version of inhaled corticosteroid Nasonex (mometasone furoate), a nasal spray. The ANDA was first submitted in December 2008 and approved eight years later on March 2016. He attributed the lengthy and protracted approval to a dispute over the particle size being dif-ferent from the brand product. Eventu-ally, the FDA issued a guidance says that a different particle size was permissible.

GENERIC OFFICIAL CITES ‘PREPONDERANCE’ OF QUESTIONS A generic industry official also said there are fears that it will take too long for the FDA to review ETT applications when there is always the rush to be first to file.

She said that “while we acknowledge the value of the ETT program and you have done a good job of explaining the benefit, as a generic company our job is to get an ANDA together, submit it, and get it approved as quickly as possible to get our product out on the market. Our perspective is that if we use any novel approaches there will be a preponder-ance of questions and it will be our re-sponsibility to present a volume of data to demonstrate how our novel technol-ogy is just as good and equivalent to the reference listed drug. This is counterin-tuitive to getting our product approved as quickly as possible.”


FTC Vote On BMS-Celgene Acquisition Splits Over Drug PricingBRENDA SANDBURG [email protected]

T he US Federal Trade Commission revealed a sharp divide in voting 3-2 to give the go-ahead for Bristol-

Myers Squibb Co.’s acquisition of Celgene Corp. with the divestiture of Celgene’s blockbuster psoriasis drug Otezla (apremi-last). The two dissenting commissioners said it was not sufficient to look solely at overlap-ping products and that high drug prices and other consequences of pharmaceutical mergers should be considered.

The FTC announced on 15 November that it had accepted a proposed consent order to remedy the anticompetitive effects result-ing from the proposed transaction. Dissent-ing statements by Democrat commissioners Rohit Chopra and Rebecca Kelly Slaughter,

and the response by Republican commissioner Noah Joshua Phillips, were striking in their tone and substance. The division shows how drug pricing has become a factor in the enforcement arena and could impact future pharma deals.

BMS unveiled plans to buy Celgene for $74bn in January, and in June announced that it was seeking a buyer for Otezla to address FTC concerns about the deal’s competitive harm to the psoriasis market. Otezla overlaps with a BMS late stage pipeline product, an oral, selective tyrosine kinase 2 (TYK2) inhibitor, BMS-986165, that is likely to be the next entrant into the market. (Also see “In Merger Plot Twist, BMS Needs A Buyer For Celgene’s Otezla, Raising New Questions” - Scrip, 24 Jun, 2019.)

Amgen subsequently said it would purchase Otezla for $13.4bn pending BMS’s clos-ing of the Celgene acquisition and FTC clearance. (Also see “Amgen’s $13.4bn Otezla Buy Helps Bristol/Celgene Merger Close By Year-End” - Scrip, 26 Aug, 2019.)

The FTC said the divestiture is the largest that the commission or the US Department of Justice has ever required in a merger enforcement matter.

‘COMPLETE SET OF HARMS’ SHOULD BE UNEARTHEDChopra said that with few exceptions, many FTC commissioners have primarily scru-tinized pharmaceutical mergers based on an examination of whether there are any product overlaps between the merging corporations, or where there may be clear-cut incentives to foreclose rivals with the ability to compete.

“I am deeply skeptical that this approach can unearth the complete set of harms to patients and innovation, based on the history of anticompetitive conduct of the firms seeking to merge and the characteristics of today’s pharmaceutical industry when it comes to innovation,” Chopra stated.

“Drug pricing is out-of-control and innovation is too slow,” he said. “When it comes to life-saving pharmaceuticals, the Federal Trade Commission should never ignore serious warning signs that most Americans see clearly.”

Chopra asserted that the BMS-Celgene transaction “appears to be heavily motivated by financial engineering and tax considerations (as opposed to a genuine drive for greater discovery of life-saving medications), without clear benefits to patients or the public.”






Chopra also expressed concerns about Celgene’s apparent history of anticompetitive behavior. In a footnote, he refers to an FDA list published last year of drug makers that were subject of complaints that they had restricted generic companies from accessing drug samples. He said Celgene was a top recipient of these complaints. (Also see “REMS Abuse Website: Celgene, Acte-lion Top List Of Suspected ‘Gamers’” - Pink Sheet, 18 May, 2018.)

Slaughter also asserted that the commission should more broadly consider whether any pharmaceutical merger is likely to exacerbate anticompetitive conduct by the merged firm or to hinder innovation. She said the FTC should study the effects of recent consummated mergers on drug research, development, and approval and should “unleash the full scope of our author-ity under Section 5 [of the Federal Trade Commission Act] to combat high drug prices.”

In a footnote, Slaughter said the commission has not recently litigated pharmaceutical merger cases, adding “we simply do not have a contemporary body of pharmaceutical merger case-law to clarify the boundaries of our analytical approach.”

HARM TO COMPETITION IS ONLY CONSIDERATION, PHILLIPS SAYSResponding to Chopra and Slaughter, Commissioner Noah Joshua Phillips asserted that the parties get to merge unless the commission can show a harm to competition.

“The dissenting commissioners both criticize the Commis-sion’s investigations of pharmaceutical mergers generally, ex-pressing concern that they fail to capture all the harms to com-petition posed by such mergers,” Phillips stated. “But, again, the most they offer is speculation about vaguely articulated harms, without any reference to any evidence that this merger is likely to exacerbate them. Nor do the dissenters cite a previous case that resulted in anticompetitive effects that they insinuate the Commission missed.”

“Our job is not to opine on whether a merger is ‘good’ or ‘bad’ for society as a whole, or to use our authority to make sure firms merge for reasons that someone might like (innovation) as op-posed to reasons that they may not (tax),” he stated.

In a separate statement, Commissioner Christine Wilson said that all members of the commission, including Chopra and Slaughter, agree that the only evidence of harm to competition that staff found was in the oral products that treat moderate-to-severe psoriasis, and all agree that the remedy was a divestiture of Celgene’s products and associated assets in this area.

She stated that there is no reason to believe there will be re-duced innovation in the pharmaceutical industry as a result of this transaction. She noted that no fewer than 711 companies are conducting late-stage research and development in oncol-ogy, the therapeutic category in which BMS and Celgene con-duct research.

Wilson said she agreed that pharmaceutical price levels in the US are a cause for concern but said many of the causes of higher drug prices fall outside the jurisdiction and legal authority of the commission.

DEMOCRAT COMMISSIONERS BRING A ‘NEW PERSPECTIVE’All five FTC commissioners were nominated and confirmed to the commission last year. Chopra and Slaughter are Democrats and Phil-lips, Wilson and FTC chairman Joseph Simons are Republicans. (Also see “Will FTC Shakeup Impact Pharma?” - Pink Sheet, 12 Feb, 2018.)

Andre Barlow, of Doyle, Barlow & Mazard, said the Democratic commissioners are “bringing a new perspective largely because of the dramatic ever-increasing list prices of drugs over the last several years.”

“Both are questioning whether the cookie cutter approach that has been used by the FTC for years to take care of competition concerns in these important markets is sufficient,” Barlow, a former DOJ trial attorney, said. “This all goes to the debate on whether the FTC should continue to follow its traditional analysis of focusing on horizontal product overlaps or whether it should take a more com-prehensive approach to determining whether these mega phar-maceutical mergers may be reducing competition in other areas.”

The split among commissioners may reflect a closer scrutiny of biopharma mergers by the FTC. Many in industry were surprised when Spark Therapeutics Inc. reported in a US Securities and Ex-change Commission filing in July that its merger with Roche could be delayed until April 2020.

At that time, David Balto, former policy director of FTC’s Bureau of Competition, said that a harder line on merger and acquisition reviews was being driven partly by public outrage over the high price of drugs. (Also see “When It Comes To FTC M&A Review, The Times May Be A Changin’” - Pink Sheet, 18 Jul, 2019.)

30-DAY COMMENT PERIOD In its complaint over the merger, the FTC said Otezla is the most significant oral product approved in the US to treat moderate-to-severe psoriasis and that BMS’ product is the most advanced oral treatment in development and would compete directly with Ote-zla. The complaint alleges that the acquisition would substantially lessen competition and “tend to create a monopoly” eliminating future competition between BMS and Celgene in developing, manufacturing and selling oral products to treat moderate-to-severe psoriasis.

The complaint notes that several older oral generic products, in-cluding methotrexate and acitretin, are approved by the US Food and Drug Administration to treat psoriasis that does not respond to topical medication and light therapy. But it says most doctors now prescribe agents that have better efficacy, better safety, or a more favorable side effect profile for patients with moderate-to-severe psoriasis who desire an oral treatment.

The consent order is to be published in the Federal Register short-ly and is open to public comment for 30 days after publication.

The order says that Quantic Regulatory Services shall serve as a monitor to ensure that the parties comply with their obligations. It also allows the commission to appoint a trustee in the event that BMS and Celgene fail to divest the Otezla products as required.




New Deal To Boost Progress On African Medicines AgencyIAN SCHOFIELD [email protected]

T he World Health Organization and the African Union have signed a memorandum of understanding to

formalize their cooperation in three areas, including the ongoing establishment of the future African Medicines Agency that will oversee and coordinate national drug regulatory activities on the continent.

The MoU was signed on 18 November. It also contains new commitments on strengthening disease control and preven-tion efforts in Africa and on fostering ef-forts to implement Universal Health Cover-age (UHC) across the continent as outlined in a “Call to Action” endorsed at the African Union Summit in Addis Ababa, Ethiopia, earlier this year.

“This deepened partnership will help to facilitate the necessary political support, and implementation of country-level in-terventions, needed to improve the health and well-being of people across the Afri-can continent,” said Moussa Faki Mahamat, chair of the African Union Commission, and WHO director-general Tedros Adha-nom Ghebreyesus.

The African Medicines Agency has been under development since it was first pro-posed in 2010, with support from the WHO, the African Union and the AU’s de-velopment agency NEPAD.

A draft treaty establishing the agency was drawn up in August 2017 and was ad-opted by AU health ministers meeting as a working group of the Specialised Techni-cal Committee on Health, Population and Drug Control in May 2018. (Also see “Afri-can Countries Adopt Treaty To Set Up New Medicines Agency” - Pink Sheet, 22 May, 2018.) The treaty was endorsed by African heads of state at the 32nd African Union summit in Addis Ababa, Ethiopia, in Febru-ary this year.

The AMA is a key part of the African Medicines Regulatory Initiative (AMRH), which is intended to strengthen and align regulatory practices across countries and

regional communities in sub-Saharan Af-rica and to improve patient access to safe, effective and high-quality medicines.

The new body is not intended to be a standalone regulator with a role in drug approvals such as the European Medi-cines Agency, for example.Rather, it will aim to guide and promote the adoption and harmonization of regulatory poli-cies, standards and guidelines at regional level as well as providing input to regula-tory actions and emerging health issues and pandemics. It will also take steps to tackle the problem of substandard and falsified medicines.

Tedros, who was Ethiopia’s health minis-ter from 2005 to 2012, said that investment in regulatory capacity building in Africa was “very important.” Noting the recent EU approval of Merck’s Ebola virus vaccine, Er-vebo, he said “the idea is to build that type of capacity in our countries.”

Access to high-quality, safe and effective medicines was “a core pillar of UHC,” he de-clared, adding that “we welcome the Afri-can Union’s decision to endorse the treaty establishing the AMA” and that the WHO “stands ready to provide further support to define the scope of activities and to pro-vide high-quality technical expertise.”

In particular, he said, “we are devoted to creating an enabling environment to foster local production, which is central to the Af-rican Medicines Agency’s work. A WHO mis-sion has just come back from Addis Ababa to discuss the details related to our support.”

The AMA cannot come into operation until the governments of at least 15 of the 55 AU member states have ratified it. It is understood to have been ratified by six countries as of 22 October: Algeria, Mada-gascar, Rwanda, the Saharawi Arab Demo-cratic Republic, Morocco and Zimbabwe. Last month Zimbabwe’s health and child care minister Obadiah Moyo said that his country would be among those bidding to host the secretariat of the agency because

it already has a functioning regulatory body and has been selected as the imple-menting agency for the AMRH.

The development of the AMA’s strategy and business plan is being led by the Bos-ton Consulting Group in cooperation with the AU Commission, NEPAD and other part-ners. The strategy and business plan are ex-pected to be ready by the end of the year.

OTHER AREASThe second area covered by the MoU is strengthening collaboration between the Africa Centres for Disease Control and Pre-vention (Africa CDC) and the WHO, with a specific focus on emergency preparedness so as to build up AU member countries’ de-fences against epidemics and other health emergencies.

Tedros said the current Ebola outbreak in the Democratic Republic of Congo was “a stark reminder that many AU countries are vulnerable to the impact of epidemics.”

Thirdly, the agreement will help to sup-port the implementation of the Call to Action on UHC, which Tedros said repre-sented “a very strong commitment to in-creasing domestic funding, which is essen-tial for achieving UHC.”

Tedros said the best investment in UHC was in primary health care, with a focus on promoting health and prevent-ing disease, rather than simply managing diseases in hospitals. “That’s why WHO is calling on all countries to increase their investment in primary health care by 1% of GDP, either through new investments, reallocation or both. To make that hap-pen, WHO will facilitate dialogue be-tween Finance and Health Ministers to help countries develop strong and sus-tainable health financing models.”




example.Rather


A D V I S O R Y C O M M I T T E E S

EDITORS IN CHIEF Ian Haydock (Asia)Eleanor Malone (Europe)Denise Peterson (US)

EXECUTIVE EDITORSPOLICY AND REGULATORYMaureen Kenny (Europe)Nielsen Hobbs (US)

COMMERCIALAlex Shimmings (Europe)Mary Jo Laffler (US)

ASIAAnju GhangurdeVibha RaviJung Won ShinBrian Yang

EUROPENeena Brizmohun Francesca BruceAndrea Charles

John DavisKevin GroganAndrew McConaghieIan SchofieldVibha Sharma Jo ShorthouseSten Stovall

USMichael CiprianoBowman CoxJoanne EglovitchEileen FrancisDerrick GingeryJoseph HaasMandy JacksonCathy KellyJessica Merrill Leah Samuel Brenda SandburgBridget SilvermanMalcolm SpicerSue Sutter

TO SUBSCRIBE, VISITpink.pharmaintelligence.informa.com

TO ADVERTISE, [email protected]

EDITORIAL OFFICE605 Third, Floor 20-22 New York, NY 10158 phone: 240-221-4500

CUSTOMER [email protected]

US Toll-Free ...................+1 888 670 8900US Toll .............................+1 908 547 2200UK & Europe .................+44 (20) 337 73737Australia .........................+61 2 8705 6907Japan ...............................+81 3 6273 4260

All stock images in this publication courtesy of www.shutterstock.com unless otherwise stated

© 2019 Informa Business Intelligence, Inc., an Informa company. All rights reserved.No part of this publication may be reproduced in any form or incorporated into any information retrieval system without the written permission of the copyright owner.

LEADERSHIPPhil Jarvis, Mike Ward, Karen Coleman

SUBSCRIPTIONSDan Simmons, Shinbo Hidenaga

ADVERTISINGChristopher Keeling

HEAD OF PUBLICATION DESIGNGayle Rembold Furbert

DESIGNJean Marie Smith

Recent And Upcoming FDA Advisory Committee Meetings TOPICS ADVISORY COMMITTEE DATE

Correvio International Sarl’s vernakalant for rapid conversion of recent onset atrial fibrillation to sinus rhythm

Cardiovascular and Renal Drugs Dec. 10

Horizon Pharma’s teprotumumab for active thyroid eye disease Dermatologic and Ophthalmic Drugs Dec. 13

Durect’s Posimir (bupivacaine extended-release) for post-surgical analgesia Anesthetic and Analgesic Drug Products Jan. 16

LET’S GET SOCIAL @PharmaPinksheet

mailto:clientservices%40pharma.informa.com?subject=

Are you looking to reach and do business with senior decision makers in pharma and medtech?

To fi nd out how our team can help visit:https://pharmaintelligence.informa.com/marketing-services

We off er a range of marketing opportunities whether you are looking to:

• Raise brand awareness

• Produce content marketing/thought leadership content

• Generate leads

• Engage directly with potential clients as well as cementing existing relationships

JN2181 Marketing Services Advert US Letter.indd 1 2019/06/04 17:35

GENERAL INQUIRIES:Jo KirkpatrickT: +44 (0) 20 7017 7180E: [email protected]

SPONSORSHIP & TABLE BOOKING INQUIRIES:Christopher KeelingT: +44 (0) 20 3377 3183E: [email protected]

Open for EntriesCiteline Awards 2020

Thursday, April 30, 2020 | Hyatt Regency Boston, Boston, MAwww.clinicalresearchexcellence.com

Sponsored by

(Previously known as the CARE Awards)

Entry deadline: January 17, 2020

JN2783 Citeline Awards 2020 Open for Entries Advert US Letter.indd 1 2019/11/04 13:59

HAHN CONFIRMATION HEARING: Solid Performance Light On ... · to get you to review your answers and...

Documents

Transcript of HAHN CONFIRMATION HEARING: Solid Performance Light On ... · to get you to review your answers and...