Q3 2018 OUTLOOK REPORT EXTRACT - Pharma Intelligence/media/In... · I testing for glioma....

July 2018 / 1

Biomedtracker Q3 2018 Outlook Report

Q3

2018 OUTLOOK REPORT EXTRACT

July 2018 / 2


Summary In this report, we cover catalysts from 23 drugs expected to occur in Q3 2018. For each drug, the likelihood of Phase/PDUFA review success and overall Likelihood of Approval (LOA) given their particular phase, drug class, and disease group are provided. The results of the catalysts highlighted in our Q2 2018 Outlook Report can be found on Page 4. At the end of this report, we have included a list of Large Impact catalysts through Q3 2018. The catalyst list is also provided in Excel by downloading the supplemental material at the top of this page.

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About the Author Biomedtracker is an independent research service that offers proprietary clinical assessments of developmental drugs within a comprehensive and intuitive drug information database. Clients from the pharmaceutical, biotech, and investment industries rely on Biomedtracker for its insight on the likelihood of approval, commercial potential, and future data and regulatory catalysts for drugs within the competitive landscape of every important disease and indication. Over recent years, Biomedtracker has become the leader in providing objective information alongside evidence-based clinical assessments and investment research on pipeline drugs worldwide. For more information on getting direct access to Biomedtracker, please email [email protected].

Disclaimer Copyright © 2018 Sagient Research

This report is published by Sagient Research (the Publisher). This report contains information from reputable sources and although reasonable efforts have been made to publish accurate information, you assume sole responsibility for the selection, suitability and use of this report and acknowledge that the Publisher makes no warranties (either express or implied) as to, nor accepts liability for, the accuracy or fitness for a particular purpose of the information or advice contained herein. The Publisher wishes to make it clear that any views or opinions expressed in this report by individual authors or contributors are their personal views and opinions and do not necessarily reflect the views/opinions of the Publisher.

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Contents Of Full Report Outcomes of Biomedtracker's Large Impact Catalysts from the Q2 2018 Outlook Report ........................... 4

Tibsovo for Acute Myelogenous Leukemia (AML) (AGIO) ............................................................................. 6

RHB-104 for Crohn's Disease (RDHL) ............................................................................................................. 6

Mogamulizumab for Cutaneous T-Cell Lymphoma (CTCL) - NHL (Kyowa Hakko Kirin) .................................. 7

Pixuvri for Diffuse Large B-Cell Lymphoma (DLBCL) - NHL (CTIC) .................................................................. 8

Elagolix for Endometriosis (ABBV) ................................................................................................................. 9

Humacyl for End-Stage Renal Disease (ESRD) (Humacyte) .......................................................................... 10

Galafold for Fabry's Disease (FOLD) ............................................................................................................ 11

AR101 for Food Allergies (AIMT) ................................................................................................................. 12

Lanadelumab for Hereditary Angioedema (HAE) (SHPG) ............................................................................ 13

Dasiglucagon for Hyperinsulinemia/Hypoglycemia (ZEAL) .......................................................................... 13

Eravacycline for Intra-Abdominal Infections (Antibacterial) (TTPH) ............................................................ 14

GS010 for Leber's Hereditary Optic Neuropathy (LHON) (Ophthalmology) (GenSight) .............................. 15

ELAD for Liver Failure / Cirrhosis (VTL) ........................................................................................................ 16

Emgality for Migraine and Other Headaches (LLY) ...................................................................................... 17

Azedra for Neuroendocrine Tumors (NET) (PGNX) ...................................................................................... 19

Dacomitinib for Non-Small Cell Lung Cancer (NSCLC) (PFE) ........................................................................ 20

Lorlatinib for Non-Small Cell Lung Cancer (NSCLC) (PFE) ............................................................................ 21

Tonmya for Post-Traumatic Stress Disorder (PTSD) (TNXP) ........................................................................ 22

Arikayce for Respiratory Tract Infections (Excluding Pneumonia) (Antibacterial) (INSM) ........................... 23

Tpoxx for Smallpox (SIGA) ........................................................................................................................... 23

Lusutrombopag for Thrombocytopenia (Shionogi) ..................................................................................... 24

Ulipristal Acetate for Uterine Fibroids (AGN) .............................................................................................. 25

EGP-437 for Uveitis (Ophthalmology) (EYEG) .............................................................................................. 26

Q3 2018 Large Impact Drug Catalysts……………..…..………………..…………………………………………………………………28

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Outcomes of Biomedtracker's Large Impact Catalysts from the Q2 2018 Outlook Report

Occurred Date

Lead Company Product Market Catalyst Did LOA Predict

Outcome

LOA Before Outcome

LOA After Outcome

4/9/2018 AbbVie Upadacitinib Autoimmune/ immunology

Phase III SELECT-COMPARE - Top-Line Results

Yes 67%

(8% Above Avg.) 68%

(9% Above Avg.)

4/23/2018 Prothena NEOD001 Metabolic Phase Iib PRONTO - Top-Line

Results No

64% (2% Above Avg.)

0% (Same as Avg.)

4/26/2018 Alexion ALXN1210 Autoimmune/ immunology

Phase III SWITCH Study - Top-Line Results

Yes 65%

(6% Above Avg.) 69%

(10% Above Avg.)

5/10/2018 Akcea Waylivra Endocrine FDA Advisory Panel Meeting No 82%

(3% Below Avg.) 86%

(1% Above Avg.)

5/17/2018 Amgen Aimovig Neurology PDUFA for BLA - First Review Yes 93%

(10% Above Avg.) 100%

(Same as Avg.)

5/21/2018 Dova Doptelet Hematology PDUFA for NDA - First Review Yes 85%

(1% Above Avg.) 100%

(Same As Avg.)

5/24/2018 BioMarin Palynziq Metabolic PDUFA for BLA - First Review Yes 96%


(Same as Avg.)

5/29/2018 Novo Nordisk Oral Semaglutide Endocrine Phase III PIONEER 2 - Top-Line

Results Yes

67% (7% Above Avg.)

72% (12% Above Avg.)

5/31/2018 Eli Lilly Olumiant Autoimmune/ immunology

PDUFA for NDA - Second Review Yes 90%


(Same as Avg.)

6/5/2018 AbbVie Upadacitinib Autoimmune/ immunology

Phase III SELECT-EARLY - Top-Line Results

Yes 68%

(9% Above Avg.) 70%

(11% Above Avg.)


Results / Phase III PIONEER 7 - Top-Line Results

Yes 72%


(14% Above Avg.)

6/21/2018 Incyte Jakafi Autoimmune/ immunology

Phase II REACH-1 - Top-Line Results N/A 59%

(Same as Avg.) 62%

(3% Above Avg.)

6/25/2018 Achaogen Zemdri Infectious disease PDUFA for NDA - First Review Yes1 98%

(10% Above Avg.) 100%

(Same as Avg.)

6/25/2018 Achaogen Zemdri Infectious disease PDUFA for NDA - First Review Yes2 73%

(15% Below Avg.) 45%

(16% Below Avg.)

6/25/2018 GW Epidiolex Neurology PDUFA for NDA - First Review Yes 99%

(16% Above Avg.) 100%

(Same As Avg.)

July 2018 / 5


6/27/2018 Array Braftovi Oncology PDUFA for NDA - First Review Yes 90%


(Same as Avg.)

6/27/2018 Array Mektovi Oncology PDUFA for NDA - First Review Yes 83%


(Same As Avg.)

6/27/2018 Cara Korsuva Neurology Phase III CLIN-3001 - Top-Line

Results Yes

59% (7% Above Avg.)

60% (8% Above Avg.)


Results Yes



7/2/2018 Roche Tecentriq Oncology Phase III IMpassion 130 - Top-Line

Results Yes

40% (5% Above Avg.)

43% (8% Above Avg.)

1For Urinary Tract and Reproductive Tract Infections (Antibacterial)

2For Septicemia or Bacteremia (Antibacterial, including Endocarditis)

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Tibsovo for Acute Myelogenous Leukemia (AML) (AGIO)

Drug Company Partner(s) Indication(s) Date Range Expected

Catalyst(s)

Tibsovo Agios

Pharmaceuticals, Inc. N/A

Acute Myelogenous Leukemia (AML)

08/21/2018 PDUFA for NDA - First

Review (R/R AML)

Phase Disease Group Drug Class Group/Class

Phase Success Group/Class

LOA (PTS) BMT LOA Opinion

NDA Oncology NME 84.42% 85.00% Above

Ivosidenib, a small-molecule inhibitor of isocitrate dehydrogenase 1 (IDH1), has a PDUFA date of August 21. An approval would bring the first targeted treatment to relapsed or refractory AML patients who havean IDH1 mutation. The mutant enzyme IDH1 is found in various tumour types, including gliomas,sarcomas and haematological malignancies such as AML. Although IDH1 mutations are estimated to occurin only 6–10% of AML patients, they are associated with poor disease prognosis. Clinical data supportingthe application demonstrate an overall response rate of 41.6%, with durable remission rates (30.4% ofpatients had a complete remission or complete remission with haematological recovery, including 21.6%who had a complete remission), as well as favourable transfusion independence rates that were achievedacross multiple response categories. These results validate the benefit of targeting IDH1, establishingivosidenib as part of a wave of new, targeted therapies for the treatment of AML. For the 8–19% of AMLpatients who carry IDH2 mutations, Agios has already introduced a new treatment paradigm with theIDH2 inhibitor enasidenib (Idhifa), which was approved by the FDA last year. Both drugs highlight thecompany’s rapidly developed portfolio of compounds that target cancer cell metabolism. Furthermore,Agios is developing AG-881, an orally available, potent inhibitor of both IDH1 and IDH2, currently in PhaseI testing for glioma. Datamonitor Healthcare is forecasting sales of ivosidenib for AML across the US,Japan and five major EU markets will reach $86 million by 2025.

RHB-104 for Crohn's Disease (RDHL)


Catalyst(s)

RHB-104 RedHill Biopharma Ltd. N/A Crohn's Disease 08/01/2018-08/31/2018

Phase III MAP US - Top-Line Results




III Autoimmune/immunology Non-NME 65.63% 54.21% Average

RHB-104 is an oral antibiotic combination therapy containing rifabutin, clarithromycin and clofazimine, for the potential treatment of Mycobacterium avium subspecies paratuberculosis (MAP) infection, which may be a disease-promoting factor in Crohn's disease. RedHill Biopharma is currently assessing the safety and efficacy of RHB-104 in a Phase III study in moderate to severely active Crohn’s Disease. The Phase III MAP US is a randomized, double blind, placebo-controlled study in U.S., Canada, Europe, Israel, Australia

https://www.biomedtracker.com/catalystdetail.cfm?CatID=139072

https://service.datamonitorhealthcare.com/hkc/disease/oncology/leukemia/acute-myeloid-leukemia/forecast/article175419.ece

https://www.biomedtracker.com/catalystdetail.cfm?catid=136623

July 2018 / 7


and New Zealand. The primary endpoint is disease remission, defined as Crohn's Disease Activity Index (CDAI) value of less than 150 at week 26.

An independent data and safety monitoring board (DSMB) conducted two pre-planned analyses reviewing the safety and efficacy of RHB-104 in the Phase III MAP US study. In 2016, RedHill Biopharma announced that the DSMB conducted its first safety review and unanimously recommended the continuation of the Phase III study. Furthermore, the second DSMB review in 2017, analyzing safety and efficacy data of the first 222 subjects who had completed week 26 assessments, also resulted in a unanimous positive recommendation from the independent review committee. Blinded efficacy data suggest a total number of treatment of successes consistent within the predefined expected treatment outcome and reveal a blended remission rate consistent with or superior to pre-specified protocol assumptions. RedHill Biopharma is expected to report unblinded top-line results from the Phase III MAP US study in August 2018.

RedHill Biopharma anticipates that additional clinical studies will need to be conducted to support a New Drug Application submission for RHB-104 in the United States. However, if the upcoming MAP US study results are positive, RedHill plans to present the data package to the U.S. Food and Drug Administration to obtain guidance on the best path forward to support marketing approval. To supplement the upcoming Phase III data, RedHill initiated the MAP US2 study, an open-label extension to assess the effects of RHB-104 in patients who completed the Phase III MAP US study and remain with active Crohn’s disease (CDAI>150) at week 26. Together, results from these two trials may serve as supportive clinical data for potential future marketing applications.

Mogamulizumab for Cutaneous T-Cell Lymphoma (CTCL) - NHL (Kyowa Hakko Kirin)


Catalyst(s)

Mogamulizumab Kyowa Hakko Kirin Co., Ltd.

N/A Cutaneous T-Cell

Lymphoma (CTCL) - NHL 09/04/2018

PDUFA for BLA - First Review




BLA Oncology Biologic 94.59% 85.00% Above

In November 2017, Kyowa Hakko Kirin announced that the U.S. Food and Drug Administration (FDA) accepted the Biologics License Application (BLA) for mogamulizumab to treat Cutaneous T-cell Lymphoma (CTCL) in patients who have received at least one prior systemic therapy, and that the application was granted Priority Review status. Mogamulizumab is a humanized monoclonal antibody targeting CCR4, a chemokine receptor selectively expressed in T-helper type 2 cells and regulatory T cells and frequently present on the surface of CTCL cells. During the review, Kyowa Hakko Kirin submitted additional documentation related to the manufacturing section of the BLA and the FDA decided that it constituted a major amendment requiring a 3-month extension to the original target action date. As a result, the Prescription Drug User Fee Act (PDUFA) target action date has been extended to September 4, 2018.



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This BLA is supported by data from the MAVORIC (Mogamulizumab anti-CCR4 Antibody Versus ComparatOR In CTCL) study, a global randomized trial evaluating the efficacy and safety of mogamulizumab in patients with relapsed/refractory CTCL. The trial enrolled mycosis fungoides patients (the most common form of CTCL) as well as Sezary syndrome patients. The primary objective of the study was progression free survival. Mogamulizumab was first approved in Japan in 2012 for relapsed or refractory CCR4-positive adult T-cell leukemia-lymphoma (ATL) and in 2014 for use in chemotherapy-naive CCR4-positive ATL and relapsed or refractory CCR4-positive peripheral T-cell lymphoma (PTCL) and CTCL.

In December 2017, Kyowa Hakko Kirin released the full dataset of the study and highlighted the significantly better PFS for the mogamulizumab group compared to the control (vorinostat) group. The median PFS was 7.7 months for the mogamulizumab arm and 3.1 months for vorinostat arm (p<0.0001). Global ORR was also significantly improved in the patients randomized to mogamulizumab at 28.0% vs 4.8% for vorinostat (p<0.0001). Patient-reported outcomes, as measured by the Skindex-29 and FACT-G, showed significantly greater symptom reduction and improved functional status in favor of mogamulizumab vs vorinostat (p<0.05). Based on data from this study, the US FDA granted Breakthrough Therapy Designation to mogamulizumab for the treatment of Mycosis Fungoides (MF) and Sézary Syndrome (SS) in adult patients who have received at least one prior systemic therapy.

Seattle Genetics’ Adcetris was approved in November 2017 for CD30-expressing CTCL patients with mycosis fungoides who have received prior systemic therapy. In a Phase III pivotal trial, PFS was 15.8 months for patients treated with Adcetris vs 3.6 months for patients receiving physician’s choice therapy. This 15.8 months PFS is substantially better than the 7.7 months PFS seen with mogamulizumab and will likely give Adcetris a competitive advantage. However, mogamulizumab may be approved for a wider group of patients as the MAVORIC trial enrolled mycosis fungoides patients as well as Sezary syndrome patients. Finally, CCR4 expression level was not an eligibility criterion for the MAVORIC trial while Adcetris is approved only for CD30-expressing CTCL patients. If approved, mogamulizumab will be a first in class option for CTCL, an orphan disease with an unmet medical need.

Pixuvri for Diffuse Large B-Cell Lymphoma (DLBCL) - NHL (CTIC)


Catalyst(s)

Pixuvri CTI BioPharma

Corporation Servier, Clinigen

Diffuse Large B-Cell Lymphoma (DLBCL) - NHL

07/01/2018-09/30/2018

Phase III - PIX-R Top-line Data




III Oncology NME 43.08% 36.28% Below

Pixuvri (pixantrone), in development by CTI BioPharma (CTIC), is an aza-anthracenedione analogue of Novantrone (mitoxantrone) developed to correct the cardiotoxicity seen with Novantrone. Like other anthracyclines, pixantrone inhibits topo-isomerase II. However, pixantrone alkylates (rather than intercalates) DNA, forming stable DNA adducts with specificity for CpG-rich, hyper-methlyated sites.


July 2018 / 9


Pixantrone is being developed as a potential treatment for patients with aggressive B-cell or grade 3 follicular non-Hodgkin lymphoma (NHL).

CTI is currently conducting the Phase III PIX306 trial comparing pixantrone combined with rituximab to gemcitabine combined with rituximab. The trial enrolled patients who had failed front line CHOP-R and were not eligible for autologous stem cell transplant (ASCT) (2nd line) or had failed ASCT (3rd or 4th line). Top-line results from PIX306 are expected in the third quarter of 2018.

Pixantrone has previously been granted conditional marketing authorization from the European Commission as monotherapy for the treatment of adult patients with multiply relapsed or refractory aggressive B-cell NHL. PIX306 is being conducted as a post-authorization requirement of conditional marketing authorization. If positive, the results from this trial could support broader indications both in the EU and the US, despite past failures at gaining approval.

Elagolix for Endometriosis (ABBV)


Catalyst(s)

Elagolix AbbVie Inc. Neurocrine Endometriosis 08/06/2018 PDUFA for NDA -

First Review




NDA Obstetrics/Gynecology NME 100.00% 83.00% Above

Elagolix is an investigational, orally administered gonadotropin-releasing hormone (GnRH) antagonist, being evaluated for the management of endometriosis with associated pain. Elagolix was originally developed by Neurocrine Biosciences, and in June 2010, Abbvie and Neurocrine entered a collaboration agreement to develop and commercialize Elagolix for the treatment of endometriosis-related pain. In addition to endometriosis, Elagolix is being evaluated for the treatment of uterine fibroids and benign prostatic hyperplasia (BPH).

On September 6th, 2017, Abbvie and Neurocrine Biosciences announced they submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for Elagolix for the treatment of endometriosis. The NDA is supported by data from the prospective randomized endometriosis clinical trials conducted to date, which evaluated the safety and efficacy of Elagolix in nearly 1,700 women with moderate-to-severe endometriosis-associated pain. The data from two replicate Phase III studies demonstrated that, at month three and month six, both Elagolix doses (150 mg once daily and 200 mg twice daily) resulted in a statistically significant higher proportion of responders for reduced menstrual pain (dysmenorrhea) and reduced non-menstrual pelvic pain associated with endometriosis as measured by the Daily Endometriosis Pain Impact scale versus placebo.

Elagolix has a safety profile consistent with the partial hormone suppression associated with its mechanism of action. Safety findings were consistent across Phase III trials and showed reduced rates of amenorrhea (lack of menstruation) and reduced bone density loss (at the lower dose) compared to GnRH


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agonists. Though Elagolix has positive efficacy results and a better safety profile compared to existing GnRH agonists, the Companies received notification by the FDA that it required extended time to review the results of liver function tests provided by AbbVie. The Prescription Drug User Fee Act (PDUFA) date has been extended three months, even though Elagolix received priority review from the FDA. Despite the review extension from the FDA, Elagolix, with its positive safety profile, has the potential to be the first approved drug for the treatment of endometriosis in over ten years.

Humacyl for End-Stage Renal Disease (ESRD) (Humacyte)


Catalyst(s)

Humacyl Humacyte, Inc. N/A End-Stage Renal Disease (ESRD)

07/01/2018-09/30/2018

Phase III HUMANITY - Top-Line Results




III Renal Biologic N/A N/A Average

Humacyte expects to report top-line data from its Phase III HUMANITY study of Humacyl for hemodialysis access in patients with end-stage renal disease during the third quarter of 2018. Humacyl are human acellular vessels (HAVs) that are created from donated human muscle cells placed on a tubular scaffold made of biodegradable suture material. The tissue cells grow in vitro to form a biologic 3D scaffold matrix. The cells are then removed from the HAV matrix and once implanted, the HAV may be remodeled by the patient to create a vascular structure more similar to native, adjacent vascular tissue.

This method of creating a biological graft is to reduce the rate of failure as compared to plastic dialysis grafts, which can have complications of infection, thrombosis, and hyperplasia and saves the need to use the patient’s own blood vessels to serve as a surrogate in the plastic graft. Due to the possible benefits provided by this treatment, the U.S. Food and Drug Administration (FDA) provided the program with Fast Track designation on July 2014 and Regenerative Medicine Advanced Therapy (RMAT) designation on March 2017.

In May 2016, Humacyte announced published results from Phase II studies of Humacyl. 60 patients were implanted and at 6 months, 63% of patients had primary patency, 73% had primary assisted patency, and 97% had secondary patency, with most loss of primary patency because of thrombosis. At 12 months, 28% had primary patency, 38% had primary assisted patency, and 89% had secondary patency. One vessel became infected during 82 patient-years of follow-up. The vessels had no dilatation and rarely had post-cannulation bleeding. Based on the positive results, Humacyte launched the Phase III HUMANITY study of Humacyl as a conduit for hemodialysis in patients with End-Stage Renal Disease (ESRD) requiring renal replacement therapy and who are not candidates for fistula.

In the trial, Humacyl will be compared to expanded polytetrafluoroethylene (ePTFE) grafts, standard of care for ESRD patients who require hemodialysis but are not suitable for creation of an autologous arteriovenous (AV) fistula. The primary objective of this Phase III, 350-patients study will be to compare the secondary patency of the HAV with that of the ePTFE graft when used as a conduit for hemodialysis. If


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the top-line data expected in the third quarter are positive, Humacyte plans to file a BLA to seek approval of Humacyl.

Galafold for Fabry's Disease (FOLD)


Catalyst(s)

Galafold Amicus

Therapeutics, Inc. GlaxoSmithKline Fabry's Disease 08/13/2018

PDUFA for NDA - First Review




NDA Metabolic NME 64.71% 75.00% Above

The FDA will decide on the NDA for accelerated approval of migalastat on August 13. Migalastat is intended to treat Fabry disease in patients 16 years or older who have amenable genetic mutations. This rare genetic disease is caused by deficiency of the α-galactosidase A enzyme, which degrades specific lipids in lysosomes that would otherwise accumulate and cause irreversible organ damage. Migalastat is designed as a chaperone therapy to stabilize certain mutant enzymes to facilitate normal trafficking to lysosomes, thereby reducing lysosomal substrate accumulation. In addition to this unique mechanism, migalastat is available orally, which is an advantage over the established enzyme replacement therapy (ERT) Fabrazyme (agalsidase alfa, marketed by Sanofi), the only Fabry disease treatment to be approved by the FDA since 2003.

Migalastat is already approved in the European Union, Japan and other markets, including Australia and Canada. Interestingly, the FDA had previously wanted another study to confirm a clinical benefit, such as on GI symptoms, but then apparently changed their minds after the company submitted new analyses, as well as data on cardiac and renal effects, longer term extension data, and the experience of patients taking the commercial drug in Europe, especially those switched from ERT. Of note, the company has not received notice of an advisory committee and will likely not need one, since it is past the time when the FDA seeks to give notification, which is probably a positive sign for the drug. If approved, migalastat is anticipated to have a strong market impact in the United States, and Amicus expects its migalastat global revenue from 2017 to double this year.

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