Biomed Tracker

5/21/2018 Biomed Tracker

1/30

f

BioMedTracker

Early 2014OUTLOOK

REPORT

W W W . B I O M E D T R A C K E R . C O M
http://www.biomedtracker.com/http://www.biomedtracker.com/http://www.biomedtracker.com/


2/30

Early 2014 BioMedTracker Outlook Report

QUESTIONS? [email protected]

FOR OUR DISCLOSURES, PLEASE SEEBIOMEDTRACKERS RESEARCH STANDARDS

Summary

Our Q4 2013 Outlook Report highlighted several high-impact catalysts that resulted in large stock price

changes. The results of all of our Q4 catalysts can be found on Page 4 of this report. BioMedTracker

Likelihood of Approval (LOA) opinions successfully predicted 77% of catalyst outcomes in Q4 2013.

In this quarter's report, we cover catalysts from 25 drugs and 6 devices and have included a list of Large

Impact catalysts in the drug, device/diagnostic, and natural resource areas through April 2014 from our

sister product, CatalystTracker. In addition, each drugs likelihood of Phase/PDUFA review success and

overall Likelihood of Approval (LOA) given their particular phase, drug class, and disease group are

provided. Please note the current LOAs displayed on BioMedTracker are not based on these new

probabilities; these new data will be integrated at a later time.

If you would like a copy of the calendars in Excel, please emailBioMedTrackeror contact your sales

representative.

About the Author

BioMedTracker is an independent research service that offers proprietary clinical assessments and

patient-based revenue forecasts 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 the last several 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 2014 Sagient Research, Inc.

This report is published by Sagient Research, Inc. (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 Publisherwishes 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.
mailto:[email protected]:[email protected]:[email protected]://www.biomedtracker.com/standards.cfmhttp://www.biomedtracker.com/standards.cfmhttp://www.biomedtracker.com/standards.cfmmailto:[email protected]?subject=Early%202014%20Outlook%20Reportmailto:[email protected]?subject=Early%202014%20Outlook%20Reportmailto:[email protected]?subject=Early%202014%20Outlook%20Reportmailto:[email protected]:[email protected]:[email protected]:[email protected]?subject=Early%202014%20Outlook%20Reporthttp://www.biomedtracker.com/http://www.biomedtracker.com/standards.cfmmailto:[email protected]


3/30



FOR OUR DISCLOSURES, PLEASE SEEBIOMEDTRACKERS RESEARCH STANDARDS

Contents

Q4 Outlook Catalyst Results.. 4

VEN 307 for Chronic Pain (VTUS) ......................................................................................................... 6Vyvanse for Eating Disorders (SHPG) ................................................................................................... 7

Posidur for Postsurgical Pain (DRRX) ................................................................................................... 7

SB-728-T for HIV / AIDS (SGMO) .......................................................................................................... 8

PBT2 for Alzheimers Disease (PRAN) ................................................................................................... 9

PBT2 for Huntingtons Disease (PRAN) ................................................................................................. 9

Procysbi for Huntingtons Disease (RPTP) .......................................................................................... 10

MuDelta for Irritable Bowel Syndrome (IBS) (FURX) ........................................................................... 11

Imbruvica for Chronic Lymphocytic Leukemia (CLL)/Small Cell Lymphocytic Lymphoma (SLL) NHL

(PCYC) .............................................................................................................................................. 12

Rolapitant for Chemotherapy Induced Nausea and Vomiting (CINV) (TSRO) ....................................... 12

Naloxegol for Opioid Induced Constipation (AZN) .............................................................................. 13Estybon (intravenous) for Myelodysplastic Syndrome (MDS) (ONTX) .................................................. 14

Jakafi for Polycythemia Vera (PV) (INCY) ........................................................................................... 15

Otezla for Psoriatic Arthritis (CELG) ................................................................................................... 15

Vintafolide for Non-Small Cell Lung Cancer (NSCLC) (MRK) ................................................................. 16

LX4211 for Diabetes Mellitus, Type I (LXRX) ....................................................................................... 16

Vimizim for MPS IV (Morquio A Syndrome) (BMRN) .......................................................................... 17

RG7652 for Dyslipidemia/Hypercholesterolemia (Roche) ................................................................... 18

Bococizumab for Dyslipidemia/Hypercholesterolemia (PFE) ............................................................... 18

Alirocumab for Dyslipidemia/Hypercholesterolemia (REGN) .............................................................. 18

Evolocumab for Dyslipidemia/Hypercholesterolemia (AMGN) ........................................................... 19

BMS-962476 for Dyslipidemia/Hypercholesterolemia (BMY) .............................................................. 19

Northera for Orthostatic Hypotension (CHTP) .................................................................................... 21Eteplirsen for Muscular Dystrophy (SRPT) .......................................................................................... 22

Afrezza for Diabetes Mellitus, Type I and Type II (MNKD) ................................................................... 23

Dulaglutide for Diabetes Mellitus, Type II (LLY) .................................................................................. 24

Epi proColon for Diagnostics Colorectal Cancer (EPGNY) .................................................................. 25

Cologuard for Diagnostics Colorectal Cancer (EXAS) ........................................................................ 26

cobas HPV Test for Diagnostics Human Papillomavirus (HPV) (Roche) .............................................. 27

APPY1 for Diagnostics Appendicitis (APPY)...................................................................................... 28

illumigene Bordetella pertussis assay for Diagnostics Bordetella pertussis (VIVO) ............................ 29

Maestro Rechargeable System for Vagus Nerve Stimulation Devices Obesity (ETRM) ....................... 29

Early 2014 Large Impact Drug/Device/Natural Resource Catalyst Calendar...31
mailto:[email protected]:[email protected]:[email protected]://www.biomedtracker.com/standards.cfmhttp://www.biomedtracker.com/standards.cfmhttp://www.biomedtracker.com/standards.cfmhttp://www.biomedtracker.com/http://www.biomedtracker.com/standards.cfmmailto:[email protected]


4/30


QUESTIONS? [email protected] OUR DISCLOSURES, PLEASE SEEBIOMEDTRACKERS RESEARCH STANDARDS

4

Large Impact Catalysts from the BioMedTracker Q4 2013 Outlook Report

Occurred

DateLead Company Product Market Catalyst

Did LOA

Predict

Outcome

1-Day

Perf

1-Week

Perf

1-Month

Perf

12/11/2013 CytRx Corporation Aldoxorubicin SarcomaPhase IIb - Top Line

Results (PFS)Yes 156.07% 117.57% 212.55%

10/22/2013 Medivation Xtandi Prostate CancerPhase III PREVAIL -

Interim AnalysisN/A* 25.67% 28.26% 30.41%

11/14/2013 Vanda Tasimelteon Non-24 Hour DisorderFDA Advisory Panel

MeetingYes 11.89% -7.90% -17.94%

11/24/2013 Celldex Rindopepimut Brain Cancer (gliomas)Phase II ReACT

Top-Line Results at SNONo -9.75% -3.99% -18.62%

10/18/2013 Actelion OpsumitPulmonary Arterial

Hypertension

PDUFA for NDA - 1st

ReviewYes 7.98% 9.85% 16.50%

11/25/2013 CubistCeftolozane/

Tazobactam

UTI/Intra-abdominal

Infections

Phase III CXA-cUTI-10-04

Top-Line Results

N/A 4.98% 3.37% 2.20%


Tazobactam

UTI/Intra-abdominal

Infections

Phase III CXA-cUTI-10-05

Top-Line Results

N/A 4.98% 3.37% 2.20%


Tazobactam

UTI/Intra-abdominal

Infections

Phase III vs.

Meropenem

Top-Line Results

N/A 3.79% 6.13% 18.92%

11/19/2013 BioMarin Vimizim

Mucopolysaccharidosis

IV

(MPS IV; Morquio

Syndrome)

FDA Advisory Panel

MeetingYes 3.33% 5.41% 2.17%

10/25/2013 Gilead Sofosbuvir HCVFDA Advisory Panel

MeetingYes -1.58% 1.63% 6.83%

11/19/2013 Daiichi Sankyo EdoxabanStroke Prevention in

Atrial Fibrillation (SPAF)

Phase III ENGAGE AF-

TIMI 48 - Top-Line

Results at AHA

No -1.47% -4.09% -5.61%


5/30


QUESTIONS? [email protected] OUR DISCLOSURES, PLEASE SEEBIOMEDTRACKERS RESEARCH STANDARDS

5

Occurred

DateLead Company Product Market Catalyst

Did LOA

Predict

Outcome

1-Day

Perf

1-Week

Perf

1-Month

Perf

12/10/2013 Merck & Co. MK-8931 Alzheimer's DiseasePhase II/III - Interim

AnalysisYes -1.23% -3.35% 0.65%

11/3/2013 Merck & Co. MK-5172 HCVPhase II C-SPIRIT - Top-

Line Results at AASLDYes 1.08% 3.91% 10.02%

12/18/2013 GlaxoSmithKline Anoro Ellipta COPDPDUFA for NDA - First

ReviewYes 1.02% 2.57% 7.64%

11/1/2013 Roche Obinutuzumab CLLPDUFA for BLA - First

ReviewYes 0.72% -1.23% 0.59%

11/21/2013Forest

LaboratoriesCariprazine Schizophrenia

PDUFA for NDA - 1st

ReviewNo 0.31% -0.21% 13.13%

10/24/2013Johnson &

JohnsonSimeprevir HCV

FDA Advisory Panel

MeetingYes -0.01% 0.55% 3.83%

No previous LOA adjustment

*Xtandi LOA already approved and thus 100% LOA


6/30



FOR OUR DISCLOSURES, PLEASE SEEBIOMEDTRACKERs RESEARCH STANDARDS

VEN 307 for Chronic Pain (VTUS)

Drug Company Partner(s) Indication(s) Date RangeExpected

Catalyst(s)

VEN 307Ventrus Biosciences

(VTUS)

S.L.A Pharma

AG Chronic PainNow -

03/31/2014

Phase IIIb (US) - Top-

Line Results

Phase Disease Group Drug Class

Group/Class

Phase

Success

Group/Class

LOA (PTS)

BMT LOA

Opinion

III Neurology Non-NME 80.72% 68.91% Above

Ventruss VEN 307 (diltiazem cream) is a non-dihydropyridine calcium channel blocker that has been

used for the treatment of hypertension and angina. As diltiazem is approved as an oral formulation, VEN

307 is eligible for the FDAs 505(b)2 registration pathway. The diltiazem cream dilates blood vessels and

reduces anal sphincter tone, thereby substantially decreasing pain. VEN 307 is only minimally absorbed,

at one-tenth the amount of the lowest dose used for the cardiovascular treatment, and it significantlyreduces pain associated with anal fissures.

Currently in Phase III clinical development in the US, Ventrus previously released top-line data for its EU

Phase III study in which statistically significant improvements over placebo were seen for those treated

with VEN 307. In this EU study, the improvements in worst anal pain were statistically notable in week 4

(p=0.0134 for 2%, p=0.0108 for 4%) and in week 8 (p=0.0220 for 2%, p=0.0060 for 4%) in addition to the

improvements in overall daily anal fissure-related anal pain in the same time frame. Furthermore, a

very positive tolerability profile in both 2% and 4% dose strengths was reported.

Dermal irritation and pharmacokinetic Phase I studies were also conducted resulting in observations of

minimal adverse eventsnone of which were severe or serious. In the pharmacokinetic study, theparameters were consistent with expectations and prior data of approximately only a 10% systemic

exposure (versus the oral diltiazem) and high safety margins.

In this first quarter, Ventrus is expected to release the results of their US Phase IIIb study investigating

the use of 2% diltiazem cream in over 400 participants with anal fissures. Given the positive results in

the similar EU study and supplemental Phase I studies, VEN 307 is likely to be approved for the

treatment of pain associated with anal fissures with confirmatory data from the US Phase IIIb study.
mailto:[email protected]:[email protected]:[email protected]://www.biomedtracker.com/standards.cfmhttp://www.biomedtracker.com/standards.cfmhttp://www.biomedtracker.com/standards.cfmhttp://www.biomedtracker.com/DrugDetail.cfm?RecID=22889http://www.biomedtracker.com/DrugDetail.cfm?RecID=22889http://www.biomedtracker.com/DrugDetail.cfm?RecID=22889http://www.biomedtracker.com/http://www.biomedtracker.com/standards.cfmmailto:[email protected]


7/30




Vyvanse for Eating Disorders (SHPG)


Catalyst(s)

VyvanseShire Pharmaceuticals

(SHPG) ShionogiEating

Disorders

Now-

03/31/2014

Trial Data - Top-Line

Results

Phase Disease Group Drug ClassGroup/Class

Phase Success

Group/Class

LOA (PTS)

BMT LOA

Opinion

III Psychiatry NME 47.37% 35.53% Above

Vyvanse is an amphetamine prodrug, lisdexamfetamine dimesylat (LDX), in which lysine is linked to a d-

amphetamine single salt. The prodrug was designed to restrict the release of active pharmaceutical

ingredients from the compound to no more than therapeutically prescribed amounts. This formulation

limits the ability of abusers to obtain greater doses of the active ingredient through alternative routes of

administration or extraction techniques. Vyvanse was approved for the treatment of Attention Deficit

Hyperactivity Disorder (ADHD) in 2007, and as of November 2013, Shire has successfully completed two

pivotal Phase III trials for the treatment of binge eating disorder (BED).

Shire reported that their Vyvanse program is ahead of schedule and plans to report additional top-line

results for the Phase III study of Vyvanse for the treatment of BED in the first quarter of 2014. The study

is a pivotal, Phase III, open-label extension for patients who have completed one of the SPD489 BED

studies. While we do not anticipate issues with long-term safety signals, given Vyvanses chronic use in

ADHD, this study would provide more psychiatric data as there is likely a correlation between mood

changes and BED improvement. This psychiatric information may be important to projecting success in

the development of Vyvanse for Major Depressive Disorder (MDD) for which top-line results for the

Phase III trial are expected in the first half of 2014.

Posidur for Postsurgical Pain (DRRX)


Catalyst(s)

Posidur DURECT Corporation (DRRX) Postsurgical Pain 2/12/2014PDUFA for NDA

First Review


Phase Success

Group/Class

LOA (PTS)

BMT LOA

OpinionNDA Neurology Non-NME 85.37% 39.00% Below

DURECT announced that the New Drug Application (NDA) under the 505(b)2 pathway submitted for

POSIDUR (SABER-Bupivacaine) has been accepted by the U.S. Food and Drug Administration (FDA)

indicating that the application is sufficiently complete to permit a substantive review. The Prescription

Drug User Fee Act (PDUFA) goal date has been confirmed as February 12, 2014.
mailto:[email protected]:[email protected]:[email protected]://www.biomedtracker.com/standards.cfmhttp://www.biomedtracker.com/standards.cfmhttp://www.biomedtracker.com/standards.cfmhttp://www.biomedtracker.com/DrugDetail.cfm?RecID=24141http://www.biomedtracker.com/DrugDetail.cfm?RecID=24141http://www.biomedtracker.com/DrugDetail.cfm?RecID=10320http://www.biomedtracker.com/DrugDetail.cfm?RecID=10320http://www.biomedtracker.com/DrugDetail.cfm?RecID=10320http://www.biomedtracker.com/DrugDetail.cfm?RecID=24141http://www.biomedtracker.com/http://www.biomedtracker.com/standards.cfmmailto:[email protected]


8/30




Posidur is a long acting local anesthetic developed by DURECT for the treatment of postsurgical pain. It is

a subcutaneous injectable which is inserted near the surgical incision and it releases bupivacaine for a

period of 72 hours or more.

Posidur completed Phase IIb studies in hernia and shoulder surgery patients, which showed reduction in

pain and consumption of opioids versus placebo, the primary endpoints. The Phase III registrational trial,

BESST, studied Posidur in adult patients undergoing a variety of general abdominal surgical procedures.

Posidur was unable to show significantly decreased consumption of post-surgical opioids. The company

excused the drugs disappointing results by suggesting that the study was performed mostly in older

sicker patients. The one positive note from the BESST trial, was that the treatment resulted in a

significant reduction in movement pain versus the active comparator bupivacaine HCL.

After announcing these results, DURECT met with the FDA to discuss various chemistry, manufacturing,

non-clinical, clinical pharmacology, clinical, statistical, and product labeling topics prior to their NDA

submission. Despite failure to meet both co-primary endpoints in their registrational trial, the FDA could

be swayed to approve Posidur based on the pre-NDA discussion, and the positive Phase IIb results.

SB-728-T for HIV / AIDS (SGMO)


Catalyst(s)

SB-

728-T

Sangamo Biosciences

(SGMO)HIV/AIDS

Now

04/30/2014

Phase I/II 1002 - Top-Line

Results at International HIV

Persistence Workshop


Group/Class

Phase

Success

Group/Class

LOA (PTS)

BMT LOA

Opinion

II Infectious disease Biologic 33.33% 6.06% Above

SB-728-T is a CCR5-specific zinc finger protein nuclease utiilizing Sangamo's zinc finger DNA-binding

protein nuclease (ZFN) technology. CCR5 is a co-receptor that enables HIV to enter and infect cells of the

immune system.

Preclinical data demonstrated that a one-time exposure to CCR5-specific ZFNs resulted in the generation

of an HIV-resistant population of human primary T-cells by the permanent genetic modification of the

CCR5 gene. These ZFN-modified CD4 T-cells expanded stably in HIV-infected cultures for several weeks

and appeared to behave identically to untreated T-cells except that they were resistant to infection by

HIV. ZFN treated primary CD4 T-cells and transformed CD4 cell lines resisted infection with R5-tropic HIV

(virus that uses the CCR5 co-receptor to enter cells), resulting in enrichment of ZFN-generated CCR5-

disrupted cells in the population upon long-term exposure to virus (>50 days).

Data from a Phase II extension study showed, of the six evaluable subjects, two subjects were observed

in which their viral load (VL) became undetectable during treatment interruption (TI) from antiretroviral

therapy (ART). In one subject, VL suppression at, or below, the limit of quantification (LOQ) of virus was

sustained from week 11 19 of TI and at the time of analysis, the TI was ongoing. In the second subject

there was a transient suppression of VL at or below LOQ. The subject remains off ART. A third subject


9/30




completed the TI with 1-log decrease in VL from peak. In three subjects, there was no reduction in VL

during the TI, one completed the TI and in two the TI was terminated early due to their viral loads

exceeding the upper limit allowed in the protocol. A seventh subject had yet to complete TI and was still

being evaluated. The data demonstrate functional control of the virus at or below the limit of detection

in CCR5 delta-32 heterozygote HIV-infected subjects treated with SB-728-T.

Data from the 1002 Single Dose Phase I/II clinical trial of SB-728-T in subjects with HIV are expected in

early 2014. The study completed patient enrollment in October 2011 and enrolled 21 subjects who are

not on antiretroviral therapy who have a CD4 T cell count that is greater than 500 cells per millimeter

cubed and a measurable viral load in their peripheral blood.

PBT2 for Alzheimers Disease (PRAN)


Catalyst(s)

PBT-2 Prana Biotechnology(PRAN)

Alzheimer'sDisease (AD)

03/01/2014-03/31/2014

Phase IIa IMAGINE -Top-Line Results


Phase Success

Group/Class

LOA (PTS)

BMT LOA

Opinion

II Neurology NME 26.12% 10.21% Below

PBT2 for Huntingtons Disease (PRAN)

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

Expected

Catalyst(s)

PBT-2Prana Biotechnology

(PRAN)

Huntington's

Disease

Now -

03/31/2014

Phase II - Top-Line

Results


Phase Success

Group/Class

LOA (PTS)

BMT LOA

Opinion

II Neurology NME 26.12% 10.21% Below

Top line data from two Phase II studies evaluating Pranas lead metal-protein attenuating compound,

PBT-2, for Alzheimers and Huntingtons disease are anticipated this quarter. As discussed in ourQ4

2013 Outlook Report,Reach2HD results were anticipated in October 2013 but they were subsequentlydelayed. These first results will indicate whether further development in HD is warranted.

A previous 12-week Phase II study in early-stage AD resulted in marginal improvements in cognition and

reductions in amyloid beta. The current study, IMAGINE, is measuring the effect of PBT-2 compared to

placebo on amyloid levels at 52 weeks in patients with early or mild AD. Cognition is being evaluated as

a secondary endpoint. It will be interesting to see whether a longer treatment period and patients with

more advanced disease results in greater effects on either endpoint.
mailto:[email protected]:[email protected]:[email protected]://www.biomedtracker.com/standards.cfmhttp://www.biomedtracker.com/standards.cfmhttp://www.biomedtracker.com/standards.cfmhttp://www.biomedtracker.com/DrugDetail.cfm?RecID=1921http://www.biomedtracker.com/DrugDetail.cfm?RecID=1921http://www.biomedtracker.com/DrugDetail.cfm?RecID=23701http://www.biomedtracker.com/DrugDetail.cfm?RecID=23701http://www.biomedtracker.com/ReportDetail.cfm?ReportID=384http://www.biomedtracker.com/ReportDetail.cfm?ReportID=384http://www.biomedtracker.com/ReportDetail.cfm?ReportID=384http://www.biomedtracker.com/ReportDetail.cfm?ReportID=384http://www.biomedtracker.com/ReportDetail.cfm?ReportID=384http://www.biomedtracker.com/ReportDetail.cfm?ReportID=384http://www.biomedtracker.com/DrugDetail.cfm?RecID=23701http://www.biomedtracker.com/DrugDetail.cfm?RecID=1921http://www.biomedtracker.com/http://www.biomedtracker.com/standards.cfmmailto:[email protected]


10/30




We previously discussed PBT-2 efficacy with the co-founder of Prana Biotechnology and while he

defended efficacy results: The original paper in 08 in Lancet Neurology didnt have significance because

Quintiles made a mistake on the math as a CRO, then they had published an erratum in 2009. It really

hurt the company showing that the z-score was significant for the overall NPB and was driven by

executive function z-score,we continue to be skeptical of the metal theory in AD as well as HD. The KOLbelieves the dark horse mechanism of this disease is that Abeta aggregation and toxicity requires

copper binding and in fact if you look at Huntingtons it is the same thing, with alpha synuclein its iron.

Reactive metals binding to abnormally folded proteins trigger free radical production.

While we agree that free radical production and reactive oxygen species generation is a critical step in

the neurogenerative process, there still exists a dearth of knowledge regarding the relationship of

protein folding and the role of metal ions in AD and HD pathology. Particularly, there is little information

in regards to specific location, isolated form, and role of metal accumulation in these diseases. Based on

the currently unimpressive data in AD and concern regarding this non-targeted approach to bind metal

ions, we do not have high expectations for the AD or HD trials.

The full interview is available on KOL Insight.

Procysbi for Huntingtons Disease (RPTP)


Catalyst(s)

Procysbi

Raptor

Pharmaceutical

(RPTP)

Huntington's

Disease

Now-

03/31/2014

Phase II/III - Top Line

Results


Phase Success

Group/Class

LOA (PTS)

BMT LOA

Opinion

II/III Neurology Non-NME 80.72% 68.91% Average

RP103 (Procysbi), a delayed-release formulation of cysteamine, is in Phase II/III development as a

potential treatment for Huntingtons disease. The compound received U.S. approval in April 2013 to

treat nephropathic cystinosis and is also in Phase II development for pediatric non-alcoholic fatty liver

disease.

The ongoing Phase II/III study is evaluating treatment with RP103 over 36 months an initial 18 month,double blind, placebo controlled period, followed by an 18-month open label period during which all

patients receive RP103. The study is being conducted in 96 patients in France. Data on the primary

endpoint, Total Motor Score of the Unified Huntingtons Disease Rating Scale, during the first 18 months

of treatment are anticipated this quarter. If the data are positive, this bodes well for HD patients as

there are no currently approved disease-modifying therapies.


11/30




MuDelta for Irritable Bowel Syndrome (IBS) (FURX)


Catalyst(s)

MuDeltaFuriex

Pharmaceuticals

(FURX)

Johnson

&

Johnson

(JNJ)

Irritable Bowel

Syndrome (IBS)Now -02/28/2014

Phase III Study 3001

Top-Line Results

Phase III Study 3002

Top-Line Results

Phase Disease GroupDrug

Class

Group/Class

Phase Success

Group/Class

LOA (PTS)

BMT LOA

Opinion

III

Gastroenterology

(non-

inflammatory

bowel disease)

NME 66.67% 61.11% Average

Furiex is developing MuDelta (eluxadoline), an oral mu opioid receptor agonist and delta opioid receptorantagonist, for the treatment of diarrhea-predominant irritable bowel syndrome (IBS-D). The cause of

IBS-D is unknown and may differ between subgroups of patients. Symptoms vary by patient but often

include chronic abdominal pain and frequent diarrhea. The dual opioid activity of eluxadoline is

designed to treat these symptoms, without the constipating side effects associated with mu opioid

agonists. In June 2012, Furiex initiated two Phase III trials comparing eluxadoline (75 or 100 mg BID) to

placebo in IBS-D patients. Top-line data from both studies are expected to be released in February.

Encouraging results were observed in a Phase II trial in 807 patients. The primary endpoint was clinical

response at week 4, defined by mean changes in pain intensity and stool consistency. Patients receiving

25 and 200 mg BID of eluxadoline met the primary endpoint compared to placebo (p


12/30




Imbruvica for Chronic Lymphocytic Leukemia (CLL)/Small Cell Lymphocytic Lymphoma (SLL) NHL

(PCYC)


Catalyst(s)

ImbruvicaPharmacyclics

(PCYC)

Johnson & Johnson

(JNJ)CLL/SLL 2/28/2014

PDUFA for NDA - First

Review


Group/Class

Phase

Success

Group/Class

LOA (PTS)

BMT LOA

Opinion

NDA Oncology NME 77.32% 76.00% Above

Imbruvica is a covalent, small molecule inhibitor of Bruton's tyrosine kinase (BTK), which is required for

early B-cell maturation. On June 28, 2013, Pharmacyclics submitted a New Drug Application (NDA) to the

U.S. Food and Drug Administration (FDA) for Imbruvica for two B-cell malignancy indications in the

relapsed/refractory setting: mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL)/smalllymphocytic lymphoma (SLL). The NDA received priority review status on August 27, 2013.

Imbruvica has demonstrated efficacy as a monotherapy in previously-treated CLL patients, and it carries

a benign safety profile compared to cytotoxic chemotherapy agents of particular importance due to

the high median age and presence of co-morbidities of CLL patients. In the Phase III RESONATE trial,

Imbruvica showed statistically significant improvements in progression-free survival and overall survival

compared to treatment with ofatumumab; the RESONATE independent data monitoring board halted

the trial early due to the magnitude of difference between the arms. On November 11, 2013, the FDA

announced that it had approved Imbruvica for the treatment of MCL but had not made a final decision

for the CLL indication. We expect an FDA approval for Imbruvica in CLL by the PDUFA date of February

28, 2014.

Rolapitant for Chemotherapy Induced Nausea and Vomiting (CINV) (TSRO)


Catalyst(s)

Rolapitant Tesaro (TSRO)Opko Health

(OPK)

Chemotherapy Induced

Nausea and Vomiting

(CINV)

Now-

04/30/2014

Phase III HEC1 -

Top-Line Results


Phase Success

Group/Class

LOA (PTS)

BMT LOA

Opinion

III Oncology NME 44.06% 34.07% Below

Rolapitant is a Neurokinin-1 (NK1) receptor antagonist for the treatment of chemotherapy-induced

nausea and vomiting (CINV). Rolapitant and other long-acting NK1 antagonists play a pivotal role in

suppressing delayed onset (24120 h after chemotherapy) nausea and vomiting, though they also play a

role in the acute phase (024 h). Tesaro's rolapitant is a potential alternative to the Merck's NK1

antagonist Emend (aprepitant/fosaprepitant). The rolapitant Phase III development program includes
mailto:[email protected]:[email protected]:[email protected]://www.biomedtracker.com/standards.cfmhttp://www.biomedtracker.com/standards.cfmhttp://www.biomedtracker.com/standards.cfmhttp://www.biomedtracker.com/DrugDetail.cfm?RecID=21157http://www.biomedtracker.com/DrugDetail.cfm?RecID=21157http://www.biomedtracker.com/DrugDetail.cfm?RecID=21157http://www.biomedtracker.com/DrugDetail.cfm?RecID=20386http://www.biomedtracker.com/DrugDetail.cfm?RecID=20386http://www.biomedtracker.com/DrugDetail.cfm?RecID=20386http://www.biomedtracker.com/DrugDetail.cfm?RecID=21157http://www.biomedtracker.com/DrugDetail.cfm?RecID=21157http://www.biomedtracker.com/http://www.biomedtracker.com/standards.cfmmailto:[email protected]


13/30




two identical trials enrolling patients receiving highly-emetogenic chemotherapy (HEC1 and HEC2) and

one trial for patients receiving moderately-emetogenic chemotherapy (MEC). Top-line results for the

HEC1 trial of rolapitant are expected in early 2014.

In Tesaro's Phase III HEC2 and MEC trials of standard of care plus rolapitant or placebo, rolapitant met

its primary endpoint of an increased rate of complete response for delayed phase CINV. However, the

difference in complete response rate was not statistically significant between treatment arms in the

acute phase and overall (two secondary endpoints). Previously presented results for a Phase II

study (HEC patients) showed significant improvements in complete response for all three endpoints

(acute phase, delayed phase, overall) for patients receiving 200 mg of rolapitant. As these larger Phase

III trials were similarly designed, it is unclear why these trials did not succeed. However, failure to

achieve significance in acute-phase CINV has also been observed in the Phase II data of Helsinn

Healthcares NEPA, a netupitant/palonosetron FDC, which is currently under review by the FDA.

Results of Tesaros final Phase III trial HEC1 are critical for the success of rolapitant, as the approved

Emend is effective at preventing both acute and delayed CINV. A failure in HEC1 may require Tesaro to

reconsider its rolapitant development plan or shift resources towards its niraparib clinical program.

Naloxegol for Opioid Induced Constipation (AZN)


Catalyst(s)

Naloxegol AstraZeneca (AZN)Nektar

(NKTR)

Opioid Induced

Constipation

3/10/14

3/11/14

FDA Advisory

Panel Meeting


Phase Success

Group/Class

LOA (PTS)

BMT LOA

Opinion

NDA

Gastroenterology

(non- inflammatory

bowel disease)

NME 91.67% 33.00% Above

AstraZenecas naloxegol (NKTR-118) is a PEGylated version of a naloxone analog that binds to all three

opioid receptors (mu, kappa, and gamma). The company filed a new drug application (NDA) for

naloxegol for opioid-induced constipation (OIC) in adult patients with chronic non-cancer pain with the

U.S. Food and Drug Administration (FDA) in September 2013, with an anticipated PDUFA date of

September 16, 2014.

AstraZenecas filing was based on data from the Phase III KODIAC program, which included four clinical

trials investigating the safety and efficacy of naloxegol for the treatment of OIC in patients with non-

cancer related pain. Results of the studies were positive, as patients receiving the 25 mg/day dosage

demonstrated a statistically significant improvement in responder rate (a measure of spontaneous

bowel movement frequency, the primary endpoint) vs. placebo in the KODIAC-04 and -05 efficacy

studies. A non-significant trend in efficacy was observed in patients receiving 12.5 mg/day; therefore,

we anticipate that the sponsors will seek approval for the 25 mg/day dose. Naloxegol appeared to be

generally safe and well-tolerated over the treatment period with the most commonly reported adverse

events (AEs) being gastrointestinal (GI)-related. No imbalance in CV events was noted between
mailto:[email protected]:[email protected]:[email protected]://www.biomedtracker.com/standards.cfmhttp://www.biomedtracker.com/standards.cfmhttp://www.biomedtracker.com/standards.cfmhttp://www.biomedtracker.com/DrugDetail.cfm?RecID=6457http://www.biomedtracker.com/DrugDetail.cfm?RecID=6457http://www.biomedtracker.com/http://www.biomedtracker.com/standards.cfmmailto:[email protected]


14/30




treatment and placebo groups, and patients receiving naloxegol did not have significant changes in pain

scores or opioid use.

The Anesthetic and Analgesic Drug Products Committee is tentatively scheduled to meet on March 10

11, 2014 to discuss drugs for OIC, including naloxegol and the Salix drug Relistor. The briefing documents

for the advisory panel meeting are expected one to two business days prior to the meeting.

Estybon (intravenous) for Myelodysplastic Syndrome (MDS) (ONTX)


Catalyst(s)

Estybon

(intravenous)

Onconova

Therapeutics

(ONTX)

Baxter (BAX);

SymBio

Myelodysplastic

Syndrome

Now -

03/31/2014

Phase III

ONTIME Top-

Line Results

Phase Disease Group Drug Class Group/ClassPhase Success

Group/ClassLOA (PTS)

BMT LOAOpinion

III Oncology NME 44.06% 34.07% Average

Estybon (intravenous) is a multi-kinase inhibitor of targets associated with malignancy, including the

polo-like kinase (PLK-1) and PI3 kinase/AKT pathways. Estybon causes cell cycle arrest and apoptosis of

cancer cells. Estybon (intravenous) is Onconova's first drug to reach Phase III development, with a focus

on treatment in refractory/relapsed, higher-risk MDS patients. We expect Onconova to announce top-

line results from its Phase III ONTIME study in the first quarter of 2014.

Results from a Phase I/II study (04-15) in AML and higher-risk MDS patients showed that 53% of patients

(n=19) demonstrated a reduction or stabilization in bone marrow blasts or improvement in peripheralblood counts. These responders had a higher median overall survival compared to patients who had no

response (9.6 months vs. 1.7 months, p=0.001), suggesting a correlation between hematological

response and survival benefit. MDS patients had a better median overall survival than AML patients (15

months vs. 2 months), leading Onconova to focus on MDS patients in its Phase III program. Phase II trials

of an oral formulation of Estybon are also underway in patients with lower-risk MDS.

The pivotal ONTIME study was given a Special Protocol Assessment (SPA) by the US Food and Drug

Administration (FDA) in October 2010. In this study, higher-risk MDS patients relapsed/refractory or

intolerant to hypomethylating agents receive a continuous IV pump of Estybon for 72 hours every other

week for 16 weeks, then every 4 weeks afterwards. The primary endpoint for ONTIME is overall survival

at 18 months. If top-line results from this study are positive, Onconova could file for marketing approval

in the US and EU as soon as the second half of 2014.


15/30




Jakafi for Polycythemia Vera (PV) (INCY)

In 2011, Jakafi (ruxolitinib) became the first FDA approved therapy for myelofibrosis (MF), including

secondary MF following polycythemia vera (PV) or essential thromobcythemia (ET). Now, Jakafi is on

track to also become the first approved targeted therapy for PV with top-line results from the pivotal

Phase III - RESPONSE trial expected in between March 2014 and April 2014.

Early data from a Phase II trial were positive with a robust 100% response rate (62% CR, 38% PR) in PVpatients refractory or intolerant to hydroxyurea (HU). Importantly, patients achieved normalized blood

cell counts and decreases in other disease symptoms such as spleen size and pruritus. There were few

drug-related toxicities which is critical considering the potential long-term treatment of this chronic

condition. (It should be noted that lower response rates were observed in the ET patients in the same

study, and development for ET has since been suspended.)

Positive results from RESPONSE should solidify Jakafi as the leading JAK inhibitor for myeloproliferative

disorders, although other JAK inhibitors are in development including momelotinib (GILD) and pacritinib

(CTIC), both already in Phase III trials for MF.

Otezla for Psoriatic Arthritis (CELG)


Catalyst(s)

Otezla Celgene (CELG)Psoriatic

Arthritis3/21/2014

PDUFA for NDA First

Review (Psoriatic Arthritis)


Phase Success

Group/Class

LOA (PTS)

BMT LOA

Opinion

NDA Autoimmune/immunology NME 66.67% 55.00% Above

Otezla (apremilast) is a small molecule inhibitor of phosphodiesterase 4 (PDE4), a novel target for

arthritic diseases, that is on track to become the first targeted oral therapy for psoriatic arthritis.

Celgene submitted a NDA to the FDA in March 2013 for Otezla (apremilast) for the treatment of adult

patients with active psoriatic arthritis, and a PDUFA decision is anticipated on March 21, 2014.

The submission is based on the PALACE 1-3 studies which have posted uniformly positive data to date.

Positive data have also been reported from the PALACE 4 study in treatment-nave patients, but that


Catalyst(s)

Jakafi

Incyte Corporation

(INCY)

Novartis AG

(NVS)

Polycythemia

Vera (PV)

03/01/2014-

04/30/2014

Phase III RESPONSE -

Top-Line Results


Phase Success

Group/Class

LOA (PTS)

BMT LOA

Opinion

III Hematology NME 72.22% 60.51% Above


16/30




study was most likely excluded from the current regulatory filing. A MAA regulatory submission in

Europe was also recently filed.

If approved, Psoriatic Arthritis will be the first approved indication for Otezla and could be launched in

the second-half of 2014. An approval for psoriasis should follow shortly with an approval decision

anticipated in 3Q2014.

Vintafolide for Non-Small Cell Lung Cancer (NSCLC) (MRK)


Catalyst(s)

VintafolideMerck & Co.

(MRK)

Endocyte

(ECYT)NSCLC

Now -

03/31/2014

Phase IIb TARGET - Top-

Line Data


Group/Class

PhaseSuccess

Group/Class

LOA (PTS)

BMT LOA

Opinion

IIb Oncology NME 25.29% 8.62% Below

Vintafolide is essentially a novel chemotherapy (a conjugate of folate and vinca alkaloid) in development

for several solid tumors. In NSCLC, top-line data are expected from the Phase IIb TARGET study in the

first quarter of 2014 and will provide the first evidence of a path forward in that indication.

A previously completed Phase II study suggested stronger efficacy in patients with tumors expressing

the folate receptor [FR(++)]. Thus, the TARGET study was designed to enroll patients in that narrower

population. Recently, however, the DSMB interim analysis recommended that the monotherapy arm

would be unlikely to show superiority over the docetaxel arm for PFS. Given the generally similarmechanisms, perhaps it should not have been too surprising that vintafolide did not appear to be

showing superiority over docetaxel, even if vintafolide is active. Now the concern is whether its activity

will really be additive on top of docetaxel in the continuing combination therapy arm, and

BioMedTracker is maintaining a 2% below average likelihood of approval.

LX4211 for Diabetes Mellitus, Type I (LXRX)


Catalyst(s)

LX4211Lexicon

Pharmaceuticals

(LXRX)

Diabetes Mellitus,

Type INow-03/31/2014

Phase II - Top-line

Results


Class

Group/Class

Phase Success

Group/Class

LOA (PTS)

BMT LOA

Opinion

II Endocrine NME 30.50% 12.80% Average


17/30




LX4211 is an orally administered dual inhibitor of sodium glucose transporters 1 and 2 (SGLT1 and

SGLT2) in development for diabetes. Inhibition of SGLT2 is an established mechanism for reducing

hyperglycemia through the kidney in diabetes patients. LX4211 differentiates from other SGLT2

inhibitors with its additional affinity for SGLT1 in the small intestine. There is some evidence that this

increases GLP-1 levels. This theoretically would contribute to even lower glucose absorption, but based

on the Phase IIb data n Type II diabetes, it is not clear that LX4211 is really more effective or will have

fewer GU infections, a side effect of this class (please see our 2013 post-ADAreport).

In type 2 diabetes, Lexicon has been waiting to secure a partnership before embarking on Phase III. So in

terms of data, focus has shifted to the ongoing Phase II proof-of-concept study in type 1 diabetes, an

area in which an oral small molecule has not yet been approved.

Lexicon anticipates reporting top-line data from the Phase II study at the end of this quarter. The study

began in early 2013 and has enrolled 30 type 1 diabetics. Results from the study will validate whether

the dual mechanism is also beneficial for these patients and help advance LX4211 into later stage trials.

Other oral SGLT-2 inhibitors being evaluated for type 1 diabetes include empagliflozin (Boehringer/LLY)

and dapagliflozin (BMY/AZN), both of which are currently in Phase II development. While the SGLT-2

mechanism does appear to work in type 1 diabetes, it is somewhat unclear how much a benefit it will beto patients who have to take intensive insulin.

Vimizim for MPS IV (Morquio A Syndrome) (BMRN)


Catalyst(s)

VimizimBioMarin

(BMRN)

Mucopolysaccharidosis

IV02/28/2014

PDUFA for BLA - First

Review


Phase Success

Group/Class

LOA (PTS)

BMT LOA

Opinion

BLA Metabolic Biologic 75% 62% Above

BioMarin is developing Vimizim as a treatment for mucopolysaccharaidosis IV, also known as Morquio A

Syndrome, an orphan inherited disease of metabolism that causes abnormal development in children.

The regulatory application for Vimizim was submitted to the FDA in April 2013 and was granted priority.

On November 19, an FDA advisory committee voted as follows: 19 for approval for all MPS IV patients, 1

for approval in a subset, and 1 against approval. A sizeable minority of panelists actually felt the drug

only appeared to be effective in a subgroup of patients with worse baseline walking ability, but most

wanted it approved overall, so the long-term effects in various subgroups could be followed, forexample via a patient registry. Hence, we think it is likely it will be approved for the overall population,

though information about the differential effectiveness could appear on the label. The FDA is expected

to make an approval decision on Vimizim by February 28, 2014.
mailto:[email protected]:[email protected]:[email protected]://www.biomedtracker.com/standards.cfmhttp://www.biomedtracker.com/standards.cfmhttp://www.biomedtracker.com/standards.cfmhttp://www.biomedtracker.com/ReportDetail.cfm?ReportID=378http://www.biomedtracker.com/ReportDetail.cfm?ReportID=378http://www.biomedtracker.com/ReportDetail.cfm?ReportID=378http://www.biomedtracker.com/DrugDetail.cfm?RecID=18739http://www.biomedtracker.com/DrugDetail.cfm?RecID=18739http://www.biomedtracker.com/DrugDetail.cfm?RecID=18739http://www.biomedtracker.com/ReportDetail.cfm?ReportID=378http://www.biomedtracker.com/http://www.biomedtracker.com/standards.cfmmailto:[email protected]


18/30




RG7652 for Dyslipidemia/Hypercholesterolemia (Roche)


Catalyst(s)

RG7652 Roche Chugai Dyslipidemia /Hypercholesterolemia

Now-03/31/14

Phase II - EQUATORTop-Line Results


Phase Success

Group/Class

LOA (PTS)

BMT LOA

Opinion

II Cardiovascular Biologic 35.29% N/A Average

Bococizumab for Dyslipidemia/Hypercholesterolemia (PFE)


Catalyst(s)

Bococizumab Pfizer (PFE)Dyslipidemia /

Hypercholesterolemia03/30/2014

Phase IIb

Subcutaneous

(B1481015 Top-Line

Data at ACC


Phase Success

Group/Class

LOA (PTS)

BMT LOA

Opinion

III Cardiovascular Biologic 18.18% N/A Average

Alirocumab for Dyslipidemia/Hypercholesterolemia (REGN)


Catalyst(s)

AlirocumabRegeneron

(REGN)

Sanofi

(SNY)

Dyslipidemia /


Data at

ACC


Phase Success

Group/Class

LOA (PTS)

BMT LOA

Opinion

III Cardiovascular Biologic 18.18% N/A Above


19/30




Evolocumab for Dyslipidemia/Hypercholesterolemia (AMGN)


Catalyst(s)

EvolocumabAmgen

(AMGN)Astellas

Dyslipidemia /


Data at

ACC


Phase Success

Group/Class

LOA (PTS)

BMT LOA

Opinion

III Cardiovascular Biologic 18.18% N/A Above

BMS-962476 for Dyslipidemia/Hypercholesterolemia (BMY)


Catalyst(s)

BMS-

962476

Bristol-Myers Squibb

(BMY)

Dyslipidemia /


Data at

ACC


Phase Success

Group/Class

LOA (PTS)

BMT LOA

Opinion

I Cardiovascular Biologic 75% N/A Average

Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) inhibitors are an experimental class of cholesterol

lowering drugs which have shown outstanding success in reducing LDL-c in Phase I and II trials.

Evolocumab (Amgen) and Alirocumab (Regeneron) are the furthest along in development with Phase III

starting to be released. RN316 (Pfizer) is not far behind in development, having started Phase III about a

year later. However, its cardiovascular outcomes study is smaller than the other two and currently is

slated to complete earlier, though timing can depend on interim analyses. Roches RG7642 and Lillys

LY3015014 are currently in Phase II development.

Since the drugs are biologics given via subcutaneous injection, they will primarily be used in higher risk

patients who do not reach LDL reduction goal on oral medications (those with CV disease or equivalent

risk, as well as familial hypercholesterolemia) and patients who are statin intolerant.

While Evolocumab has completed a number of Phase III trials over the past year (GAUSS-2, LAPLACE-2,

MENDEL-2, DESCARTES, and RUTHERFORD), Amgen has only reported that results are consistent with

their previous Phase II studies. These studies involve a broad range of patients, including heterozygous

familial hypercholesterolemia and statin intolerance, among others, as well as long-term treatment.
mailto:[email protected]:[email protected]:[email protected]://www.biomedtracker.com/standards.cfmhttp://www.biomedtracker.com/standards.cfmhttp://www.biomedtracker.com/standards.cfmhttp://www.biomedtracker.com/DrugDetail.cfm?RecID=20637http://www.biomedtracker.com/DrugDetail.cfm?RecID=26626http://www.biomedtracker.com/DrugDetail.cfm?RecID=26626http://www.biomedtracker.com/DrugDetail.cfm?RecID=20637http://www.biomedtracker.com/http://www.biomedtracker.com/standards.cfmmailto:[email protected]


20/30




Details from these studies are slated to be presented at the upcoming American College of Cardiology

(ACC) meeting in March.

Evolocumab's Phase II studies showed LDL-c reductions in the range of 48-55% from baseline for the

monthly dose and 51-66% for the every other week dose. However, there were only a couple major

Phase II studies with this dosing, the one Alirocumab is focusing on, so it will be interesting to see more

results on this from the Phase III program. It will also be interesting to see if there are any details on

monthly versus every other week dosing, since the monthly dosing in Phase II appeared to lead to

appreciable swings in LDL-c levels. For comparison, Alirocumab has reported data from one Phase III trial

with every other week dosing, showing a 47.2% reduction in LDL-C.

A total of 5 abstracts for Alirocumab have been selected for presentation at the ACC meeting, including

24-week Phase III data (likely the ODYSSEY Mono study) and one year open-label treatment data with

150 mg every other week in HeFH patients. There will also be data from what appears to be Phase I

study with monthly dosing either alone or in combination with ezetimibe or fenofibrate. Alirocumab's

Crestor add-on study in patients at high cardiovascular risk is slated for primary completion in February,

so top-line data could come within a few months, and other Phase III data is expected mid-year.

A major competitive feature among the PCSK9 inhibitors is convenience of delivery. Alirocumab will be

delivered in a 1 ml autoinjector. Amgen has not disclosed the volume of injection for Evolocumab, but

the every other week dosage is likely to be given via autoinjector, as well. They just recently disclosed a

study for the large-volume monthly dose, where LDL-c reductions were similar for some type of mini-

doser or 3 injections via an autoinjector. These do not sound particularly convenient.

Bococizumab will have top-line data from its subcutaneous Phase IIb trial at the ACC. This will be

especially important, because prior Phase II data involved IV dosing. The Phase IIb trial involves monthly

and every other week dosing, so it will be interesting to see if its monthly doses have any advantages

over what was seen with Evolocumab in Phase II. One researcher at a past conference noted that the

maximum concentration for these drugs may be around 150 mg/ml, and Bocozicumab is using 200 mgand 300 mg in its monthly dose. Hence, it will also be interesting to see if there is any more information

on what type of delivery device it may be able to use, since it is possible that 2 ml could be given via an

auto-injector.

Roches RG7652 has yet to read out efficacy data. The Phase II EQUATOR study, completed in September

2013, compared RG7652 to placebo in 248 patients with coronary heart disease or high risk of coronary

heart disease. While the company has previously stated that they do not plan to move the compound

into Phase III development by themselves, citing only intellectual property issues, it will be useful to

see how the monthly dosing results compare to others. The company has said in the past that results

from this trial could potentially be presented at the ACC conference, but we are not seeing it on the

schedule.

Finally, BMS-962476, an adnectin targeting PCSK9, will have its first data, which will be from a Phase I

single ascending dose study. Adnectins are smaller than antibodies and cheaper to manufacture, though

they tend to have a shorter half-life, so it will be interesting to see if there are modifications extending

the half-life.


21/30




Northera for Orthostatic Hypotension (CHTP)


Catalyst(s)

Northera

Chelsea

Therapeutics(CHTP)

Dainippon

SumitomoPharma

OrthostaticHypotension 02/13/2014 PDUFA for NDA -Second Review


Class

Group/Class

Phase Success

Group/Class

LOA (PTS)

BMT LOA

Opinion

NDA Cardiovascular NME 73.33% 60% Above

Northera (Droxidopa , L-Threo-3,4-dihydroxyphenylserine) is an orally active synthetic precursor of

norepinephrine (NE). It stimulates receptors for vasoconstriction via the peripheral nervous system.

Nothera is intendedfor the treatment of symptomatic neurogenic orthostatic hypotension (known as

Neurogenic OH or NOH) in patients with primary autonomic failure (Parkinson's disease, multiple system

atrophy and pure autonomic failure), dopamine beta hydroxylase deficiency and non-diabetic

autonomic neuropathy.

In March 2012, due to questions about efficacy, Northera received a Complete Response Letter after its

first PDUFA review, despite a 7-4 advisory committee vote in favor of approval. The FDA felt the vote

was really more split, since an abstaining and an absent member would likely have voted negatively.

Chelsea responded to the FDAs Complete Response Letter in July of 2013, with data from an additional

study. The FDA, however, had issues with that study, and had also raised questions about a foreign site

from the first major study with a number of super-responders. Nevertheless, in January 2014, given the

high unmet need in the indication, an advisory committee voted 16 to 1 that Northera should be

granted approval. The vote for Northera, was much more favorable than at the last meeting, which

should convince the FDA to approve the drug this go round. Some of the panelists were only in favor ofapproving it short term, for example 1-2 weeks, but others argued against that. We doubt the FDA

would limit it in this way, though given the lack of durability, there may be wording that the drug was

only shown to have a short term benefit. A number of panel members also mentioned they thought the

approval should be an accelerated one, where the sponsor has to show a positive post-marketing study

to stay on the market. An FDA official noted they had included language in that regulation to allow for

such situations, where a short term benefit was shown and a longer term benefit must be confirmed. It

is likely the FDA will use that type of approval.


22/30




Eteplirsen for Muscular Dystrophy (SRPT)


Catalyst(s)

Eteplirsen

Sarepta

Therapeutics

(SRPT)

University

ofWestern

Australia

MuscularDystrophy

Now 03/31/2014

Meeting with FDAConfirmatory Stud


Class

Group/Class

Phase Success

Group/Class

LOA (PTS)

BMT LOA

Opinion

II Metabolic NME 34.88% 13.46% Above

Sarepta Therapeutics anticipates meeting with the FDA to discuss different clinical endpoints, combined

endpoints, and different DMD subpopulations in order to finalize the confirmatory study of eteplirsen

for the treatment of Duchenne muscular dystrophy (DMD) in the first quarter of 2014. If accepted by the

FDA, the finalized confirmatory study design would enable Sarepta to begin dosing patients in the trial

beginning in the second quarter of 2014. Eteplirsen is a phosphorodiamidate morpholino oligomer(PMO) designed to induce the skipping of exon 51 in the dystrophin gene. Morpholino oligomers are an

antisense technology used to block access of other molecules to specific sequences within nucleic acid.

Inducing the skipping of exon 51 of the dystrophin gene restores the open reading frame for these

specific mutations to make a shorter but working form of the protein, theoretically benefitting patients

with certain deletion mutations in the dystrophin gene.

Sarepta had plans to submit an New Drug Application (NDA) on the limited Phase II data that had

already been seen for eteplirsen, but in November 2013, citing a failed study with drisapersen and

recent natural history data in DMD, the FDA indicated the new data raise "considerable doubt" about

both the dystrophin biomarker and the clinical efficacy assessed on the 6-minute walk test (6MWT) in

the Phase IIb clinical study of eteplirsen. That study was quite small, and patients received placebo foronly a limited period. The FDA believes that a larger placebo controlled trial would be best, and because

the 6MWT excludes certain age groups, limiting enrollment, raised the possibility of other endpoints.

These issues will likely come up in a meeting with the FDA on the design of a confirmatory study and

leave Sarepta with uncertainty over the feasibility of a trial. Nevertheless, we think it is likely an

agreement could be made to further advance the development of eteplirsen for a condition with an

unmet medical need like DMD. The outcome of this discussion will certainly help provide a clearer

picture for the next steps Sarepta has to take in order to advance eteplirsen into a pivotal confirmatory

study in the second quarter, for which positive results would likely enable a regulatory filing for

approval.
mailto:[email protected]:[email protected]:[email protected]://www.biomedtracker.com/standards.cfmhttp://www.biomedtracker.com/standards.cfmhttp://www.biomedtracker.com/standards.cfmhttp://www.biomedtracker.com/DrugDetail.cfm?RecID=12186http://www.biomedtracker.com/DrugDetail.cfm?RecID=12186http://www.biomedtracker.com/http://www.biomedtracker.com/standards.cfmmailto:[email protected]


23/30




Afrezza for Diabetes Mellitus, Type IandType II (MNKD)


Catalyst(s)

Afrezza

MannKind

Corporation(MNKD)

Diabetes, Type Iand Type II 04/01/2014 FDA Advisory PaneMeeting


Class

Group/Class

Phase Success

Group/Class

LOA (PTS)

BMT LOA

Opinion

NDA Endocrine Non-NME 94.44% 90% Below

The Endocrinologic and Metabolic Drugs Advisory Committee of the U.S. Food and Drug Administration

(FDA) is tentatively scheduled on April 1, 2014 to review MannKind's New Drug Application (NDA) for

Afrezza (insulin human [rDNA origin]) Inhalation Powder. Afrezza is a dry powder formulation of insulin

administered using the companys Dreamboat inhaler. MannKind resubmitted the NDA on October 13,

2013 seeking approval to market Afrezza in the United States with an indication to improve glycemic

control in adults with type 1 or type 2 diabetes mellitus. Afrezza, as an inhaled insulin, could help those

in the diabetes community that might have a negative perception of injected insulin.

MannKind originally submitted a New Drug Application (NDA) in March 2009, but received a Complete

Response Letter (CRL) in March 2010 requesting more information on the clinical utility of the drug,

updated safety data, and labeling changes regarding its MedTone inhaler for Afrezza. MannKind

resubmitted the NDA using its second generation Dreamboat inhaler to the FDA in June 2010 and

received a second CRL in January 2011. The principal issue raised by the FDA concerned the usage of in

vitro performance data and clinical pharmacology data to bridge MannKind's next-generation inhaler to

the Phase III trials conducted using its MedTone inhaler, which then required two additional trials with

the new inhaler.

In August 2013, Mannkind released data from their trials evaluating Afrezzas Dreamboat inhaler needed

for resubmission in both type 2 and type 1 diabetes. Study 175 (type 2 diabetes) and Study 171 (type 1

diabetes) both met their primary endpoints, but pending more details, questions still remain on that

being enough to approve Afrezza in both type 1 and type 2 diabetes. Study 175 only showed modest

efficacy but with an appreciable increase in hypoglycemia. Study 171 was positive on its primary

endpoint of non-inferiority and lowered hypoglycemia, though it also performed numerically slightly

worse than the injectable insulin comparator on efficacy, which could have helped the hypoglycemia.

While it met its major goal of showing that lung function declines with the Dreamboat inhaler were not

worse than that seen with the MedTone one, the larger pulmonary decline with Dreamboat seen in

Study 175 in type 2 diabetes could raise concern with the FDA. The Endocrinologic and Metabolic Drugs

Advisory Committee is set to meet in early April to discuss these concerns and make a recommendationon the approvability of Afrezza, and the briefing information released in the days prior to the meeting

should help shed more light on the situation.


24/30




Dulaglutide for Diabetes Mellitus, Type II (LLY)


Catalyst(s)

Dulaglutide Eli Lilly (LLY)Diabetes Mellitus,

Type II

Now

04/30/2014

Phase III AWARD-6 Top

Line Results


Phase Success

Group/Class

LOA (PTS)

BMT LOA

Opinion

NDA Endocrine NME 70.37% 52% Above

Dulaglutide is a once-weekly GLP-1 agonist. Data from the AWARD-6 trial, comparing it to the current

market leader, daily Victoza, is expected to come in a press release during the first quarter of 2014. The

first comparison will be whether the 1.5 milligram dose is non-inferior to Victoza with a non-inferiority

margin of 0.4%. If that is met, they will move to a superiority analysis.

As we noted in our 2013 post-ADAreport,because of the variability in trials, it is difficult to say how

dulaglutide would stack up directly against Victoza. For example, in head-to-head trials with Byetta,

Victoza had a 0.3% advantage and Bydureon a 0.4-0.7% advantage, yet in a head-to-head trial of

Bydureon versus Victoza (DURATION-6), Victoza had a 0.2% statistically significant advantage. For

comparison, dulaglutide had a 0.5% advantage over Byetta.

Interestingly, in AWARD-3, dulaglutide 1.5 mg showed superiority in A1c over metformin, whereas

Bydureon had similar efficacy as metformin in DURATION-4, though some of that could be due to a

somewhat lower maximum dose of metformin used in the dulaglutide study.

Given the direct comparison against the market leader, the study is an important one for defining

dulaglutide's attributes. Overall, we tend to think that dulaglutide will not perform worse than Bydureondid against Victoza, and it could well perform comparably to Victoza. Understandably, the company has

said they are not expecting superiority, and demonstrating that would be somewhat of an upside

surprise for the drug. But it will be important to see that it does not also have more nausea, a common

side effect with these agents. Early on in AWARD-1, dulaglutide had numerically worse rates of nausea

than Byetta, whereas Victoza in its trial against Byetta had similar rates. It will also be important to see

that weight loss with dulaglutide does not lag substantially.

Even if dulaglutide performs slightly worse on A1c than Victoza, it could still do well in the market, given

its more convenient dosing schedule. Still, it may only split the market with Victoza, even if it is of similar

efficacy, given the latter's established position. (Please see our 2013 post-ADAreportfor physician

opinions.)
mailto:[email protected]:[email protected]:[email protected]://www.biomedtracker.com/standards.cfmhttp://www.biomedtracker.com/standards.cfmhttp://www.biomedtracker.com/standards.cfmhttp://www.biomedtracker.com/DrugDetail.cfm?RecID=12378http://www.biomedtracker.com/DrugDetail.cfm?RecID=12378http://www.biomedtracker.com/ReportDetail.cfm?ReportID=378http://www.biomedtracker.com/ReportDetail.cfm?ReportID=378http://www.biomedtracker.com/ReportDetail.cfm?ReportID=378http://www.biomedtracker.com/ReportDetail.cfm?ReportID=378http://www.biomedtracker.com/ReportDetail.cfm?ReportID=378http://www.biomedtracker.com/ReportDetail.cfm?ReportID=378http://www.biomedtracker.com/ReportDetail.cfm?ReportID=378http://www.biomedtracker.com/ReportDetail.cfm?ReportID=378http://www.biomedtracker.com/DrugDetail.cfm?RecID=12378http://www.biomedtracker.com/http://www.biomedtracker.com/standards.cfmmailto:[email protected]


25/30




Epi proColon for Diagnostics Colorectal Cancer (EPGNY)

Company Partner(s) Project Market(s) Date RangeExpected

Catalyst(s)

Epigenomics

(EPGNY)

Epi

proColon

Diagnostics -

Colorectal Cancer

3/25/2014FDA Advisory

Committee Meeting

Colorectal cancer is the second leading cause of cancer deaths in the United States and the leading

cause of cancer deaths for nonsmokers. It can take up to 10-15 years for colorectal cancer to progress

from pre-cancerous lesion to metastatic cancer and death. Because colorectal cancer has a high rate of

survivability when diagnosed early, the American Cancer Society currently recommends that all people

over the age of 50 undergo regular colorectal cancer screenings. Sixty percent of colorectal cancer cases

are diagnosed in later stages, and it is estimated that up to one in two U.S. citizens are not up to date

with recommended colonoscopy or fecal occult blood test screenings. Since the standard of care for

colorectal cancer screening is the invasive colonoscopy, there is an unmet need for less invasive

screening tests. The following two products are designed to meet that need through non-invasive

testing.

Epigenomics AG is a molecular diagnostic company developing and commercializing products for the

screening and diagnosis of cancer. Epi proColon is a qualitative in vitrodiagnostic test for the detection

of aberrantly methylated Septin9 (SEPT9) DNA in plasma derived from patient blood specimens. The

methylated SEPT9 gene is found in colorectal cancer but not in the healthy colon. According to

Epigenomics, 62 percent of patients refused a colonoscopy but 87 percent opted for a blood based

colorectal diagnostic test. The high rate of adherence to a blood based test could be very beneficial for

Epigenomics top-line growth. Epi proColon takes eight hours to return a result and requires minimal

training for lab personnel, which could allow for easier integration within medical facilities.

In October 2011, Epigenomics announced the European launch of its second generation blood test for

colorectal cancer screening, Epi proColon 2.0. In a head-to-head comparison study between EpiproColon and FIT (Fecal Immunochemical Testing), Epi proColon demonstrated an overall specificity of

82% (December 2012). The study included subjects who were average risk, asymptomatic screening

patients and with no family history of colorectal cancer. In the final analysis of study results, Epi

proColon was able to detect 74% of all evaluable colorectal cancer cases in comparison to 67% of

colorectal cases detected by FIT.

Epigenomics AG announced a meeting with the Molecular and Clinical Genetics Panel of the Medical

Advisory Committee is scheduled to take place on March 25, 2014. If Epigenomics receives a favorable

panel vote, it could pave the way for FDA approval. If Epi proColon is approved, Epigenomics could be an

ideal growth stock if it is able to successfully convert a low compliance colorectal cancer screening

market by providing a blood based cancer screening test that has a higher rate of adherence.
mailto:[email protected]:[email protected]:[email protected]://www.biomedtracker.com/standards.cfmhttp://www.biomedtracker.com/standards.cfmhttp://www.biomedtracker.com/standards.cfmhttp://www.catalysttracker.com/ProductReport.cfm?ProductID=22320http://www.catalysttracker.com/ProductReport.cfm?ProductID=22320http://www.catalysttracker.com/ProductReport.cfm?ProductID=22320http://www.biomedtracker.com/http://www.biomedtracker.com/standards.cfmmailto:[email protected]


26/30




Cologuard for Diagnostics Colorectal Cancer (EXAS)

Company Partner(s) Project Market(s) Date RangeExpected

Catalyst(s)

Exact Sciences

(EXAS)

CologuardDiagnostics - Colorectal

Cancer

3/26/2014FDA Advisory Committee

Meeting

Exact Sciences (EXAS) is a molecular diagnostic company focused on the early detection and prevention

of colorectal cancer. EXAS developed a non-invasive diagnostic test for the early detection of colorectal

cancer. The Cologuard test is a non-invasive, stool-based DNA screening test designed to detect DNA

markers that are associated with colorectal cancer. The test also includes a protein marker to detect

blood in the stool utilizing an antibody-based fecal immunochemical test (FIT). Cologuard allows the

patient to collect a stool sample using EXAS collection apparatus and mail the stool sample to a

designated laboratory. The company has acknowledged that Cologuard will not replace the colonoscopy

procedure because polyps that are detected can be removed during a colonoscopy, but rather their

market focus is the patient who opts not to undergo a colonoscopy for personal reasons.

On April 18, 2013, EXAS announced top-line results for a 10,000 patient trial that demonstrated 92

percent sensitivity in the detection of colorectal cancer and 42 percent sensitivity for the detection of

pre-cancerous polyps. The test achieved a specificity of 87 percent, but the 42 percent sensitivity for

pre-cancerous polyp detection fell below EXAS 50 percent internal target. Study detection results fell

below market expectations, with investors anticipating a specificity of closer to 90 percent, and EXAS

common shares lost over 11 percent on the announcement. EXAS acknowledged that Cologuards ability

to detect pre-cancerous lesions fell below expectations but reaffirmed that Cologuard would be viewed

as effective by doctors and insurers. EXAS did not test trial patients stools over treatment intervals, but

anticipate that in the real world, screening would take place once every few years and the slow growth

of polyps would give physicians enough time to detect polyps. EXAS believes that in theory this would

create a sensitivity of 90 percent. Cologuard was not designed to be more accurate than a colonoscopy,

but rather as a less invasive option that will lead to higher colon cancer screening rates. The studyresults were used as part of a June 7, 2013 PMA submission for FDA approval. On March 26, 2014, an

FDA Advisory Panel Meeting will be held to review the PMA submission, and if the meeting returns

favorable results, the EXAS Cologuard product could be approved. EXAS has had an interactive dialogue

with the FDA and plans to be open in discussing the trial results with the panel members.

For the year ended December 31, 2012, EXAS reported licensing revenues of $4.1 million and an

operating loss of $56.642 million. If Cologuard is approved, the test will cost several hundred dollars and

EXAS currently estimates that U.S. market potential to be around $2 billion while the global market is

greater than $3 billion (assuming a 30 percent test adoption rate and a three year screening inte

Biomed Tracker

Documents

Transcript of Biomed Tracker