Enanta Pharmaceuticals Inc (ENTA)

[NY1972]

EXPEDITION-1 started

A Single Arm, Open-label Study to Evaluate the Efficacy and Safety of ABT-493/ABT-530 in Adults With Chronic Hepatitis C Virus Genotype 1, 2, 4, 5 or 6 Infection and Compensated Cirrhosis (EXPEDITION-1)

ABT-493/ABT-530 for 12 weeks

Estimated Enrollment: 175
Study Start Date: December 2015
Estimated Study Completion Date: November 2016
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)

[NY1972]

Very expensive data to go with the $350 million voucher. Patients must be lining up for this trial, free $1000 pill + DCV/day for 12 weeks.

[DewDiligence]

Did FDA request this?

Probably not, IMO. Most phase-3 HCV trials use a control arm consisting of the same regimen with a delayed start (to enable a safety comparison vs placebo).

[NY1972]

Did FDA request this?
Will MRK P3 triple combo go head-to-head against Sofosbuvir (SOF) and Velpatasvir (VEL) in GT3 patients?

[DewDiligence]

Going head-to-head against Solvaldi + Daklinza in GT3 patients is a gutsy move.

[NY1972]

ENDURANCE 2,3 started

A Randomized, Double-Blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of ABT-493/ABT-530 in Adults With Chronic Hepatitis C Virus Genotype 2 Infection (ENDURANCE-2)

ABT-493/ABT-530 for 12 weeks
Placebo for ABT-493/ABT-530 for 12 weeks followed by ABT-493/ABT-530 for 12 weeks

Subject must be HCV treatment-naïve or have failed previous HCV treatment.
Subject must be non-cirrhotic.

Estimated Enrollment: 321
Study Start Date: November 2015
Estimated Study Completion Date: February 2017
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)

---------------------------------------------------------------------------

A Randomized, Open-Label, Active-Controlled, Multicenter Study to Compare Efficacy and Safety of ABT-493/ABT-530 to Sofosbuvir Co-Administered With Declatasvir in Adults With Chronic Hepatitis C Virus Genotype 3 Infection

ABT-493/ABT-530 QD for 12 weeks
SOF 400 mg QD + DCV 60 mg QD for 12 weeks

Subject must be treatment-naïve
Subjects must be non-cirrhotic

Estimated Enrollment: 345
Study Start Date: November 2015
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)

[NY1972]

MRK will complete P2 when ABBV wraps up P3. It made a lot of protocol changes on 10/26:

GT2 C Grazoprevir+MK-3682+MK-8408 (6 weeks) => GT2 C Grazoprevir+MK-3682+MK-8408 (12 weeks)


A Phase II, Randomized, Open-Label Clinical Trial to Study the Efficacy and Safety of the Combination Regimen of MK-5172 and MK-3682 With Either MK-8742 or MK-8408 in Subjects With Chronic HCV GT1 and GT2 Infection

Estimated Enrollment: 465
Study Start Date: January 2015
Estimated Study Completion Date: November 2016
Estimated Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)

[NY1972]

ENDURANCE-4 started recruiting

The Efficacy and Safety of ABT-493/ABT-530 in Adults With Chronic Hepatitis C Virus Genotype 4, 5, or 6 Infection (ENDURANCE-4)

Estimated Enrollment: 130
Study Start Date: November 2015
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)

[DewDiligence]

AL-704 is AL-335's backup?

It was.

[NY1972]

According to the trials' start dates, AL-704 is AL-335's backup??



First in Human Study of AL-335; Single Dose, Food Effect in Healthy Volunteers; Multiple Doses in Chronic Hepatitis C Genotype 1

Estimated Enrollment: 70
Study Start Date: December 2014
Estimated Study Completion Date: June 2015


First in Human Study of AL-704; Single Dose, Food Effect in Healthy Volunteers; Multiple Doses in Chronic Hepatitis C
Estimated Enrollment: 96
Study Start Date: July 2015
Estimated Primary Completion Date: November 2015

[DewDiligence]

Re: JNJ’s HCV program

Please see #msg-119319641. (My prior post on this subject was mistaken and has been deleted.)

[NY1972]

The implication from Medivir’s PR is that JNJ’s HCV program, if not dead, is on life support. JNJ still has the HCV compounds acquired from ACHN, but without the Alios nuke [AL-704] it’s hard to see a viable business plan here.

Are AL-335 and AL-516 backups?

[DewDiligence]

Will FDA follow suit?

No. Once the FDA accepts an application with a priority review, they don’t revoke the preview review. The PDUDA date for MRK’s 2-DAA regimen is 1/28/16.

[NY1972]

Large block after MRK news.

16:23 $ 31.73 300,100

[NY1972]

MRK—EMA nixes “accelerated assessment” of 2-DAA* HCV regimen and will review the application on a standard timetable

Will FDA follow suit?

[DewDiligence]

MRK’s HCV regimen delayed slightly in EU: #msg-119266731.

[DewDiligence]

ENTA names Chairman of BoD:

http://finance.yahoo.com/news/enanta-pharmaceuticals-announces-election-bruce-130000008.html

Enanta Pharmaceuticals, Inc…today announced the Board of Directors has elected Bruce L.A. Carter, Ph.D. as non-executive Chairman of the Board. Dr. Carter has been an independent director of Enanta since November 2013. He currently serves as the Chair of the Compensation Committee and is a member of the Nominating and Corporate Governance Committee.

…Dr. Carter received a B.Sc. with Honors in Botany from the University of Nottingham, England, and a Ph.D. in Microbiology from Queen Elizabeth College, University of London.

[DewDiligence]

The 10-K for the fiscal year ending 9/30/15 has been filed:

http://www.sec.gov/Archives/edgar/data/1177648/000119312515401602/d21127d10k.htm

[DewDiligence]

Short Interest = 4,236,497.

The increase from the previous reading (on 11/13/15) is only 147K shares, so I wouldn’t ascribe too much meaning to the change.

[NY1972]

Short Interest = 4,236,497

Shorts are really confident ABBV will have the LEAST sustainable HCV franchise.

[DewDiligence]

FDA accepts NDA for qD formulation of V-Pak: #msg-118870098.

[NY1972]

ABBV keep prices reasonable.

http://www.bloomberg.com/news/articles/2015-12-01/gilead-used-revenue-driven-pricing-on-hep-c-drug-senators-say?cmpid=yhoo.headline

That tough negotiating applied to the U.S.’s taxpayer-funded health programs, as well as private insurers. The company offered supplemental rebates of 10 percent to Medicaid, the state-run, U.S.-funded health insurance program for the poor, the senators said. Those rebates, however, came with the condition that states had to drop some or all of their access restrictions, according to the Senate investigation. Only five state Medicaid programs reached agreements to receive extra rebates in 2014, the Senate investigation found.
Prices only dropped for Gilead’s hepatitis drugs after a competing treatment from AbbVie Inc. entered the market in December 2014. That led to the nation’s largest drug benefit manager, Express Scripts Holding Co., making AbbVie’s drug Viekira Pak the preferred treatment for the most common sub-type of the virus, according to the statement.

[semi_infinite]

CFO risk management - he seems to be content to keep his long exposure under 90K shares. So far this year, he sold about 70K shares offset by 30K options. He started the year with around 125K shares.

http://www.sec.gov/cgi-bin/browse-edgar?action=getcompany&CIK=0001185034


CEO started the year with around 520K shares and currently at 545K shares plus 110K options.
http://www.sec.gov/cgi-bin/browse-edgar?action=getcompany&CIK=0001571211

[DewDiligence]

ENTA needs safety data on EDP-494 before we talk about adding it to regimens willyw-nilly (heheh).

[NY1972]

Were it to be that the new ENTA cyclophillin inhibitor could be added to Abbies 2nd gen program, the Gilead triple might no longer be the best.

If EDP-494 is as good as Luly claimed, J&J and Merck would also want to try it with their HEP C regiment too. They need to try a hail Mary pass to stay in the game.

[DewDiligence]

For treating patients with RAVs from prior DAA failure, the duration of the regimen used for re-treatment is much less consequential than its success rate. I.e., the one thing you absolutely want to avoid is a second treatment failure, possibly leaving the uncured patient with RAVs to overcome.

Even for treatment-naive patients, almost everyone who follows this field of medicine thinks that 4-week regimens are too short. 6-week regimens might be possible for the easiest-to-treat patients, but cutting out only 2 weeks (relative to an 8-week regimen) may not be worth the increased risk of relapse.

[NY1972]

Can ENTA come up with a 4, 6 week regiment? Every Goliath has failed so far. According to GILD followers, whatever ENTA creates will be "Too little, too late".


"In this program, we've seen uniform activity of EDP-494 against all HCV genotypes tested so far namely genotypes 1 through 5 and perhaps more importantly uniform activity against all genotype1 RAVs tested today including RAVs from all the major DAA classes. These classes include NS3 protease, NS5A, NS5B polymerase inhibitors both nuc and non-nuc."

[DewDiligence]

Transcript* of ENTA’s FY4Q15 CC:

http://finance.yahoo.com/news/edited-transcript-enta-earnings-conference-065602553.html

*Includes some errors.

[DewDiligence]

NVS obtained its cyclophilin inhibitor from Debiopharm, who reclaimed the rights to the compound when NVS pulled out.

[rajaram46]

Why the downward reaction this morning in ENTA?

Didn't think anything of note was in the conference call yesterday.

[willyw]

ENTA CC a few thoughts.
It's a pretty rough translation at times, but read and enjoy; (this was from the page 5 Q and A)

http://seekingalpha.com/article/3708036-enanta-pharmaceuticals-enta-ceo-jay-luly-on-q4-2015-results-earnings-call-transcript?page=5&p=qanda&l=last

Q and A
colin from Robert W. Baird & Co.
Luly's answer was that the G-1 8 week had essentially 100% cure rate, except for the cancer patient that died and didn't complete.
You will also notice that the 8 week SVR rates were very close to the 12 week trials.
I interpret that when greater numbers roll in that the 8 week trials for Geno 1's will look quite good

One of the disadvantages of Viekira has been twice a day, and that should switch to once a day dosing. (in 2016 if FDA approved?)
Europe and Japan are solid G1b populations where riba is not needed for Viekira.
In G1b cirrhotics, I think they are seeing that even riba added doesn't add much to the cure rates.
Point is.... Merck may not be such a shoo in for 2nd place, particularity on how the program gets labeled w/ regard to RAVs.


FWIW, Gild took 7977 through phase 3 trials in just 2 years to approval, but with several 24 week trial cohorts.
I would guess that since the trial cohorts will be 12 weeks, but who knows; there may be some conservative ones for treating cirrhotics, or contrasting 12 to 24 weeks (or 18?)
I expect approval in late 2017

I'm expecting better cure rates for the 3rd phase 2nd gen program than we are currently seeing, due to the higher (300 mg ABT-493) dose formula, and based upon the smaller data reported and a few flukes that skewed the SVR rates. I continue to believe that there were some later 2nd gen data that is wrapping up but has not/ was not reported at AASLD.


Nothing to do with the CC, but the Viekira prescriptions have been slowly raising, and the Harvoni, slowly decreasing.

I'm still kinda wondering, what this drug combo would do if combined with Sovaldi? Would it be better than the GILD triple DAA? (efficacy, duration, or curing certain genotypes/subgroups?)

[NY1972]

Is NVS the only pharma that put a cyclophilin inhibitor thru clinical trials? Merck, J&J and Gilead seem to be fixated on NS5B inhibitor?

[DewDiligence]

FY4Q15 CC notes: #msg-118709130.

[DewDiligence]

That SeekingAlpha write-up is moronic (eom).

[NY1972]

It is obvious I am no PhD, not a researcher either. Trying to learn something from Dew and WillyW everyday.

Thanks for reminding me.

[NY1972]

Latest free warning from SA for the funds that own 80% ENTA shares:

"If you are holding ENTA or thinking about buying, you should be warned that it is a very risky play and should protect yourself properly"

http://seekingalpha.com/article/3702916-a-fundamental-perspective-on-enanta-pharmaceuticals

Did anyone buy EXEL for a buck and change when another SA writer predicted it's demise?

[NY1972]

I think Luly should be ready to buy shares when FDA changes V Pak's label again, instead of watching the shorts decimate the SP to all time low.

[semi_infinite]

He bought almost 70K shares through early exercise of options on 10/23.

http://www.sec.gov/Archives/edgar/data/1177648/000090866215000319/xslF345X03/edgar.xml

[NY1972]

If he is confident in 2nd gen combo, Luly should buy back 10K shares @ $30 everyday with that $30 million. How about buying 8 million CNAT shares to finance their P2 trials?

[DewDiligence]

ENTA receives $30M milestone from ABBV for HCV launch in Japan:

http://www.sec.gov/Archives/edgar/data/1177648/000119312515382975/d214977d8k.htm

[DewDiligence]

Thanks. Nothing new there—the analysts cited by Barron's have been talking up GILD's HCV prospects in every write-up.

[semi_infinite]

Analyst comments with regard to next gen HCV competition.

http://blogs.barrons.com/stockstowatchtoday/2015/11/18/gilead-sciences-abbvie-merck-fail-to-mount-a-major-threat/?mod=yahoobarrons&ru=yahoo

[DewDiligence]

IMS forecasts $45-55B worldwide HCV-drug sales in 2020: #msg-118601117.

[willyw]

ENTA/ABBV/GILD - QUARTZ-I: Retreatment of HCV Genotype 1 DAA-failures With
Ombitasvir/Paritaprevir/r, Dasabuvir, and Sofosbuvir

http://www.natap.org/2015/AASLD/AASLD_20.htm

93% SVR12 rate in past DAA exposures
Very small study; 22 patients

[willyw]

100% SVR4 in HCV Genotype 1 Non-Cirrhotic Treatment-Naïve or -Experienced Patients With the Combination of ABT-493 and ABT-530 for 8 Weeks

http://www.natap.org/2015/AASLD/AASLD_21.htm

Per the link;
Geno 1 is a 46% prevalence world wide

This was in the higher optimized dosing;
300mg ABT-493 & 120 MG ABT-530

This is just a small trial, but others will be rolling in to confirm results.
Also please note, there is not a lot of difference between 12 and 8 weeks of treatment; close to statistically insignificant.

IMHO, the differences will show themselves in various treatment subtypes

[willyw]

Enta/Abbvie 2nd gen presentation; there should be more coming as AASLD wraps up

http://www.natap.org/2015/AASLD/AASLD_06.htm

A few comments

This treatment shines in genotype 1; currently the most important/highest prevalence genotype.

It appears that it will be competitive with Gilead's current Harvoni, and the next gen 2DAA (Sovaldi and GS5816)

It also appears that it will offer an 8 week treatment for at least some sub-groups (non-cirrhotic tx naives)

G-2 looks very good.
G-3 looks to be in the 95% range with just 2 pills
(Sof/Vel looks like 95% SVR rate, w/ 30% cirrhotic)

The 2nd gen data isn't as deep as the Gilead but it looks as though it may/should keep Abbvie in 2nd place in HCV.
FWIW, I believe there will soon be more 2nd gen data rolling in, but perhaps, post AASLD; in G-1 both 12 and 8 week, and in G-3 with the optimized dosing- (I presume just 12 weeks)

http://www.gilead.com/news/press-releases/2015/9/gilead-announces-svr12-rates-from-four-phase-3-studies-evaluating-a-oncedaily-fixeddose-combination-of-sofosbuvir-sof-and-velpatasvir-vel-gs5816-for-the-treatment-of-all-six-hepatitis-c-genotypes

I'm not seeing compelling data from JNJ, BMY or MRK.
(no surprise upsets)

Following AASLD data crunchers will have access to the data of HCV infected subgroups and patterns in response (cirrhosis, g-1a vrs 1B, past treatment failures, IL-28 subtypes (C/C, C/T, T/T), etc. (IFN based and past PI exposure)

Until this has been posted it's pretty difficult to compare all the new therapies, but it should soon become more clear.

[DewDiligence]

Why this Merck doublet is expected to beat up on V-Pak?

The only way that could happen is if MRK were to start a price war. Fortunately, ABBV’s V-Pak contracts with ESRX and several other US payers are already established for 2016.

[NY1972]

Why this Merck doublet is expected to beat up on V Pak? Based on data released, it can't handle RAVs and doesn't work well @ high VL "one at 948k, 3 between 1-2M iu/ml, 3 between 2-4M, 3 between 4-6M, 3 w VL 6M " .

[DewDiligence]

MRK's 3-DAA regimen doesn't look that great either:

#msg-118526734
#msg-118527569

[NY1972]

RAVs turn Merck doublet into loser?

Jacobson et al, clearly
demonstrate that in patients with baseline resistant variants (RAVs) who are
GT1a there is a significant difference in SVR12. Based on population
sequencing (high copy number of RAVs for detection), patients with protease
RAVs have an SVR12 of 58% vs 98% for those without (72% vs 98% with
lower cutoff of next-gen sequencing) and for the NS5a a similar pattern holds
where SVR12 is 72% for those with baseline RAVs and 98% for those without
(91% vs 98% with next-gen sequencing). Thus, it is clear the Merck doublet is
impacted by baseline resistance which could hamper its uptake.