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http://www.aasld.org/sites/default/files/2016-AbstractSupplement-TheLiverMeeting.pdf
(page 420)
849
Analysis of HCV Variants in the MAGELLAN-1 Part 1
Study: ABT-493 and ABT-530 Combination Therapy
of Genotype 1-Infected Patients Who Had Failed Prior
Direct Acting Antiviral-Containing Regimens
North Chicago, IL
Background: ABT-493 (NS3/4A protease inhibitor [PI] iden-
tified by AbbVie and Enanta) and ABT-530 (NS5A inhibitor) are next generation HCV direct-acting antiviral agents (DAAs).
Co-administration of ABT-493 + ABT-530 achieved a high
sustained virologic response 12 (SVR12) rate in DAA-naïve
patients with HCV genotype (GT) 1-6 infection, as well as GT1-infected patients who had previously failed a DAA-containing regimen.
.
In this report we present the characterization
of variants detected in samples from subjects enrolled in Part 1
of the MAGELLAN-1 study: treatment with ABT-493 + ABT-530
± RBV for 12 weeks in non-cirrhotic GT1-infected patients who
had previously failed regimens containing a PI and/or NS5A
inhibitor, ± an NS5B polymerase inhibitor.
Methods: Next generation sequencing (NGS) was performed on HCV NS3/4A and NS5A genes from all baseline samples and the first available sample after virologic failure with HCV RNA ≥
1000 IU/mL.
Sequencing results at 1% and 15% detection cutoffs were
examined for the presence of resistance-associated variants (RAVs) in the NS3 and NS5A genes.
Results: NGS (with 1% cutoff) of baseline samples from all patients (n=50) identified RAVs in 41 (82%) patients:
15 (30%) in NS3 only,
10 (20%) in NS5A only, and
16 (32%) in both targets
.
In 90% (37/41) of these samples, the RAVs were also present using an NGS detection cutoff of 15%. These DAA-experienced patient cohorts had broad representation of baseline variants at key resistance-associated positions, including those at NS3 V36, Q80, R155, and D168, as well as NS5A M28, Q30, L31, and Y93
.
All patients with baseline variants at position Y93 in
NS5A that confer high level of resistance to currently approved
NS5A inhibitors achieved SVR12 (n=10)
.
Of the 2 out of 50
(4%) patients who experienced virologic failure, 1 patient had
baseline NS3 (Y56H and D168A/T) and NS5A (M28V and
Q30L/R) RAVs, and the other patient had baseline RAVs in NS5A (L31M and H58D) only.
Conclusions: The combination of ABT-493 and ABT-530 demonstrated potent antiviral activity
and a high barrier to resistance in non-cirrhotic HCV GT1-in-
fected patients who had previously failed a DAA-containing regimen, regardless of the diverse profile and high prevalence of baseline NS3 and/or NS5A RAVs among these patients. These promising results support the study of this combination regimen in a larger cohort of DAA-experienced patients.
The renal impairment trial results- late breaker
http://www.aasld.org/sites/default/files/LBA%20Full%20Abstracts%20Final%20%28Trimmed%29_1.pdf
(page 8)
HEPATOLOGY, VOLUME 64, NUMBER 6 (SUPPL)
AASLD ABSTRACTS
1125A
LB-11
EXPEDITION-IV: Safety and Efficacy of GLE/PIB in Adults
with renal impairment and Chronic Hepatitis C Virus
Genotype 1 – 6 Infection
" Here we report on the safety and
efficacy of GLE/PIB administered for 12 weeks in GT1-GT6
HCV-infected patients with severe renal impairment (GLE was
identified by AbbVie and Enanta).
"RESULTS:
A total of 104 partici-
pants (76% male and 62% white) were enrolled in this study,
of whom 42% were TE and 19% had compensated cirrho-
sis. Patients had either GT1 (52%), GT2 (16%), GT3 (11%),
GT4 (19%), GT5 (1%) or GT6 (1%) chronic HCV infection and
had either CKD stage 4 (13%) or stage 5 (87%); 82% were
on dialysis. SVR4 was achieved by 103/104 (99%) patients.
The patient not achieving SVR4 prematurely discontinued treat-
ment. Most treatment emergent adverse events (AEs) were mild
or moderate in severity. Of the 24% of patients who experi-
enced serious AEs, none were related to study-drug. Four AEs
(4%) led to study-drug discontinuation and one patient died
after achieving SVR4 due to a serious AE not-related to study
drug (intracerebral hemorrhage).
CONCLUSIONS
The fixed
dose combination of GLE/PIB administered once daily for 12
weeks was well tolerated in patients with severe renal impair-
ment with 99% of patients achieving SVR4. Serious AEs were
considered unrelated to study drugs and associated with the
patients’ underlying comorbidities. T"
Comparing Abbvie's 2nd gen(G/P) to Gilead's triple.
http://www.aasld.org/sites/default/files/LBA%20Full%20Abstracts%20Final%20%28Trimmed%29_1.pdf
1126A
AASLD ABSTRACTS
HEPATOLOGY, December, 2016
LB-12
A Randomized Phase 3 Trial of Sofosbuvir/Velpatasvir/
Voxilaprevir for 8 Weeks Compared to Sofosbuvir/
Velpatasvir for 12 Weeks in DAA-Naïve Genotype 1-6
HCV-Infected Patients: The POLARIS-2 Study
=======================
(I have cut out some parts-view page to see full details~W)
This Phase 3 study (NCT02607800)
compared treatment with SOF/VEL/VOX fixed dose combi-
nation (FDC) for 8 weeks to SOF/VEL FDC for 12 weeks in
patients with genotype 1-6 HCV infection with and without
compensated cirrhosis who have not previously received treat-
ment with an HCV direct-acting antiviral agent (DAA).
Now compare to the Abbvie 8 week results;
http://investorshub.advfn.com/boards/read_msg.aspx?message_id=126481635
What appears to be a comparable test group
Genotype 1... ABBV G/P 8 wk 99% (348/351)
.......................GILD S/V/V 8 wk 96% (482/501)
Genotype 3...
...........ABBV G/P 8 wk 95% tx naivenon & noncirrhotic
...........GILD S/V/V 8 wk 100% (92/92) w/ % cirr
Genotype 2, 4, 5, & 6.. ABBV G/P 8 wk 97% (196/203)
........GILD S/V/V 8 wk G-2 97 (61/63)
.............................G-4 94 (59/63
.............................G-5 94 (17/18)
.............................G-6 100 (30/30)
GILD group G-2, 4, 5 & 6 is 174 patients compared to ABBV 203
The data shows very comparable 8 week results.
There is one difference however;
per the gilead late breaker
the group was DAA naive
On the other hand it appears that some exposure to sovaldi was allowed into Abbvie trials.
(from the endurance trial; HCV treatment-naïve or treatment experienced (IFN or pegIFN with or without RBV; SOF plus RBV with or without pegIFN).")
So there were some % of cirrhotics in Gilead trials; non in the abbvie
Obviously, not a 100% apples to apples comparison
Even so..... we will be able to detect some of the weaknesses when we compare therapies in shorter threshold treatment durations.
Both therapies look quite strong at 8 weeks and both will look very good at 12 weeks
This indicates to me that the Abbvie program looks very good compared even to Gileads triple; the top gun reserved for salvage.
I know it isn't a perfect comparison, but it is possible to look at comparable groups in 8 weeks. Thoughts? Any mistakes?
I'm busy and haven't looked at all the other trials or compared, but this looked noteworthy.
Worth mention.... some of the presentations at AASLD will provide final SVR data, so until that is known that final comparison isn't possible
~W
MRK’s 3-DAA HCV regimen fails to impress: #msg-126517784.
ENTA presents preclinical data for NASH compound, EDP-305 at AASLD:
#msg-126481843
ABBV/ENTA report 8w Glecaprevir/Pibrentasvir phase-3 data from three trials:
#msg-126481635
3Q16 Viekira sales $378M, -10% QoQ: #msg-126121950.
Musings on GILD’s POLARIS studies of 3-DAA HCV regimen:
#msg-125928919
Second generation direct-acting antivirals – Do we expect major improvements?
http://www.journal-of-hepatology.eu/article/S0168-8278%2816%2930331-2/fulltext
Detailed and objective.
We will see what data gets added to this at AASLD
It won't be long before the late breakers get listed.
Some of the blanks may not be filled in until the actual presentations and final data are presented.
ENTA-related excerpts from C&EN NASH article: #msg-125551256.
Per the AASLD abstracts, I am seeing high cure rates w/ the ABT 493/530 doublet. I am also seeing that latter stage trials are including the compounds, co-formulated.
The genotype 3 data looks really good; lets just say that it would be difficult to improve a G-3 treatment naive without cirrhosis cure rate.
The G-3 naive w/ compensated cirrhosis was good but being studied in 16 weeks of TX, in order to get it closer to the non-cirrhotic results.
I'm uncertain as to how much is permissible to post
By the way... the MRK triplet data looks really good, except for AE events.
I think I see Gilead market share erosion. Market agrees this morning.
ABBV/ENTA's second-generation HCV regimen gets FDA BTD for GT1 DAA-treatment failures:
#msg-125491435
ENTA presents ex-vivo data on lead RSV candidate:
http://finance.yahoo.com/news/enanta-pharmaceuticals-presents-data-novel-200600789.html
ENTA starts phase-1 trial of EDP-305: #msg-125454754.
First 8-week V-Pak data shows 98% SVR12 in treatment-naïve GT1b patients:
#msg-125342507
Slide set from Morgan Stanley webcast on 9/12/16:
http://phx.corporate-ir.net/External.File?t=1&item=VHlwZT0yfFBhcmVudElEPTUyMzYyODd8Q2hpbGRJRD02NDU0MzI=
Baird Q&A presentation
http://wsw.com/webcast/baird46/enta/index.aspx
Yup; I've seen it in two forums. 3 pills is what I have read.
I don't know the rules about reformulating it into 1 pill, but the dosage suggested it could all be combined into 1 pill
I don't follow it either; I'm just reporting
" My only side effect was insomnia and I don't know the drugs caused it. I took 3 pills a day for 12 weeks. I've been virus free for 5 weeks. They don"
I was looking for a second post from another forum. I think it was 3 also
I don't understand why ABT-493/ABT-530 would consist of three FDC pills. We talked about the rationale for using two identical FDCs in #msg-123225583.
Ah Good! I'm half surprised. They have really guarded the terms of it.
The cyclophilin inhibitor *could* produce what may be record log drops. It seems to do so comparatively invitro. What would the market think if it saw a 5-6 log drop in monotherapy in the trials?
…does [ENTA’s royalty] formula combine sales of 1st- and 2nd-gen programs to hit tiers?
Rocky wrote;
with the overall HCV market going down, ENTA needs to get double or triple the current market share to be meaningfully profitable. Not impossible, but seems unlikely.
The higher royalty payments will be meaningful if market share goes up.
Milestone payments will make it even more like a bank. The higher royalty payments will be meaningful if market share goes up. Since expenses are increasing, royalties and sales will have to go up for any real income to fall to bottom line. We "know" US sales of V-Pak will be down significantly in 3rd (and probably 4th) quarters. Probably not a huge deal since they already so low. Only hope until next generation is increased Japanese sales, but didn't do much for this quarter (increase of $1MM of royalties). More than ever, this is a next generation story and, with the overall HCV market going down, ENTA needs to get double or triple the current market share to be meaningfully profitable. Not impossible, but seems unlikely. Hope that I am wrong.
$80M of milestone payments are coming for next-gen HCV regimen (in addition to higher royalties).
"Revenue for the three months ended June 30, 2016 was $14.0 million, compared to $11.6 million for the three months ended June 30, 2015."
Shouldn't Enanta Pharma's charter be changed to a bank? Not much revenue, unfortunately..
ENTA had $244.7M of cash at 6/30/16, a decrease of $900K relative to 3/31/16:
http://ir.enanta.com/phoenix.zhtml?c=147990&p=irol-newsArticle&ID=2193820
Viekira sales by calendar quarter: #msg-124189583.
1. Why hasn't ABBV been able to sell more of their HCV drug, relative to GILD's sales?
2. Do you believe the newly approved once-per-day pill will make any difference in sales?
3. Do you believe ABBV will be able to compete better with their next-gen drug?
Dew -
1. Why hasn't ABBV been able to sell more of their HCV drug, relative to GILD's sales?
2. Do you believe the newly approved once-per-day pill will make any difference in sales?
3. Do you believe ABBV will be able to compete better with their next-gen drug?
Thanks Dew.
FDA apparently approved the once-daily formulation of Viekira Pak, called “Viekira XR”:
#msg-124098379
CHMP Grants Positive Opinion for Shorter Treatment Duration with AbbVie's VIEKIRAX® (ombitasvir/paritaprevir/ritonavir table...
Print
ENANTA PHARMACEUTICALS INC (NASDAQ:ENTA)
Intraday Stock Chart
Today : Monday 25 July 2016
Click Here for more ENANTA PHARMACEUTICALS INC Charts.
NORTH CHICAGO, Ill., July 25, 2016 /PRNewswire/ -- AbbVie (NYSE: ABBV), a global biopharmaceutical company, announced today that the European Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has granted a positive opinion for the use of 12 weeks of VIEKIRAX® (ombitasvir/paritaprevir/ritonavir tablets) with ribavirin (RBV) in genotype 4 (GT4) chronic hepatitis C virus (HCV) infected adult patients with compensated cirrhosis (Child-Pugh A). VIEKIRAX with RBV is currently approved in the European Union for GT4 patients with compensated cirrhosis for 24 weeks.
"Through optimizing the use of VIEKIRAX, AbbVie strives to meet the needs of patients and physicians, including a shortened treatment duration," said Michael Severino, M.D., executive vice president, research and development and chief scientific officer, AbbVie. "This milestone is progress toward an approval that would allow us to provide the opportunity for a cure with just 12 weeks of our regimen to genotype 4 patients with or without compensated cirrhosis in Europe."
Chronic HCV affects more than 160 million people worldwide,4 with 34 million people living with GT4 HCV infection.3 In Europe, where nine million people are infected with HCV,2 GT4 is becoming increasingly prevalent in several countries including Italy, France, Greece and Spain, where prevalence rates from 10 to 24 percent have been reported.3
The CHMP positive opinion is supported by data from a dedicated Phase 3 AGATE-I study of GT4 HCV infected patients with compensated cirrhosis. The randomized, open-label study evaluated the safety and efficacy of VIEKIRAX and RBV for 12 and 16 weeks. Results from the study showed that with 12 weeks of treatment with VIEKIRAX and RBV, 97 percent (n=57/59) of patients achieved sustained virologic response at 12 weeks post-treatment (SVR12 ).1
"Until recently people living with genotype 4 chronic hepatitis C had limited treatment options," said Tarik Asselah, M.D., lead study author and professor at Université Paris Diderot. "If approved, this 12-week treatment would mark another step forward in the cure for GT4 patients, allowing difficult-to-cure patients with compensated cirrhosis to be treated in half the time with VIEKIRAX, representing a significant benefit for both them and their physicians."
Results from the AGATE-I study also showed that patients treated with 16 weeks of VIEKIRAX and RBV achieved 98 percent (n=60/61) SVR12 rates. The most commonly reported adverse events (≥20 percent) in the 12-week arm were asthenia, fatigue and headache (18 percent, 17 percent and 23 percent respectively); and for the 16 week arm were fatigue, asthenia, headache, anemia, nausea, and pruritus (33 percent, 32 percent, 23 percent, 23 percent and 20 percent respectively).1 One patient in the 12-week group experienced virologic breakthrough and one discontinued prematurely after the first day of treatment. One patient missed the post-treatment week 12 visit in the 16-week group.1 The full study results were published online in The Lancet in June 2016.
About VIEKIRAX®
VIEKIRAX is approved in the European Union for the treatment of genotype 4 (GT4) chronic HCV infection. VIEKIRAX tablets consist of the fixed-dose combination of paritaprevir 150mg (NS3/4A protease inhibitor) and ritonavir 100mg with ombitasvir 25mg (NS5A inhibitor), dosed once daily.
Currently, in GT4 HCV infected patients VIEKIRAX with RBV is taken for 12 weeks, except in patients with compensated cirrhosis (Child-Pugh A), who should take it for 24 weeks.
Paritaprevir was discovered during the ongoing collaboration between AbbVie and Enanta Pharmaceuticals (NASDAQ: ENTA) for hepatitis C protease inhibitors and regimens that include protease inhibitors. Paritaprevir has been developed by AbbVie for use in combination with AbbVie's other investigational medicines for the treatment of chronic hepatitis C.
Additional information about AbbVie's hepatitis C development program can be found on www.clinicaltrials.gov.
EU Indication
VIEKIRAX is indicated in combination with other medicinal products for the treatment of chronic hepatitis C (CHC) in adults.
Important EU Safety Information
Contraindications:
VIEKIRAX is contraindicated in patients with severe hepatic impairment (Child-Pugh C). Patients taking ethinyl estradiol-containing medicinal products must discontinue them and switch to an alternative method of contraception prior to initiating VIEKIRAX. Do not give VIEKIRAX with certain drugs that are sensitive CYP3A4 substrates or strong inhibitors of CYP3A4. Do not give VIEKIRAX with strong or moderate enzyme inducers.
Special warnings and precautions for use:
VIEKIRAX is not recommended as monotherapy and should be used in combination with other medicinal products for the treatment of hepatitis C infection.
Risk of Hepatic Decompensation and Hepatic Failure in Patients with Cirrhosis
VIEKIRAX is not recommended in patients with moderate hepatic impairment (Child-Pugh B). Patients with cirrhosis should be monitored for signs and symptoms of hepatic decompensation, including hepatic laboratory testing at baseline and during treatment.
ALT elevations:
Transient elevations of ALT to >x5 ULN without concomitant elevations of bilirubin occurred in clinical trials with VIEKIRAX and dasabuvir with or without ribavirin and more frequent in a subgroup who were using ethinyl estradiol-containing contraceptives.
Pregnancy and concomitant use with ribavirin:
Extreme caution must be taken to avoid pregnancy in female patients and female partners of male patients when VIEKIRAX is taken in combination with ribavirin, see section 4.6 and refer to the Summary of Product Characteristics for ribavirin for additional information.
Use with concomitant medicinal products:
Use caution when administering VIEKIRAX with fluticasone or other glucocorticoids that are metabolized by CYP3A4. A reduction in colchicine dosage or interruption in colchicine is recommended in patients with normal renal or hepatic function. VIEKIRAX with or without dasabuvir is expected to increase exposure of statins so certain statins need to be discontinued or dosages reduced. Low dose ritonavir, which is part of VIEKIRAX, may select for PI resistance in HIV co-infected patients without ongoing antiretroviral therapy. HIV co-infected patients without suppressive antiretroviral therapy should not be treated with VIEKIRAX.
Adverse Reactions:
Most common (>20%) adverse reactions for VIEKIRAX and dasabuvir with RBV were fatigue and nausea.
Full summary of product characteristics is available at www.ema.europa.eu.
Globally, prescribing information varies; refer to the individual country product label for complete information.
About AbbVie
AbbVie is a global, research-based biopharmaceutical company formed in 2013 following separation from Abbott Laboratories. The company's mission is to use its expertise, dedicated people and unique approach to innovation to develop and market advanced therapies that address some of the world's most complex and serious diseases. Together with its wholly-owned subsidiary, Pharmacyclics, AbbVie employs more than 28,000 people worldwide and markets medicines in more than 170 countries. For further information on the company and its people, portfolio and commitments, please visit www.abbvie.com. Follow @abbvie on Twitter or view careers on our Facebook or LinkedIn page.
Forward-Looking Statements
Some statements in this news release may be forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions, among others, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated in the forward-looking statements. Such risks and uncertainties include, but are not limited to, challenges to intellectual property, competition from other products, difficulties inherent in the research and development process, adverse litigation or government action, and changes to laws and regulations applicable to our industry. Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," in AbbVie's 2015 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission. AbbVie undertakes no obligation to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.
1 Asselah T, Hezode C, Qaqish R. et al. Ombitasvir, paritaprevir, and ritonavir plus ribavirin in adults with hepatitis C virus genotype 4 infection and cirrhosis (AGATE-I): a multicentre, phase 3, randomised open-label trial. The Lancet Online. Accessed 22 June 2016; http://www.thelancet.com/pdfs/journals/langas/PIIS2468-1253(16)30001-2.pdf.
2 Hatzakis, A. et al. The state of hepatitis B and C in Europe: report from the hepatitis B and C summit conference. Journal of Viral Hepatitis, 2011; 18 (Suppl. 1):1-16.
3 Khattab MA, et al. Management of hepatitis C virus genotype 4: Recommendations of an International Expert Panel. J Hepatol. 2011; 54: 1250–1262.
4 Lavanchy D. Evolving epidemiology of hepatitis C virus. Clin Microbiol Infect. 2011; 17(2):107-15.
FY3Q16 earnings on 8/8/16—CC at 4:40pm ET:
http://finance.yahoo.com/news/enanta-pharmaceuticals-host-conference-call-113000022.html
Note: ABBV’s 2Q16 earnings and CC are on 7/29/16.
Epclusa is mainly for GT3: #msg-123576073.
FDA approves first pill to treat all forms of hepatitis C
The Food and Drug Administration approved the combination pill, Epclusa, from Gilead Sciences for patients with and without liver damage.
Read more: http://www.cnbc.com/id/103751499
ENTA begins EDP-494 dosing in GT1/GT3 HCV patients: #msg-123405434.
Market has no love for ENTA right now.
Nitpick: Since ENTA uses an Oct–>Sep fiscal year, evaluating results on a calendar-year basis can be misleading. For instance, ENTA’s guidance for the tax rate is set according to expectations for the full fiscal year.
Jay Luly exercised and held 25K options today: #msg-122543374.
ENTA had $245.6M of cash at 3/31/16 (a reduction of $8.9M relative to 12/31/15):
http://finance.yahoo.com/news/enanta-pharmaceuticals-reports-financial-results-200200117.html
Looks like Yahoo says that calendar year earnings are estimated at ~.30/sh and '17 earnings negative. Sure seems to low to me. If 3/31/16 quarter can repeat 12/31/15 royalty (and I think that they should be higher due to Japanese sales more than replacing the decline in the US, which is down ~20% QOQ at this point), there should be >.20/sh income.
I still think that ENTA can earn ~$1/sh+ in calander '16,
Well, it's been a brutal few days. : )
One could get discouraged.
In mid june Gilead should get Sov/Vel approved,
and we may get a read out on the Abbvie 2nd gen program by summer....perhaps.
So there may be better days ahead for GILD, and the potential for the Abbvie 2nd gen may improve ENTA's current slump.
Merck has been ruining Gilead's and Abbvie's picnic near term.
What does their long term game look like?
http://www.natap.org/2016/EASL/EASL_38.htm
This is their triple therapy; 8 weeks.
How does it stand up to Gilead's double or triple therapy?
How does it stand up to Abbvie's 8 or 12 week 2nd generation doublet?
Keep in mind.....
These 8 week values are for treatment naives; not even exposure to IFN
Neither Gilead or Abbvie want to lower prices, because they have viable 2nd (or 3rd) gen programs. Maybe Merck doesn't care cause they aren't a long term player (I dunno; I wonder)
Dew, I expect you misquoted me as I doubt I said the death of ENTA as I'm long....
You announced the death of ENTA on this board last October. Don't make the same mistake again.
This stock is sure being ripped apart for a company that has a three year run way.
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