Idenix hep C polymerase inhibtor shows promise in mid-stage study...

Posted 6/19/2012 on the Chicago Tribune website. Not a whole lot of info in this bare-bones press release, but it looks like Idenix's HCV polymerase inhibitor IDX184 is faring pretty well, at least with an n=31 in this mid-stage clinical trial in combo with P/R. More info to follow as soon as I can dig some up. 

Idenix hep C drug shows promise in mid-stage study
 
Reuters
4:34 p.m. CDT, June 19, 2012

(Reuters) - Idenix Pharmaceuticals Inc said interim data from a mid-stage trial on its experimental hepatitis C drug showed promise, sending its shares up 12 percent.

The drug, IDX184, was given to 31 patients in combination with the standard hep C treatments pegylated interferon and ribavirin.

Nine patients received the combination therapy for 12 extended weeks and were checked four weeks later for signs of the virus in the blood to determine if there was a sustained virologic response, or SVR.

All four patients in the 100 mg arm and four out of five patients in the 50 mg arm achieved a sustained virologic response four weeks after the completion of treatment.

Patients who did not have undetectable levels of virus at 4 weeks and 12 weeks automatically entered the 36-week combination therapy extended treatment phase which is ongoing, the company said.

Idenix shares rose 12 percent to $10.45 in extended trade, after closing at $9.37 on Tuesday on the Nasdaq.

(Reporting by Shailesh Kuber in Bangalore; Editing by Saumyadeb Chakrabarty)

Abbott Laboratories releases data on PILOT & CO-PILOT studies...

The EASL madness begins! An article posted today on Wall Street Journal.com below on Abbott's (or soon-to-be spin-off AbbVie) PILOT and CO-PILOT studies looking at protease inhibitor ABT-450 and polymerase inhibitors ABT-072 and ABT-333.  These studies are remarkable for a couple of reasons in my view:

• Interferon-free regimens, at least for certain populations, is really a reality.
• An SVR12 of at least 90% (in the tx-naive, no complications populations) is the new 75% of last year.
• The majority of large pharma companies now in the HCV marketplace is astounding. Competition will be fierce.
• The prospects of a Novir-boosted HCV PI is questionable, especially with 4 severe adverse events attached to it. 
• The drug to really, really beat is Ribavirin. Don't say I didn't tell you so. 

This EASL is going to be a big one for HCV drug development - stay tuned!

Abbott Drugs Suppress Hepatitis C Virus In 2 Studies

--Abbott is testing several experimental hepatitis C drugs

--More than 90% of patients with no prior treatment in one study had suppressed virus 12 weeks after treatment

--Abbott is targeting launch of hepatitis C regimen in 2015

(Adds details of a Bristol-Myers study in final paragraph; updates stock prices.)


   By Peter Loftus
   Of DOW JONES NEWSWIRES

Experimental drugs from Abbott Laboratories (ABT) suppressed the hepatitis C virus in most patients in two small, midstage studies.

The results unveiled Wednesday could reinforce Abbott's position as a key player in an industry race to bring the next generation of drugs to what is expected to be a multibillion-dollar market for hepatitis C therapies. The drugs' safety and efficacy, however, need to be confirmed in additional studies.

"The Abbott data are clearly impressive from an efficacy perspective," said ISI Group analyst Mark Schoenebaum.

Abbott shares rose 36 cents, or 0.6%, to $61.50 in recent trading, and earlier set a 52-week high of $62.57.

Abbott has said it could begin selling a new hepatitis C regimen in 2015, and sales could eventually exceed $2 billion annually. The drugs would be sold by the pharmaceutical business that Abbott plans to split off into an independent company later this year, to be named AbbVie.

Summaries of the Abbott studies and studies of other liver-disease drugs were posted online Wednesday by the European Association for the Study of the Liver, or EASL, in advance of its annual scientific meeting in Barcelona in mid-April. Some EASL study results won't be released until the conference begins in two weeks, including data for key drugs from Gilead Sciences Inc. (GILD) and Bristol-Myers Squibb Co. (BMY).

Gilead, Bristol-Myers, Vertex Pharmaceuticals Inc. (VRTX) and Merck & Co. (MRK) are among several companies developing hepatitis C drugs to tap a market that research firm Decision Resources predicts will hit $16 billion in 2015, up from just $1.7 billion in 2010.

Hepatitis C is a viral disease that attacks the liver, and is believed to afflict about 180 million world-wide, with more than 4 million in the U.S., according to the National Institute of Allergy and Infectious Diseases. At-risk groups include people who had blood transfusions before 1992, when a screening test for the virus was developed.

Abbott is developing several potential hepatitis C drugs. One of them, ABT-450, is a so-called protease inhibitor, which is the same class of drugs as two that went on sale last year, Merck's Victrelis and Vertex's Incivek, which is marketed outside the U.S. by Johnson & Johnson (JNJ) as Incivo.

The protease inhibitors advanced treatment of hepatitis C, but there is still room for improvement because current treatments require an injectable drug, interferon, that can be difficult for patients to tolerate. Abbott and other companies want to develop all-oral regimens that eliminate the need for interferon.

In addition, Abbott is developing two polymerase inhibitors, ABT-072 and ABT-333, which have different mechanisms of action than the protease inhibitors.

The two studies released Wednesday each focused on ABT-450. One, titled "Co-Pilot," involved 50 patients who were given the following: one of two different dose levels of ABT-450, combined in the same pill with Abbott's Norvir boosting agent; ABT-333; and an existing drug called ribavirin that is part of the current standard of care for hepatitis C. The regimen amounted to several pills taken daily.

The study tested safety and tolerability of a 12-week regimen of the drugs in people with the most common form of hepatitis C, known as genotype 1. Patients in the study either hadn't previously received any treatment or didn't respond to prior treatment.

In the treatment-naive patient groups, more than 90% had a sustained virologic response 12 weeks after the end of treatment, a measure known as SVR12. Sustained virologic response is roughly equivalent to being virus-free or having nearly undetectable viral levels.

In the patients who didn't respond to prior treatment, 47% achieved SVR12 in the Abbott-funded study.

The second, smaller study--called "Pilot"--combined ABT-450 boosted by Norvir, ribavirin, and ABT-072. All 11 patients had received no prior therapy. This group of patients had a subtype of the virus that generally responds well to an interferon-based regimen and thus considered among the easier forms to treat.

Ten of the 11 patients achieved a sustained virologic response 24 weeks after stopping treatment, for an SVR24 rate of 91%. One patient relapsed.

"We're showing a sustained, post-treatment response from 12 to 24 weeks out" from the end of treatment, said Scott Brun, divisional vice president of infectious disease development at Abbott.

In both studies, the most common adverse events included headache, fatigue and nausea, and most were mild. In the larger "Co-Pilot" study, four patients had severe adverse events including fatigue and vomiting. There were no deaths in either study.

Abbott is conducting larger mid-stage studies testing various combinations of the three experimental drugs used in the smaller studies, Brun said. Abbott hopes to move some combination of the drugs into late-stage testing next year.

Abbott has developed ABT-450 in collaboration with Enanta Pharmaceuticals.

Shares of some of Abbott's rivals in the hepatitis C field declined Wednesday. Idenix Pharmaceuticals Inc. (IDIX) dropped 14% to $8.77; Gilead was off 1.85% at $47.21; Vertex was down 2.5% at $40.73, and Bristol-Myers was down 0.6% at $33.66.

A summary of a Bristol-Myers study posted Wednesday by EASL showed that a regimen of the drugs daclatasvir and asunaprevir helped 90.5% of hepatitis C patients who hadn't responded well to prior therapy achieve sustained virologic response 12 weeks post-treatment. Some 64% of patients who were ineligible for interferon-containing regimens or who discontinued prior therapy for intolerance achieved SVR 12 with the Bristol regimen.

-By Peter Loftus, Dow Jones Newswires; 215-982-5581; peter.loftus@dowjones.com

BioCryst releases preclinical results for HCV nucleoside inhibitor BCX5191

Posted 2/15/12 on Business Wire -  BioCryst announce pre-clinical results for their once-a-day (concieveably) pan-genotypic polymerase inhibitor BCX5191, with first in-human study planned for Q4 2012. The authors of the press release invoke "GS-7977" in comparsion to BCX5191 in terms of internal comparative preclinical studies.

BioCryst Announces Promising Results from Preclinical Studies of BCX5191 for Hepatitis C


•BCX5191: Planning to file for first–in-human studies during the fourth quarter 2012
•BioCryst to discuss study outcomes during its 2011 results call February 16 at 11:00 a.m. ET

RESEARCH TRIANGLE PARK, N.C.--(BUSINESS WIRE)--BioCryst Pharmaceuticals, Inc. (NASDAQ: BCRX) today announced favorable preclinical results for BCX5191, a novel adenine nucleoside analog targeting viral RNA polymerase for the potential treatment of hepatitis C.

“Based on our internal comparative preclinical studies of BCX5191 with the most advanced nucleotide analog in clinical development, GS-7977, we believe BCX5191 has the potential to be the backbone of best-in-class oral treatment regimens for hepatitis C patients.”

.BioCryst has successfully completed in vitro and in vivo studies in which BCX5191 exhibited potent and selective pan-genotypic antiviral activity against the hepatitis C polymerase enzyme. BCX5191 showed no inhibition of human RNA polymerase and no evidence of toxicity from standard in vitro screens.

Human liver cells rapidly and efficiently convert BCX5191 into its active triphosphate form. BCX5191 does not require prodrug technology to achieve bioavailability. BCX5191 inhibits the viral RNA polymerase enzyme across genotypes 1-4 at sub-micromolar concentrations (0.05-0.36 µM) and is active in replicon cell assays for genotypes 1a and 1b.

In preclinical models, BCX5191 demonstrates high oral bioavailability, and the drug is actively transported into the liver. Following a single oral dose in rats, liver BCX5191 triphosphate levels exceed the IC50 values for genotypes 1-4 through 24 hours. At Cmax, the drug triphosphate level is more than 100 times the IC50. This pharmacokinetic profile is expected to support once-daily dosing in clinical studies.

“BCX5191 has met stringent preclinical criteria to advance to IND-enabling studies. We expect this program to be ready to file for first-in-human studies during the fourth quarter of 2012,” said Dr. William P. Sheridan, Senior Vice President & Chief Medical Officer of BioCryst Pharmaceuticals. “Based on our internal comparative preclinical studies of BCX5191 with the most advanced nucleotide analog in clinical development, GS-7977, we believe BCX5191 has the potential to be the backbone of best-in-class oral treatment regimens for hepatitis C patients.”

Additional BCX5191 non-clinical experiments are ongoing or planned, including Good Laboratory Practices (GLP) non-clinical safety studies and in vitro evaluation of BCX5191 in combination with ribavirin.

Conference Call and Webcast

BioCryst's leadership team will host a conference call and webcast on Thursday, February 16, 2012 at 11:00 a.m. Eastern Time to discuss financial results and recent corporate developments, including results from the BCX5191 hepatitis C program. To participate in the conference call, please dial 1-877-303-8027 (United States) or 1-760-536-5165 (International). No passcode is needed for the call. The webcast and accompanying slides can be accessed by logging onto www.BioCryst.com. Accompanying slides will be available on the BioCryst website several hours prior to the call. Please connect to the website at least 15 minutes prior to the start of the conference call to ensure adequate time for any software download that may be necessary.

About Hepatitis C

Hepatitis C is a contagious liver disease that results from infection with the hepatitis C virus (HCV), which is the most common virus that infects the liver and can lead to life-threatening liver problems, such as liver damage, cirrhosis, liver failure or liver cancer. There are an estimated 170 million individuals worldwide who are chronically infected with HCV, and about 3 to 4 million people are infected annually. In the United States, there are approximately 4 million people who have chronic hepatitis C.

About BioCryst

BioCryst Pharmaceuticals designs, optimizes and develops novel small-molecule pharmaceuticals that block key enzymes involved in infectious diseases, inflammatory diseases and cancer. BioCryst currently has three novel late-stage compounds in development: peramivir, a neuraminidase inhibitor for the treatment of influenza, BCX4208, a purine nucleoside phosphorylase (PNP) inhibitor for the treatment of gout, and forodesine, an orally-available PNP inhibitor for cancer, which is being developed by Mundipharma under a global license agreement. Utilizing crystallography and structure-guided drug design, BioCryst continues to discover additional compounds and to progress others through preclinical and early development to address the unmet medical needs of patients and physicians. For more information, please visit the Company's website at http://www.biocryst.com/.

Forward-Looking Statements

This press release contains forward-looking statements, including statements regarding future results, performance or achievements. These statements involve known and unknown risks, uncertainties and other factors which may cause our actual results, performance or achievements to be materially different from any future results, performances or achievements expressed or implied by the forward-looking statements. These statements reflect our current views with respect to future events and are based on assumptions and subject to risks and uncertainties. Given these uncertainties, you should not place undue reliance on these forward-looking statements. Some of the factors that could affect the forward-looking statements contained herein include: that there can be no assurance that our compounds will prove effective in clinical studies; that development and commercialization of our compounds may not be successful; that we or our licensees may not be able to enroll the required number of subjects in planned clinical trials of our product candidates and that such clinical trials may not be successfully completed; that BioCryst or its licensees may not commence as expected human clinical trials with BCX5191; that ongoing and future preclinical and clinical development may not have positive results; that we or our licensees may not be able to continue future development of our current and future development programs; that our development programs may never result in future product, license or royalty payments being received by BioCryst; that BioCryst may not reach favorable agreements with potential pharmaceutical and biotechnology partners for further development of BCX5191; that our actual cash burn rate may not be consistent with our expectations; that BioCryst may not have sufficient cash to continue funding the development, manufacturing, marketing or distribution of its products and that additional funding, if necessary, may not be available at all or on terms acceptable to BioCryst. Please refer to the documents BioCryst files periodically with the Securities and Exchange Commission, specifically BioCryst's most recent Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, and current reports on Form 8-K, all of which identify important factors that could cause the actual results to differ materially from those contained in our projections and forward-looking statements.


BCRXW

Contacts

BioCryst Pharmaceuticals

Robert Bennett, 919-859-7910 (investors)

or

WCG

Catherine Kyroulis, 212-301-7174 (media)

New MEDSCAPE article sheds more light on PSI-7977 and the ELECTRON trial...

Pharmasset launched a broadside in the HCV drug development wars during AASLD, revealing that some patients may be able to achieve and SVR without the use of interferon. This was according to nterim results from the phase II ELECTRON trial, looking at Pharmasset's nucleotide inhibitor PSI-7977 in various combinations with ribavirin and interferon/no interferon in different Hepatitis C genotypes. In one arm, PSI-7977 plus ribavirin was administered for 12 weeks in 10 genotype 2 and 3 patients. This article sheds further light on those patients - in short, they were genotype 2/3, tx-naïve without cirrhosis. They had a mean age of 47 years, mean baseline HCV RNA was 6.49 log10 IU/mL, and roughly 43% had the favorable 'CC genotype' associated with favorable response to standard interferon-based therapy. The author also interviews lead PI Edward Gane, MD and gets 'too good to be true?' thoughts from Michael Bernstein, MD who was involved in the NM-286 clinical trials.

From Medscape Medical News
New HCV Drug Achieves 100% Cure Rate Without Interferon

Neil Canavan

November 9, 2011 (San Francisco, California) — An interferon-free regimen for the treatment of infection with hepatitis C virus (HCV) might soon be available, according to data from the ELECTRON trial, presented here at The Liver Meeting 2011: American Association for the Study of Liver Diseases 62nd Annual Meeting.

In ELECTRON — 1 of 2 phase 2 studies of the investigational compound PSI-7977 (Pharmasset) reported here — an interferon-free regimen of PSI-7977 plus ribavirin achieved a 100% sustained viral response (SVR) at 12 weeks in all study subjects.

"PSI-7977 has the potential to dramatically change the treatment paradigm for HCV," said lead study investigator Edward Gane, MD, from Auckland City Hospital in New Zealand.

PSI-7977 is a uridine nucleotide analog polymerase inhibitor that is administered once daily with or without food. It has demonstrated robust activity in patients infected with HCV genotype 1 when used in combination with pegylated-interferon and ribavirin after a 12-week course.

Activity with this agent used as a monotherapy has also been reported.

"The aim of the ELECTRON trial was to determine the shortest duration of interferon, if any, required to achieve SVR when PSI-7977 plus ribavirin are administered for 12 weeks," Dr. Gane explained.

ELECTRON investigators recruited 40 patients who were randomized to 1 of 4 treatment groups: PSI-7977 400 mg plus ribavirin for 12 weeks plus interferon for 0, 4, 8, or 12 weeks.

Patients were treatment-naïve, noncirrhotic, infected with HCV genotype 2 or 3, and stratified by interleukin (IL)28B single-nucleotide polymorphisms (SNP) and HCV RNA levels. Mean age was 47 years and mean baseline HCV RNA was 6.49 log10 IU/mL, with 42.5% exhibiting the CC genotype at the IL28B SNP.

"We selected a genotype 2/3 population because this represents a population that would be more easily rescued with interferon in the event of virologic breakthrough," Dr. Gane explained.

Results after treatment initiation were dramatic. "All patients achieved a rapid virologic response, with over 80% being nondetectable at 2 weeks," reported Dr. Gane.

All patients had undetectable HCV at 3 weeks; furthermore, all patients achieved end-of-treatment response. No cases of treatment resistance were observed.

"Even following cessation of interferon, or with no interferon, there were no virologic breakthroughs on treatment." Also encouraging was the fact that all patients in the study experienced a rapid normalization of alanine aminotransferase.

There were no serious adverse events, and the mild to moderate events observed were attributed to either interferon or ribavirin. Significant improvements in safety and tolerability were seen in the interferon-free treatment group. No safety signals for PSI-7977 were observed, and there were no treatment-related discontinuations.

Results of the 12-week analysis prompted study investigators to add an exploratory treatment group of open-label PSI-7977 monotherapy for 12 weeks (n = 10). "The response was the same as with combination treatment with ribavirin," said Dr. Gane. Although this study is ongoing, 6 of 10 patients have achieved SVR at 4 weeks.

"These data clearly demonstrate that PSI-7977 exhibits high potency and has a high barrier to resistance," Dr. Gane said, noting that the drug is being advanced in phase 3 investigations in all HCV genotypes.

Too Good to be True?

Michael Bernstein, MD, director of the hepatitis clinic at the Coney Island Hospital, Brooklyn, New York, has doubts about PSI-7977. "If you use it with ribavirin and no interferon, you get a 100% SVR; if you use it alone, you get a 100% SVR."

Dr. Bernstein accepts the efficacy of PSI-7977 for the moment, but is concerned that ELECTRON isn't powered to say much about the tolerability or resistance profiles of the drug.

"What we've found with most of these [polymerase inhibitors] is that if you use them by themselves, you get resistance; if you don't, they can be very difficult to tolerate," said Dr. Bernstein. "There was a drug being investigated at Mount Sinai — a polymerase inhibitor, NM286 — and those patients got severe diarrhea and could not tolerate it. According to the ELECTRON study, everything was perfect — no gastrointestinal issues, no apparent adverse events of any kind, and it worked 100% of the time without interferon, or ribavirin.... If it's true, it will be great. The holy grail is to try to rid HCV treatment regimens of interferon."

Although sincerely impressed, Dr. Bernstein, who has seen many drugs come and go, suspects that as larger phase 3 trials of PSI-7977 are conducted, polymerase-associated adverse events, tolerability issues, and treatment resistance patterns will emerge.

Dr. Gane reports advisory board relationships with Pharmasset, Gilead, Roche, Janssen-Cilag, and Boehringer-Ingelheim. Dr. Bernstein has disclosed no relevant financial relationships.

The Liver Meeting 2011: American Association for the Study of Liver Diseases (AASLD) 62nd Annual Meeting: Abstract 34. Presented November 6, 2011.

Idenix starts recruiting for drug-drug interaction study evaluating the combination of IDX320 and IDX184 in healthy subjects

Idenix, Inc starts recruiting phase I, double-blind, multiple-dose study to evaluate the pharmacokinetic drug-drug interaction between it's protease inhibitior IDX320 and it's polymerase inhibitor IDX184 in healthy subjects
More info here: http://bit.ly/dlDQdC