Initial Abbott Labs interferon-free triple combination data released...

Posted 10/15/12 on Trust.org. The pre-AASLD press release parade is in full swing!! This time Abbott Labs checks in with some pretty impressive data (although you never know until you see the full abstract/presentation) with it's 3 drug interferon-free combo + ribavirin (HCV protease inhibitor ABT-450, polymerase inhibitor ABT-333 and NS5A inhibitor ABT-267 + RBV).  Although the numbers are small, 76 out of 77 treatment naive patients and 38 out of 41 null responders achieved SVR12. I believe, however, it was an Abbott's PILOT study looking at a combo of ABT-450 plus non-nuc ABT-072 and RBV where two patients experienced 'late relapse'... one at week 8 post-treatment and one at week 36. We'll have to see if 'late relapse' is a phenomena with just that certain combination or if a more robust 3 drug combination is enough to quash the virus for a true SVR.  I'd also like to see the IL28B genotype and sub-type of this study population, as well as BMI, steatosis and cirrhosis percentages as well. But without the benefit of an in-depth look under the hood,  this initial data looks pretty impressive. 

Mon, 15 Oct 2012 18:27 GMT
Source: Reuters // Reuters

* 99 pct of untreated patients achieve cure, or SVR, at 12 weeks

* 93 pct of previously unresponsive patients reach SVR at 12 weeks

* Abbott shares rise 3.3 percent (Adds analyst comment, updates shares)

By Bill Berkrot

Oct 15 (Reuters) - An all oral regimen of experimental hepatitis C medicines developed by Abbott Laboratories led to high cure rates in both new patients and those for whom prior treatment failed, according to initial results from a midstage study.

Shares of Abbott rose more than 3 percent after the unveiling of the data, which will be presented next month at a major liver disease meeting. The findings should help cement Abbott as a major player in the race to develop an interferon-free treatment regimen for the serious liver disease.

After 12 weeks of treatment with three Abbott direct-acting antiviral medicines plus the older drug ribavirin, 99 percent of previously untreated patients and 93 percent of those who did not respond to older drugs achieved a sustained virologic response (SVR), which is considered cured, according to available data from a brief summary, or abstract, of the study.

Abbott will present much more detail on the Phase II study involving data from more patients at the American Association for the Study of Liver Diseases (AASLD) meeting in Boston.

"The data looks very good on efficacy and I didn't see anything that really caught my eye as far as side effects," Morningstar analyst Damien Conover said.

Based on the results, Abbott said it would test its three drugs, each of which attacks the virus using a different approach, both with and without ribavirin in a large Phase III program aimed at gaining approval for the treatment.

"The ability to show a sustained virological response in these patient populations without the use of interferon is extremely encouraging," Scott Brun, Abbott's head of infectious disease development, said in a statement.

A pair of new hepatitis C drugs approved last year significantly boosted cure rates and cut treatment duration to as low as 24 weeks for some patients. But those must still be taken with interferon, an injected drug that often causes severe flu-like symptoms that lead many hepatitis patients to delay or discontinue treatment.

Several companies, including Gilead Sciences Inc, Bristol-Myers Squibb Co and Vertex Pharmaceuticals Inc , are racing to develop interferon-free treatment regimens expected to bring in billions of dollars in revenue once approved.

Most analysts view Gilead as current leader both on timing and perceived advantages of its experimental hepatitis C program.

"One of the questions lingering here is whether these (Abbott) drugs can be used without ribavirin," Conover said. "Gilead's drug works pretty well without it, so it's going to be a pretty big competitive hurdle if they have to use ribavirin."

While not as onerous as interferon, ribavirin also has side effects that doctors and patients would like to avoid if possible.

The Abbott drugs, a protease inhibitor called ABT-450, a polymerase inhibitor ABT-333 and ABT-267 from a class known as NS5A inhibitors, were given along with ribavirin for just 12 weeks. Patients in whom the virus was undetectable 12 weeks after stopping treatment were considered cured.

Based on available data at the time the abstract was submitted for the liver meeting, 76 of 77 previously untreated patients and 38 of 41 prior null responders had achieved SVR.

Null responders, while a much smaller market than new patients, have been notoriously difficult to treat.

"The data presented so far appear to be very favorable in these early trials and we'll look for more extensive data at AASLD," JP Morgan analyst Michael Weinstein said in a research note, adding that he expects Abbott's hepatitis C program to reach the market by 2015.

One subject in the new patient group had a disease relapse after treatment and three of the prior null responders experienced viral breakthrough, meaning the virus levels rose during treatment after an initial response.

The most common side effects were fatigue and headache in both groups. Of five reported serious adverse events, one - joint pain - was deemed to be possibly caused by study drugs, the company said.

Abbott shares were up $2.29, or 3.3 percent, at $71.57 at midday on the New York Stock Exchange after rising to a new high of $71.99 earlier. (Reporting by Bill Berkrot; Editing by Andrew Hay, Steve Orlofsky and M.D. Golan)

Seeking Alpha: Is The Hep C Drug Pipeline Beginning To Crack?

Posted on 8/19/12 on Seeking Alpha.com. Commentary by Tiran Rothman from Bioassociate Consulting on the current state of affairs in HCV drug development. His feeling is that the troubles with the NS5A inhibitors may give formerly dark horse companies developing drugs with differing approaches to tackle the virus (mentioned are BioLineRx with it's BL-8020 entry inhibitor and Transgene's TG4040 therapeutic vaccine) a chance to shine. 

Is The Hep C Drug Pipeline Beginning To Crack?

By Tiran Rothman

Another crack appeared today in the ultra-hype of next generation Hep C drugs. Idenix Pharmaceuticals (IDIX) released news that its Phase IIb trial with IDX184 was put on partial clinical hold by the FDA due to the recent cardiovascular toxicity experienced by a patient treated with a similar treatment developed by Bristol-Myers Squibb (BMY). Idenix's investors were quick to pull the trigger, sending the stock for a 40% nosedive.

Both Idenix's IDX184 and BMS's 094 are NS5 family inhibitors, which are the front line of Hep C drug candidates, destined to be part of an oral therapy regimen that will make the current use of interferon injections redundant. Even though there has been no evidence of cardiotoxicity in patients treated with IDX184, the FDA has expressed a concern regarding potential safety problems of the drug.

Gilead (GILD), the current leader in the next-gen Hep C drugs, is planning a Phase III study with a combination therapy of its NS5A and NS5B inhibitors. The FDA's recent caution regarding NS5 inhibitors might also affect Gilead's sprint toward the finish line. Novartis (NVS), which has recently joined the Hep C crowded waters with the $440m Enanta Pharmaceuticals deal, might also suffer from this new NS5-related safety issues.

About 180 million people worldwide are chronically infected with HCV. The global Hepatitis market was estimated at $6 billion in 2011 and is forecasted to grow to $20 billion until the end of the decade. The combination of this huge and growing market and insufficient efficacy of the current treatments has generated an immense interest among drug developers and quite a few deals.

The recent holdups in the NS5-related treatments suggest that the Hep C pipeline might need some variations. Several companies are developing alternative, non-NS5 inhibitor-related, Hep C treatments. Examples for such technologies are Transgene's (TRGNF.PK) TG4040 - a therapeutic Hep C vaccine based on a virus carrying and expressing three of the major Hepatitis C virus's non-structural proteins (NS3, NS4 and NS5B). TG4040 is currently in a phase II trial.

A different approach is taken by BioLineRx (BLRX) that develops BL-8020, an orally available treatment with a unique mechanism of action - inhibition of Hepatitis C virus-induced autophagy. In other words, BL-8020 acts on the host cell rather than the virus itself, thus greatly differentiating it from current and pipeline Hep C drugs. Preclinical studies have shown a synergistic effect of BL-8020, when combined with other anti-Hep C agents, which is likely to increase these agents' potency and reduce any adverse effects by enabling utilization of lower dosages.

With the current setbacks seen among Hep C pipeline frontrunners, additional rounds of licensing and acquisition deals in this area are expected, and companies that develop new and different approaches for Hep C treatment may greatly benefit from others' failures and should be closely watched by investors that follow this therapeutic field.

Disclosure: I have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours.

Medical Device industry makes a run at Pharma in the HCV space...

Posted 8/9/12 on The OTC Investor.com. Aethlon Medical is serious about it's Hemopurifier, a blood filtration device being looked at for several indications. If it is indeed capable of lowering HCV viral load to a point where pegylated interferon and ribavirin could be more effective and bump up response rates over 50% with less toxicity... and can do so at a cost lower than that of Direct Acting Antiviral combination therapy... Aethlon may be on to something. Yet another reason not to dismiss interferon just yet. 

Bristol’s Halted Hepatitis C Trial Reinforces Aethlon Medical’s Non-Toxic Therapy
By Paul Archie · Thursday, August 9th, 2012

In the biotechnology world, the sun rises and set around the two key words “safety” and “efficacy.”  A serious safety concern last week resulted in Bristol-Myers Squibb (NYSE: BMY) voluntarily halting its ongoing Phase 2 study of BMS-986094, a drug in development as a new indication for hepatitis C as part of the drug maker’s quest for an all-oral regimen for hep C.  A patient who had received a 200 milligram dose of the nucleotide polymerase inhibitor, or “nuke,” suffered heart failure; causing Bristol to stop the trial and begin evaluating participants to determine any correlation between the new drug and the heart damage.

In February, Bristol paid $2.5 billion to acquire Inhibitex, a 163-percent premium to the valuation of Inhibitex at that time, primarily to snag its hepatitis C drug candidate (then called INX-189).  The halted trial could seriously hamper Bristol in its race with Gilead (NASDAQ: GILD) and Abbott Labs (NYSE: ABT) to bring a new hepatitis C drug to market.  It is widely expected that an all-oral drug therapy for the liver disease that affects about 170 million people across the world will generate billions annually in sales.  It is the reason that Bristol paid the premium for Inhibitex and Gilead dished-out $11.1 billion last November to acquire Pharmassets and its hep C drug in development.

Investors that recognize the upside potential of new therapies for hepatitis C should be taking a close look at Aethlon Medical (OTCBB: AEMD), the maker of a first-in-class blood filtration device called the Hemopurifier®.  Recently released clinical research by Aethlon showed that the two most recent hepatitis C-infected patients to receive its Hemopurifier® therapy in combination with the standard of care peginterferon+ribavirin (PR) drug therapy achieved undetectable viral load at day-7.  In lay terms, that means that none of the hepatitis C virus was found in the patients’ bloodstream after seven days of treatment.

As an adjunct, the Aethlon Hemopurifier® selectively targets the rapid clearance of the hepatitis C virus from the entire circulatory system to improve benefit, dose, duration and tolerability of drug therapies.  Drugs, like that of Bristol, Gilead or Abbott, carry substantial safety risks because they are “additive” in nature, meaning that they are putting a foreign substance into the body.  Aethlon’s Hemopurifier® is “subtractive.”  It removes the virus through a proprietary filtering process, which does not carry the same, potentially deadly toxicity risks that can cost major pharma billions to finally realize.

The OTC Investor (http://s.tt/1kpgX)

The Street.com: Rethinking Idenix Pharma in Wake of Bristol's Hep C Blow Up...

Posted 8/6/12 on The Street.com. The Streets's Nathan Sadeghi -Nejad weighs in on the current - and seemingly hyperactive - HCV drug development space. He's right, the last couple of weeks have been a whirlwind of surprises - Novartis giving Idenix the rights to it's HCV drugs back, BMS's BMS-094 seemingly taking it's last breath, Gilead co-formulating it's nuc with it's NS5A inhibitor just to name a few.  BMS has had a rough time of it in the HCV drug development space. It's $885 million purchase of ZymoGenetics with it's Peg Lambda seemed like a great move in 2010, before the advent of the idea of potential interferon-free therapy (I still think Peg Lambda may be a surprise dark horse - I'm still cautious on the potential 'interferon free' except in certain cases), Then consider the $2.5 billion purchase of Inhibitex, whence the doomed BMS-094 nuc came from leaving BMS's NS5A inhibitor without a BMS-owned partner. It's other late-stage HCV drugs aren't much to sneeze at. Ouch. Sadeghi-Nejad makes some other observations (Gilead - yes. Idenix - nuc is too close to BMS-094, maybe a toxicity issue but no safety signals to support. Vertex nuc looks powerful, but too far from market to mean much) that you may or may not agree with. Definitely a good read if you're watching the HCV drug development race.

Rethinking Idenix Pharma in Wake of Bristol's Hep C Blow Up

By Nathan Sadeghi-Nejad - 08/06/12 - 7:00 AM EDT
Tickers in this article: IDIX BMY GILD VRTX

NEW YORK (TheStreet) -- Last week, Bristol-Myers Squibb(BMY) confirmed my previously reported suspicions by abruptly halting a Phase II trial of BMS-094 (formerly INX-189) -- a nucleotide polymerase inhibitor, or "nuc," for the treatment of hepatitis C. One patient in the study experienced major cardiovascular toxicity, forcing Bristol-Myers to stop dosing BMS-094.

The company has provided few follow-up details but it appears as if BMS-094 is dead.

That means Bristol-Myers' $2.5 billion acquisition of Inhibitex (from where BMS-094 originated) has proven to be a complete zero in less than seven months. I'm not sure if that's a mergers-and-acquisition disaster record, but it's probably close.

The demise of BMS-094 has also reshaped the Hep C landscape. Let's review who still stands and where. For some assistance, I turned to John Tucker, a scientific analyst with BioMedTracker, a division of Sagient Research. Tucker recently published an excellent overview on Hep C drugs in development and he's been all over BMS-094 and its implications.

At this point, combining a "nuc" with an NS5A inhibitor and the generic antiviral drug ribavirin seems to be the most promising "all oral" Hep C regimen in clinical development. This makes Bristol-Myers' daclatasvir, an NS5A inhibitor essentially useless on its own. The company's other later-stage hep C drug candidates -- the non-nucleoside polymerase inhibitor BMS-791325 and the protease inhibitor asunaprevir -- have only modest efficacy or toxicity issues, or both.

Bristol-Myers may continue to beg but I'm convinced Gilead Sciences(GILD) has no interest in a daclatasvir partnership. As I noted recently, Gilead's nuc-NS5A combination -- GS-7977 and GS-5885 -- has made rapid clinical progress and will start pivotal trials this year. In sum, the BMS-094 blowup leaves Bristol-Myers up a proverbial creek in Hep C. Although this failure has little long-term financial impact, Bristol-Myers' apparent inability to foresee this compound's risks raises concerns about the company's R&D and business development capabilities.

Gilead emerges a big winner. I have long believed Gilead would be first to market with an all-oral Hep C regimen, but Bristol-Myers has handed the company a much bigger lead. (I also still doubt the size of the commercial market for Hep C, but that's another issue.)

I initially considered Idenix Pharmaceuticals(IDIX) and its nuc IDX-184 a winner emerging from the BMS-094 blowup. Now, I'm less sure.

IDX-184 has a chemical structure that is similar to both BMS-094 and Pharmasset's PSI-938, another Hep C nuc that was killed off by toxicity problems last year. More specifically, the active moiety of IDX-184 -- the part of the molecule that makes the drug work -- appears to be similar to the active moieties of both BMS-094 and PSI-938. That could be a big problem.

Chemists often attach nonessential atoms to a drug candidate in an attempt to change the compound's overall physiological behavior. As the drug is metabolized in the body, those byproducts are cleaved and the working core of the drug -- the active moiety -- is unveiled.

The byproducts are usually innocuous, but not always. For example, it's not clear whether the side effects that killed BMS-094 were caused by the active moiety or by 1-naphthol, a toxic metabolite of the drug. Similarly, PSI-938's fatal flaw remains unclear. This worries me, and it should worry Idenix bulls.

Idenix does have a very reasonable defense. Management contends IDX-184 is nearly entirely targeted to the liver and metabolized poorly in other cell types. Further, IDX-184 seems to be more slowly metabolized by the liver than BMS-094. These factors certainly lessen the risk of toxicity. Thus far, Idenix has treated roughly 60 patients for 12 weeks with IDX-184 and observed no safety signals, including no cardiovascular side effects.

That's encouraging, but I would prefer to overpay for Idenix after there are more data on IDX-184. I would reduce or eliminate long exposure to Idenix until the drug's safety has been more completely established.

Two more Idenix red flags that make me cautious: First, Novartis(NVS), Idenix's partner for nearly a decade, ended the relationship last week. I understand that Novartis wasn't much of a collaborator so walking away might actually be a net positive for Idenix. But I still tend to view pharma-biotech breakups as a negative, although in this case a bit less so.

Second, Idenix completed a major secondary offering only two days after the Novartis breakup. Idenix sold 22 million shares at $8.00 per share or 28% below recent highs. Although I generally support equity issuances at management's discretion, the company still had at least $90 million in the bank. Shareholders should feel justifiably frustrated at this seemingly unnecessary rush dilution of the existing investor base. I worry that the timing signals dark clouds on the horizon.

Right before the Bristol-Myers news, Vertex Pharmaceuticals(VRTX) announced impressive early clinical data for ALS-2200, a nucleotide analogue licensed from Alios BioPharma. After seven days of dosing, the eight treated patients showed a median 4.54 log reduction in viral load. That's near complete eradication of virus, for those of you unfamiliar with the logarithmic scale.

Unfortunately for Vertex, ALS-2200 has not cleared any meaningful long-term safety hurdles and the drug remains years behind Gilead's compounds. I would put Vertex on the "watch and wait" list, but that's it.

As I have discussed before, it's hard for me to get excited about the other Hep C players. Abbott(ABT) has a seemingly decent trio of drug candidates in later-stage development, but the impending spin off of AbbVie -- Abbott's pharma business -- makes the new company nearly completely dependent on the multi-blockbuster rheumatoid arthritis drug Humira.

Johnson & Johnson's(JNJ) TMC-435 looks solid but lacks an obvious companion unless the company partners with Gilead or physicians, on their own, decide to combine TMC-435 with Gilead's GS-7977 into an "off label" all-oral Hep C regimen -- an idea that BioMedTracker's Tucker believes is a real possibility. Finally, everyone wants me to like Achillion Pharmaceuticals, but there is no shortage of NS5A or protease inhibitors -- the company has two NS5As and a protease inhibitor -- so I can't get that excited.

Ironically given the longstanding investor skepticism, Gilead appears likely to dominate the Hep C market over the next decade. I still worry the company vastly overpaid for Pharmasset, but that concern will be meaningful only if something goes wrong and investors are looking for a cudgel with which to beat management. Otherwise, it's time for investors to start thinking logically about the real size of the Hep C treatment market. It's going to be hard for any company to make big money if there aren't enough Hep C patients to treat.

Disclosure: Sadeghi has no positions in any of the stocks mentioned in this article.

Barclays analyst on GILEAD and IDENIX....

Original article posted on StreetInsider.com 2/10/12 - This is an article a good friend pointed out to me earlier today. If a combo of one nucleoside inhibitor and ribavirin can become a dominant therapy type for HCV - a virus notorious for excessively high, error-prone replication and an uncanny ability to evade the host immune system - then I'm in.  To my mind however, that's either excessively positive thinking or a typo.


Barclays on U.S. Pharma: A New Era for Hep C Therapy - Starts Coverage on GILD & IDIX

Analyst, C. Anthony Butler, said, "The race towards developing the second-generation of direct antivirals (DAAs) may be a dead-heat. By the end of this decade, we believe two dominant therapy types will emerge for hepatitis C (HCV) patients: 1) a combination of a nucleotide polymerase inhibitor (Nuc) and ribavirin; and 2) a cocktail of a nucleotide polymerase inhibitor and one or two DAAs of other mechanisms."

"GILD has leapfrogged competitors through the bold acquisition of Pharmasset, and its stock move (+32.7% YTD vs NASDAQ +11.8%) reflects the market sentiment that GILD is leading the HCV race. We estimate that GILD could capture ~40% of the US HCV market by 2020 and US sales would peak at $2.8B in 2017."

"IDIX needs to find a home for its Nuc IDX184 in order to remain a contender."

Currently, shares of IDIX are trading down 1.25% and shares of GILD are flat on the session.