Achillion Pharmaceuticals HCV pipeline suddenly looking attractive...

Posted 8/29/12 on Business Week.com. Achillion Pharmaceuticals, once regarded as an also ran by Big Pharma suddenly looks sexy again as clinical holds and pipeline failures stymie drug development with Idenix and BMS. Rumors of a takeover has made Achillion stock surge in the past couple of days. The HCV drug development space continues to be one of the most dynamic in pharma, there is definitely no shortage of spills and thrills. 

Achillion Deal Looming as Hepatitis Drugs Fail: Real M&A

By Ryan Flinn and Will Robinson on August 29, 2012

Achillion Pharmaceuticals Inc. (ACHN), the developer of hepatitis C treatments that was passed over by potential acquirers in the last year, is poised to draw renewed interest after setbacks by rival drugmakers.

Bristol-Myers Squibb Co. (BMY) last week said it was abandoning an experimental hepatitis C pill it obtained through its February purchase of Inhibitex Inc. after one patient died and others were hospitalized while taking the drug in a study. This week, Idenix Pharmaceuticals Inc. said U.S. regulators halted its study of a similar therapy, marking the second hold on clinical trials for the company this month.

With the market for new hepatitis C treatments projected to reach $20 billion by 2020 and Achillion facing no delays in two drugs under development, Piper Jaffray Cos. and William Blair & Co. say the $481 million company could gain fresh attention as a takeover candidate for Merck & Co. (MRK), Roche (ROG) Holding AG and Vertex Pharmaceuticals Inc. (VRTX) A suitor could pay a premium of as much as 79 percent to Achillion’s stock price and still acquire the New Haven, Connecticut-based company for less than its peak market value earlier this year, when takeovers and merger speculation spurred a surge in hepatitis C drugmakers’ shares.

“The frenzy has been taken out of the space, but I still think Achillion is very attractive” because its therapies have the potential to be the best of their type, Ted Tenthoff, a New York-based analyst for Piper Jaffray, said in a telephone interview. “We expect the wave of consolidation to continue. Achillion is clearly a target.”

Drug Development
Joe Truitt, Achillion’s chief commercial officer, said it wasn’t appropriate to comment on the company’s development plans, including the possibility of a takeover.

“We’ll make the best strategic options as they come to us, but for right now, we’re developing our drugs and getting them into combinations and making them available to patients,” Truitt said in a phone interview.

Today, shares of Achillion rose 3.5 percent to $6.86 at 9:45 a.m. in New York, the second-biggest gain among 116 stocks in the Nasdaq Biotechnology Index.

Hepatitis C is a viral infection that can cause liver damage and is estimated to affect 180 million people worldwide, according to the National Institutes of Health. Rising deaths among so-called baby boomers from the infection prompted U.S. health officials to declare in May that all of those born from 1946 to 1964 are at risk and should be tested.

Achillion is among several companies racing to develop hepatitis C cures that would replace the standard year-long injectable treatment that can cause flu-like symptoms.

Four Classes
There are four new classes of drugs under development to cure hepatitis C. Each work in different ways to stop the virus from replicating, and can be effective against one or several subtypes of the disease.

Drugmakers such as Abbott Laboratories (ABT), Achillion, Bristol- Myers, Gilead Sciences Inc. (GILD), Merck and Vertex have been testing these therapies, either alone or together, with varying degrees of success. The promise of a market that Achillion Chief Executive Officer Michael Kishbauch estimates will grow to $20 billion by 2020 spurred at least three acquisitions since October.

The biggest deal was Gilead’s $10.8 billion acquisition of Pharmasset Inc., announced in November, which came a month after Roche agreed to buy Anadys Pharmaceuticals Inc. for about $230 million. Bristol-Myers followed in January by announcing its $2.5 billion purchase of Inhibitex.

Fresh Look
Achillion’s Kishbauch said in November that the company was in “advanced discussions” with potential partners or acquirers. Its shares then reached a five-year high of $12.38 in February on takeover speculation before falling (ACHN) 46 percent since then as no deal materialized.

Now, with Bristol-Myers stopping development of the drug it bought from Inhibitex, and Idenix (IDIX) halting testing of a similar therapy, Achillion could attract a fresh look from companies seeking hepatitis treatments to use on their own or in combination with their existing therapies, said Liisa Bayko, a Chicago-based analyst with JMP Securities LLC.

Achillion is testing two types of drugs. By combining several classes of these new hepatitis C drugs, doctors may be able to limit the virus’ ability to infect, mimicking the strategy that a decade earlier helped turn HIV from a killer disease to a controlled one.

During the first quarter, Achillion will be reporting on how effective its two therapies work in combination. Good data could entice competitors to bid, Bayko said.

‘Well-Positioned’
“By the first quarter of next year, we could be a very different company,” Achillion’s Truitt said. “If that combination data comes through, then we really have a commercially viable, competitive combination that will put everybody on notice.”

“We’re pretty optimistic for Achillion,” Bayko said in a phone interview. “They’ll be well-positioned to be a candidate to be taken out, because right now, there are very few options if you want to get involved in hep C, in terms of combinations that are more advanced that are still in clinical development.”

Bayko said that while she expects a suitor to wait for the data on the drugs before making an offer, Achillion still could fetch as much as $10 a share if a company bid for it now, 51 percent more than its closing price yesterday.

Piper Jaffray’s Tenthoff said Achillion could lure suitors such as Merck, Roche and Vertex as they seek to compete against Gilead, which is seen by analysts as having the most promising hepatitis C drug. Gilead is poised to start testing two of its therapies together in a single pill this year, putting it on track to request U.S. regulatory approval for the drug in 2014.

Gilead Bid
Ronald Rogers, a spokesman for Merck, said the company doesn’t comment on speculation when asked whether the Whitehouse Station, New Jersey-based drugmaker was interested in Achillion, while an e-mail to Basel, Switzerland-based Roche’s media relations office wasn’t returned. Megan Pace, a spokeswoman for Cambridge, Massachusetts-based Vertex, declined to comment.

Even Gilead could seek to acquire Achillion as a way to remove a potential competitor and bolster its position, said Peter Kolchinsky, co-founder and general partner at RA Capital Management LLC, which oversees $300 million, including Achillion shares.

“Gilead could solidify its supremacy if it had Achillion’s drugs, each best in its respective class based on what we know so far,” Kolchinsky said in an interview. “Acquiring Achillion would also be a wise defensive move for Gilead, keeping it from falling into a competitor’s hands or from becoming an independent low-cost competitor.”

Safety Concerns
Cara Miller, a spokeswoman for Foster City, California- based Gilead, said the company (GILD) doesn’t comment on market speculation.

Brian Skorney, an analyst with Brean Murray Carret & Co. in New York, says Achillion won’t be a takeover target soon because it has “a lot more to prove” with clinical data next year. Other companies that developed hepatitis C treatments like Pharmasset and Inhibitex proved their drugs were effective before they were bought, and the only remaining question about their products was safety, he said.

The safety problems that challenged the drug Bristol-Myers bought from Inhibitex and the regulatory holds that Idenix faces show how much risk is still left in the market for hepatitis C treatments, said Les Funtleyder, a fund manager focused on the health-care industry at New York-based Poliwogg.

“What’s that phrase, ‘Once burned, twice shy?’” Funtleyder said in a phone call. “If someone was to repeat what happened to Bristol, shareholders would start to ask questions about management’s judgment.”

Cheaper Now
Still, after the drop in Achillion’s stock this year, a buyer would be taking on the risk of the therapies potentially failing at a lower price tag.

During the past 12 months, acquirers that announced deals for biomedical companies paid 65 percent more than the target’s average 20-day stock price in transactions greater than $500 million, according to data compiled by Bloomberg. A bidder for Achillion could offer a premium of as much 79 percent to yesterday’s stock price and still get the drugmaker for less than its record market value of $863 million in February.

The market for treating the viral infection is too big to be dominated by Gilead alone, so large drugmakers may have the appetite to acquire a company such as Idenix or Achillion once they produce sufficient data on the safety and effectiveness of their drugs, said Y. Katherine Xu, a New York-based analyst at William Blair. Kelly Barry, a spokeswoman for Cambridge, Massachusetts-based Idenix, didn’t return a voicemail message and e-mail sent after business hours about whether the company has been approached by suitors.

“Both Idenix and Achillion, their strategy is to sell themselves,” Xu said. “Timeline-wise, these two used to be similar, but now Achillion may be a little bit ahead.”

To contact the reporters on this story: Ryan Flinn in San Francisco at rflinn@bloomberg.net; Will Robinson in New York at wrobinson11@bloomberg.net.

To contact the editors responsible for this story: Sarah Rabil at srabil@bloomberg.net; Reg Gale at rgale5@bloomberg.net.

Merck and Codex go "green" with new production process for Victrelis...

Article posted 4/10/12 on InPharm.com - Pressures on price continue to increase and with large patent expirations on the horizon, what's a Big Pharma company to do to maintain shareholder-friendly profitability levels?? One answer is to create better efficientcies in the drug production process, thereby dropping the price and (hopefully) creating bigger margins. And if you can do it 'green', well, that's some corporate goodwill for you.   Merck has teamed up with catalyst Codexis to develop a more efficient production process for Merck's HCV protease inhibitor, Victrelis. Codexis fits into a very interesting niche that will certainly maintain appeal to drug manufacturers as the pressure to drop prices increases. Definitely a niche I'm going to make an effort to watch in the coming years. 

Codexis and Merck develop green Victrelis production

Published on 10/04/12 at 12:23pm

Merck has teamed up with catalyst specialist Codexis to develop a more efficient manufacturing process for recently-approved hepatitis C treatment Victrelis.

Merck was granted approval for NS3/4A protease inhibitor Victrelis (boceprevir) in the US last May and in Europe the following July.

Sales of the product have quickly ramped up to reach nearly $90 million in the fourth quarter of 2011 and $140 million for the full year, despite being available only in a handful of markets.

Analysts have tipped Victrelis as a future blockbuster, and Merck has enlisted the aid of Codexis to make the production process more efficient and boost its profit margin for the drug at a time when the firm is facing patent expiries on some key product lines.

Merck and Codexis scientists developed an enzyme-based production method for a key intermediate in the production of boceprevir that has been recently published in the Journal of the American Chemical Society (JACS).

The JACS publication describes the creation and characterisation of a biocatalyst that was capable of performing a key step in the synthesis of boceprevir.

The new method increased chemical intermediate yield 150% over the previous process, according to the paper. Moreover, it reduced raw material use by 60%, water use by 61% and overall process waste by 63%, making the manufacturing process greener.

"Incorporation of innovative environmentally sustainable means of manufacture is a key aspect of our research and development strategy," commented Richard Tillyer, senior vice president for Discovery and Preclinical Sciences at Merck Research Laboratories.

"Enzymatic based methods can offer a biodegradable and renewable alternative to currently employed methods."

Biocatalysts - generally based on enzymes - have been used on a small scale in the pharmaceutical industry for many years, but it is only in the last few years that they have migrated into the commercial-scale manufacturing environment.

Pressures on the profitability of drugmakers have encouraged the industry to cut costs and boost efficiencies across the board, including in manufacturing, and Codexis has tapped into that trend.

Last year the company reported sales growth of 16% to $124 million that it said was "driven by increased sales to both generic and innovator pharmaceutical customers".

Phil Taylor

Seeking Alpha - Achillion Pharmaceuticals: Hope, Hype, And Hep C

An article appearing 3/27/12 by Stephen Simpson on Seeking Alpha.com - one of the more level-headed articles appearing on that particular site in recent months, IMO (admittedly, coming from me, that might not mean much!). It's very hard to be prescient in regards to Achillion's future in HCV, but with a wholly-owned, advancing pipeline diversified among viral targets, it has to be considered at least somewhat of a target of companies like Merck, J&J and Vertex that need to fill holes in their pipeline or need compounds with synergistic activity. Mr. Simpson also gives a quick rundown of what's happening in the HCV drug development marketplace as well as some apocryphal statistics on HCV infection within South America that could feasibly boost the value of the HCV market considerably by 2016 over current thinking, in his estimation.   


Achillion Pharmaceuticals: Hope, Hype, And Hep C

By Stephen Simpson - Seeking Alpha

I've followed biotech for a long time now, and I have a hard time thinking of an example of another addressable market like hepatitis C (HCV) where investor interest has just exploded in the space of about a year. Like antisense, monoclonal antibodies, RNAi, genomics, stem cells and every other hot property in biotech, there has been no end of hope, hype, and hucksterism. Although HCV is likely to grow into a very financially significant drug target in the coming years, it's worth wondering just how much of the frenzy today can be justified in long-term valuations.

In particular, I'm curious about Achillion Pharmaceuticals (ACHN) these days. I've watched this stock for a while now and came close to buying on multiple times in the pre-2010 pre-$2 level. I underestimated just how fast this market would heat up, though, and had to re-learn a painful lesson - sometimes, you snooze and you lose.

Achillion jumps out as the only serious HCV play I'm aware of with a market cap below $1 billion (while Idenix (IDIX) is hardly a giant at $1.1 billion). Not only is it relatively small, but it also may be one of the relatively few players with its own home-grown effective combination therapy.

Of course everything Achillion is working on in HCV is still in the clinic and as Gilead (GILD) showed so clearly recently, "surprising" clinical results are not always positive surprises. The end result, then, is that this may be the next Pharmasset or just another biotech destined to flame out.

The Good - Interesting Compounds All Their Own

Achillion has at least two HCV antivirals well worth watching - ACH-1625 and ACH-3102.

ACH-1625 is a potentially pangenotypical NS3 protease inhibitor (PI) that has shown both solid efficacy and encouraging safety in early studies. Showing both strong efficacy and safety thus far, it could perhaps be the backbone for future combination therapies. That said, pangenotypical efficacy is not yet established and the compound still has not gone through a pivotal Phase 3 study.

The good news with antivirals is that, unlikely oncology and anti-inflammatory drugs, efficacy signals in early pilot studies often hold up through pivotal studies. What's more, these studies are relatively easy to enroll and can be completed expeditiously. What that all means for investors is that ACH-1625 could have a relatively quick path to market.

Achillion is also developing ACH-3102, a NS5a inhibitor, and expects to put it in human studies soon. This drug looks like it should be less subject to resistance and the company (as well as bulls) seem more excited about this drug than the more advanced ACH-2928 (also a NS5a inhibitor). Coupled with ACH-1625, this could be a very interesting combo therapy, but it's worth mentioning that almost every drug is interesting to bulls going into Phase 2 studies.

These aren't the only drugs in Achillion's HCV pipeline, and the company does have identified experimental compounds targeting bacterial infections and HIV. It should be noted too that Achillion's HCV pipeline is wholly-owned.

The Bad - Competition, And Expectations, Left Right And Center

Achillion is very definitely not going to be the first company to market with new HCV drugs, and there is apt to be extensive competition in the market. That is not only going to place a premium on the SVR efficacy data and safety profile, but also potentially on the marketing muscle of the company in question.

Since its acquisition of Pharmasset, Gilead was put in the pole position in the race to develop blockbuster HCV drugs. That is, until the company reported Phase 2 data on the superstar-to-be '7977 that showed it is not 100% perfect. Specifically, this Phase 2 study indicated that '7977 may not be effective in null responders (patients who have failed to respond to earlier treatments), and may give new hope to alternate approaches that include a NS5a inhibitor or NS3 protease inhibitor.

That said, a little perspective is in order. Maybe '7977 isn't flawless, but SVR-12 rates of 91% in genotype 1 and 100% in genotypes 2 and 3 in a thus far safe drug is still pretty impressive. Moreover, Gilead is looking at a variety of combination possibilities and while the company would certainly love to have "the one antiviral to rule them all", being a part of a blockbuster combination therapy is not a bad consolation prize.

Along Gilead and Achillion is a host of companies developing therapies and a sea of drugs known more by number than by name.

Bristol-Myers Squibb (BMY) has its NS5a inhibitor daclatasvir well along in studies, a PI ('032), and the NS5b inhibitor it acquired with the Inhibitex deal, as well as other earlier stage compounds. The NS5a inhibitor has shown solid efficacy, and its PI/NS5 combo showed 100% SVR without PEG-interferon or ribavarin.

Of course there are many more. Abbott (ABT) has its own all-oral combination (NS5a and PI), as does Roche (RHHBY.PK), although the efficacy in the Roche compounds has not been as encouraging. Johnson & Johnson (JNJ) has its TMC435 PI that it in-licensed from Medivir, and Boeringher Ingelheim has its PI as well. Indenix has a nucleotide inhibitor and NS5a inhibitor in trials and a non-nuc in preclinical development.

Last and not least are Vertex (VRTX) and Merck (MRK). These companies have brought the two newest HCV drugs to market (Incivek and Victrelis, respectively). Vertex has a PI in trials and two nucleotide inhibitors licensed in from Alios, while Merck's PI has seen a significant setback tied to safety issues.

A Quick Rundown On The Market, Prospects, And Deals

The oft-repeated statistic on HCV says that there are between 130 million and 170 million infected persons around the world. Approximately 4 million of those are in the U.S., with another 5 million the EU. By way of comparison, Brazil is thought to have at least 7 million HCV patients, India at least 10 million, and China 43 million.

Untreated HCV offer leads to severe chronic liver disease (including cirrhosis), but the long-used PEG-interferon and ribavirin therapy (dominated by Roche and Merck) has had success rates of below 50% in long-term usage.

That efficacy underlies a lot of the market expectation on HCV drugs. While the pre-Incivek/Victrelis HCV market was estimated to be about $3 billion (with $2.5 billion of that going to PEG-inteferon), analysts believe better efficacy could drive that figure close to $10 billion in 2016.

Admittedly, that's a large number. It may not be completely out of line, though, if these 90%+ SVR rates hold up in pivotal studies. Offer people with a serious lifelong illness a safer, more effective drug that is also easier to take and you can almost always charge a premium for it. Also, think about it this way - the U.S. and European insurance/payer systems are willing to pay several tens of thousands of dollars for cancer therapies that offer a few extra months of median survival benefit, so there's clearly a willingness to pay for better clinical outcomes.

What's this all mean for Achillion?

I could see ACH-1625 garnering perhaps up to a billion in sales if the early results hold all the way through studies. Moreover, there's the potential to be had from the combo therapy; whether that's in combination with another Achillion drug or a rival compound (like, say, Gilead's '7977). If Achillion could garner $1 billion in sales, that would translate into a fair value of $13 to $18 per share today based upon your forward multiple estimate (6x or 8x).

I'm sure $1 billion in sales will sound too small to Achillion bulls. Fair enough; if the early results hold up, maybe it's an even bigger blockbuster, but it looks like there are going to be a lot of competing therapies on the market and good marketing is going to deliver sales even in inferior compounds.

It may well be the case, though, that Achillion never makes it to the point where its sales matter. I would be quite surprised to see Achillion partner its drugs, but I think a buyout could well happen. Certainly there have been plenty of chatter on that subject, what with Gilead and Bristol-Myers paying up for HCV compounds (and Roche also making some deals of its own).

So how does the M&A scene break out? I don't think Bristol-Myers would need Achillion, and I don't think Gilead would go that route either unless a '7977/ACH-1625 really showed something special. Johnson & Johnson may think it needs non-PI partner compounds and may not want to pay for the overlap between their PI programs.

That said, I think there are a lot of names left that could be interested. Merck arguably needs a better protease inhibitor, and likewise Roche, Abbott, and Vertex may find that they need better compounds than they presently have. Companies like Sanofi (SNY) and GlaxoSmithKline (GSK) aren't doing much here today, but could find Achillion to be a ready-made HCV platform. Odds are, though, that Achillion holds out a bit for a desperate buyer - not because there's anything wrong with its pipeline, but because a desperate Merck or Roche may pony up a better deal if they feel pressure.

The Bottom Line

Taking a midpoint of that earlier $13-$18 range, I'd say Achillion may be worth about $15.50 a share today. Annoyingly, that's almost spot on with the current consensus number. I do believe there could be more upside as its pipeline matures and rivals run into problems, but I usually want more than 50% undervaluation before buying into a new biotech story.

Disclosure: I am long RHHBY.PK

The Street.com: EASL Gives Wall Street's Privileged Investors Sneaky Preview to Key Hep C Data

Article posted on The Street.com on 3/20/12. Spring is in the air, and that means that one of the most important meetings in HCV drug development - EASL - is right around the corner.  The Street author Adam Feuerstein is none too pleased on EASL's rather elitist approach to disseminating important data ahead of time to only a chosen, privileged few. He's right - and he's also right that EASL's attempt at keeping this data embargoed until the actual start of the conference is pert near impossible.  The time has come for reform and revolution. I'd be right there on the front lines, but there's too much good stuff on TV. 

EASL Gives Wall Street's Privileged Investors Sneaky Preview to Key Hep C Data

By Adam Feuerstein    03/20/12 - 10:45 AM

Update: After this column was published, EASL announced a delay in the release of research abstracts for the International Liver Congress to Tues. March 27.

BARCELONA (TheStreet) -- Investing in hepatitis C drug stocks is a suckers bet this week because the European Association for the Study of the Liver, better known as EASL, has rigged the game so that Wall Street's privileged investors get a sneak peek at new clinical data ahead of an important and closely followed conference next month.

EASL's International Liver Congress, taking place April 18-22 in Barcelona, is the must-follow medical meeting of the spring. Gilead Sciences, Bristol-Myers Squibb, Abbott, Idenix Pharmaceuticals, Vertex Pharmaceuticals and Merck are among the companies rolling out new clinical data on experimental hepatitis C therapies.

But if you want an advance look at potentially market-moving hepatitis C drug data, you'll have to be an EASL member or a registered attendee of the EASL meeting -- a group which includes hedge fund and mutual fund portfolio managers and sell-side analysts, all of whom can pay for early access.

EASL plans to selectively distribute hepatitis C drug research abstracts to these folks on Thursday. The same documents will not be made available to the public. That means a select group of investors will have access to potentially stock-moving clinical data while a majority of investors will be kept in the dark.

Journalists registered to cover the EASL meeting will also be granted early access to hepatitis C research abstracts but they are barred by EASL's restrictive embargo rules from writing about any new data until the start of the April meeting.

EASL's abstract distribution policy is misguided, unfair and quite frankly unworkable. Smarter medical and scientific groups like the American Society of Clinical Oncology (ASCO) realized years ago that trying to compartmentalize research abstracts was futile. Information cannot be selectivity disclosed and expected not to leak, especially information that will weigh on the market valuations of biotech and drug firms involved in new hepatitis C drug research.

That's why most medical and scientific groups made research abstracts freely available to everyone in advance of major conferences.

Jacqui Sisto, an EASL spokesperson, explained via email that selective disclosure of research abstracts "ensures the integrity of the International Liver Congress." Really? EASL appears to be corrupting its most important meeting, not making it more honest.

The Motley Fool takes on universal testing for HCV...

Article posted on 3/16/12 on Motley Fool.com. The Motley Fool's Brian Orelli, Ph.D on the economics of universal testing for HCV. He makes the case that drug companies should leverage public policy to uncover as many potential patients as possible. What Dr. Orelli missed is that every HCV drug development company with skin in the game is already doing that through the Viral Hepatitis Action Coalition. A good read anyway.

Hep C Drugmakers' Best Outcome


By Brian Orelli, PhD

March 16, 2012

Treating hepatitis C is a losing proposition. Unlike treatments for chronic diseases -- high blood pressure or diabetes, for instance -- if a hepatitis C drug does its job, the patient is cured. It's a one-and-done treatment. Since the hepatitis C epidemic peaked many years ago, hepatitis C drugmakers need to find a new source of patients.

A report published in Clinical Infectious Diseases might have the solution: people who are already infected, but don't know it yet.

Current guidelines recommend testing only people who have identified risk factors such as drug use, blood transfusions before blood-bank testing began in 1992, or unexplained liver-function abnormalities, for example -- but that misses a substantial number of infected individuals. Estimates vary, but somewhere between 50% and 75% of people infected with hepatitis C don't know it.

Most probably have the risk factors, but they're unwilling to admit to the drug use, especially if it was years ago, or have forgotten about the blood infusion. Or the doctors aren't asking the right questions to identify the risk factors -- it's a touchy subject, you know.

The solution: Test everyone. You'll get a lot of negative results -- less than 2% of the population is infected -- but you'll catch those who might not have been diagnosed before they progress to serious liver problems.

The researchers plugged everything from costs to cure rates to likelihood of progression of liver disease and a lot of additional parameters into one giant formula and concluded that it would be cost-effective to screen everyone between the age of 20 and 69. Hepatitis C leads to liver cancer and other complications, and eliminating the cost of a liver transplant -- a quarter-of-a-million-dollar procedure -- can make up for a lot of $20 tests.

Sounds good, in theory

One journal article isn't going to change public policy; that will require a recommendation from the Centers for Disease Control and Prevention, which is a slow and methodical process.

If the CDC does institute universal testing for adults, hepatitis C test makers would certainly benefit. Just keep in mind that there's substantial competition out there: Abbott Labs (NYSE: ABT ) , Roche, Siemens, and OraSure Technologies (Nasdaq: OSUR ) all sell hepatitis C tests. They don't disclose margins on individual tests, but considering the number of players involved, I'd have to guess they aren't great.

Drugmakers developing hepatitis C treatments will be the real beneficiaries if more people are diagnosed. With the cost of treatment in the $80,000 range, each new patient is quite valuable.

That is, if they're treated
As the authors of the paper point out, screening is cost-effective -- and makes drugmakers money -- only if the patients who test positive are actually treated. Hepatitis C is a chronic infection that takes years to do any real damage in patients. Unlike cancer, where there's an immediate need for treatment, hepatitis C patients can take their time.

That could mean patients are lost to follow-up. It could also mean patients wait until drugs go off patent and there are cheap generics available before taking the drugs.

Identifying more patients is good, but they're not going to be moneymakers without the help of doctors.

Something companies can control
The cure rate of hepatitis C drugs is one of the factors that determine whether testing is worth the effort. If there were no way to treat patients, identifying infected patients would be only marginally useful.

As it is, Vertex Pharmaceuticals' (Nasdaq: VRTX ) Incivek has increased the standard of care substantially. Roche's Pegasys and Merck's (NYSE: MRK ) Pegintron cure about half of the patients, while adding Incivek increases that to around 70%.

As Gilead Sciences (Nasdaq: GILD ) , Abbott, and others develop better drugs, and we get closer to 100% cure rates, the benefit of testing will increase. It would be nice to have the patients waiting when the second-round of oral medications are approved, but drugmakers might have to get the drugs approved first and then show that identifying additional patients is beneficial.

Okairos AG begins mid-stage trial of preventative vaccine for HCV...

Posted 3/14/12 via Bloomberg.com .  Swiss company Okairos AG begins mid-stage trial looking a what it hopes to be the first preventative vaccine for the Hepatitis C virus. 

Former Merck Unit Works on First Vaccine for Hepatitis C
By Makiko Kitamura - Mar 14, 2012 1:00 AM PT

Okairos AG, a biotechnology business that Merck & Co. (MRK) sold to venture capital funds in 2007, is seeking to produce the first preventive vaccine for hepatitis C, challenging makers of treatments for the disease.

Okairos has begun a mid-stage study, funded by the U.S. National Institutes of Health, of a gene-based vaccine designed to stimulate the body’s immune system to prevent hepatitis C from taking hold, Chief Operating Officer Tom Woiwode said in a phone interview from the company’s Basel, Switzerland, headquarters.

No vaccine exists for hepatitis C, which affects as many as 170 million people globally, putting them at risk of developing liver cancer, according to the World Health Organization. The growing population of patients infected with the virus spurred Gilead Sciences Inc. (GILD)’s decision in November to buy experimental hepatitis C-treatment maker Pharmasset Inc. for $10.8 billion and Bristol-Myers Squibb Co. (BMY)’s acquisition in February of Inhibitex Inc. for $2.5 billion.

“This could change the landscape quite a bit,” said Les Funtleyder, a health-care strategist and portfolio manager at Miller Tabak & Co. in New York. “In theory, if you could vaccinate everyone, you’d need a lot less drug.” Funtleyder said he isn’t aware of any other preventive vaccines in development.
Disease Transmission

Okairos’s vaccine would target those who may be at risk of infection. The disease is most commonly transmitted through contaminated blood transfusions, organ transplants, contaminated syringes and needle-injected drug use, according to the WHO.

Most preventive vaccines stimulate the production of antibodies, molecules produced by the immune system as part of the body’s defenses. Development of Okarios’s vaccine was triggered by studies of patients with early-stage hepatitis C, of whom about 20 percent spontaneously clear the virus and avoid advancing to the chronic phase, Woiwode said.

Researchers have found those patients tend to have a strong response in the blood’s T cells, Woiwode said. Armed with that knowledge, Okairos developed technology that delivers genetic material to stimulate T cells, the white blood cells that help the body fight diseases.

This approach contrasts with most other vaccines, which stimulate an antibody response, Woiwode said.

“We’ve opened up a new path that will allow us to address a number of diseases, hepatitis C being the first one,” he said in the interview yesterday.

Even if a vaccine is approved, medicines are needed to treat patients already infected, Miller Tabak’s Funtleyder said.

Industry Projects
Merck and Vertex Pharmaceuticals Inc. (VRTX) won approval last year for the first new therapies for hepatitis C in almost a decade. Johnson & Johnson (JNJ), a partner in the Vertex drug, is also cooperating with Swedish drugmaker Medivir AB (MVIRB) on a hepatitis treatment. Basel-based Roche Holding AG (ROG) agreed in October to buy Anadys Pharmaceuticals Inc., another maker of experimental medicines for hepatitis C, for about $230 million.

Profectus Biosciences Inc., a Baltimore-based vaccine manufacturer, is also developing a drug that prevents patients with early-stage hepatitis C from advancing to the chronic stage. The company plans clinical trials of the product in 2013.

Investors in Okairos, which is also developing malaria, cancer and flu vaccines, include Boehringer Ingelheim Venture Fund, Life Sciences Partners, Novartis Venture Funds and Versant Ventures. The Swiss company has also received grants from the European Union and the Bill and Melinda Gates Foundation.

The company is in discussions with potential partners for marketing the vaccine, Woiwode said.

“I have no doubt that if this Phase 2 study is successful, there will be no shortage of interest to work with us to bring this to the market globally,” he said.
To contact the reporter on this story: Makiko Kitamura in London at mkitamura1@bloomberg.net

To contact the editor responsible for this story: Phil Serafino at pserafino@bloomberg.net

Original article: The REAL drug to beat in Hepatitis C treatment: Ribavirin

An article I authored and recently published online thanks to the great folks at GastroHep.tv, a multi-media, cutting edge online resource for the Gastroenterology and Hepatology community. 



The REAL Drug to Beat in Treating Hepatitis C: Ribavirin

by Chris Barnes

By now, most of us are aware – some of us painfully so – that the Hepatitis C drug development market is red hot. Investors and developers alike need a scorecard to keep track of who is buying who and for what potential blockbuster drug in the race to make it big in treating Hepatitis C.  All of this hullabaloo is for good reason – the CDC estimates there are over 170 million people infected with Hepatitis C worldwide[1], a vast majority of them don’t know that they have it.  That is paradoxically both an enormous and lucrative problem. This means there are a lot of potential patients for pharmaceutical companies to treat with blockbuster anti-HCV drugs.

The names of the compounds in development are like alphabet soup – GS-7977, VX-222, BMS-790052, BI-201335, TMC 435, BL-8020… protease inhibitors, polymerase inhibitors, cyclophilin inhibitors… the list goes on and on. This is a good thing for both drug makers and patients. Drugs to treat Hepatitis C are becoming more potent and more tolerable.  And the race for the next blockbuster drug means there is no shortage of drugs and drug classes to choose from.  Drug developers may even realize the holy grail of Hepatitis C treatment – an all oral, interferon-free regimen consisting of 2-4 pills a day. That’s right, no shots, no interferon. This would potentially make treatment for Hepatitis C infinitely more tolerable for patients.

So the HCV drug development biz is booming… but the hottest drug to beat in Hepatitis C?  Ribavirin.  A cheap, generic anti-viral. It turns out that even with all the advances drug makers are realizing in interferon-free drug combinations, ribavirin is critical to the success in curing patients of Hepatitis C.   The trouble is that no one is really sure how ribavirin works. All we know is that treatment response rates are infinitely higher when it is part of a Hepatitis C antiviral regimen.[2][3][4]

Researchers are busy trying to find out just what makes ribavirin tick, but let’s look at a few of the current theories on how the drug works:

Ribavirin may cause something called ‘error catastrophe’ in the lifecycle of the HCV virus.[5]Ribavirin is a nucleoside analog – this means that ribavirin can fool the virus into thinking that it’s one of the building blocks needed for the virus to replicate. So when the virus tries to replicate itself, it picks ribavirin as a building block instead of the real thing. This mucks up the replication process leading to ‘error catastrophe’ – in other words, the virus is no longer able to make copies of itself.
Inosine monophosphate dehydrogenase (IMPDH). That’s a tongue-twister to be sure, but it’s also a cellular enzyme the human body makes and the HCV virus needs. Ribavirin may inhibit this enzyme, which consequently shuts down the energy supply the Hepatitis C virus requires to survive and replicate.[1]
The Hepatitis C virus is sneaky. It has a peculiar knack for evading the body’s immune system[2], so anything that might disrupt that ability would be very valuable to an anti-HCV regimen. It turns out that ribavirin may have this unique ability by helping the body mount a specific anti-viral response to the Hepatitis C virus, which is essential in fully clearing the virus. [3]
While ribavirin’s exact mechanism of action remains a mystery, there is one thing we do know for certain – we need ribavirin to fight Hepatitis C. Paring ribavirin with the above new antiviral compounds currently in development – called Direct Acting Antivirals  or DAAs -  that target and disrupt numerous points in the lifecycle of the virus, lead to significantly better cure rates then just using the DAAs alone. While interferon may go the way of the buffalo, it appears that the lowly, unsexy ribavirin is here to stay.  This makes ribavirin the REAL drug to beat in the Hepatitis C drug development marketplace.

References

[1] Perz JF, et al. The contribution of hepatits B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide. J Hepatol 2006; 45: 529-38

[2] Vertex Pharmaceuticals, Inc. (2010)  Vertex adds ribavirin in additional treatment arm in ongoing phase II VX-222 & Telaprevir combo trial. [Press Release] Retrieved from http://viralmatters.blogspot.com/2010/11/vertex-adds-ribavirin-in-additional.html

[3] Hezode, Christopher, et al. (2009) Telaprevir and Peginterferon with or without Ribavirin for chronic HCV Infection. Retrieved from http://www.nejm.org/doi/full/10.1056/NEJMoa0807650

[4] Smith, M. (2012). New Combo KOs HCV Without Interferon, Ribavirin  [Online article] Retrieved from: http://www.medpagetoday.com/InfectiousDisease/Hepatitis/30739

[5] Maag D, et al. RNA virus error catastrophe: direct molecular test by using ribavirin. Proc. Natl. Acad. Sck. 2001; 98: 6895-900

Encouraging Phase II Telaprevir HIV/HCV coinfection treatment data presented at CROI...

Posted on March 6 on Vertex Pharmaceuticals.com: Data presented at CROI from the Phase II Telaprevir trial looking at the safety and effectiveness of Telaprevir + P/R in the HIV/HCV co-infected patient (all on Atripla and Reyataz as their antiretroviral regimen).  While this is SVR12 data and not the 'true' SVR of 24 weeks past End of Treatment (EOT), this data looks encouraging with 74% (28/38) patients undetectable at SVR12.  Given the huge potential of drug-drug-interactions with Telaprevir and antiretroviral regimens, it looks as if the Atripla + Reyataz regimen in combination with TVR + P/R is the one to go with - VERY encouraging in that there have been no HIV breakthroughs while on TVR + P/R + Reyataz + Atripla. The coinfected patient is a critical patients - coinfected individuals have have markedly increased disease progression far and above that of the monoinfected patient.  Considering that Boceprevir cannot be used in the HIV/HCV coinfected patient, Vertex has this niche all to itself until the 2nd gen compounds prove themselves.  I'm sure these interim results come to the relief of many providers who treat this patient population. 

Data from Phase 2 Study of an INCIVEK® Combination Regimen Showed 74% of People Co-Infected with Hepatitis C and HIV Had Undetectable Hepatitis C Virus 12 Weeks After Treatment Ended (SVR12)

- INCIVEK was well tolerated with commonly used Atripla- and Reyataz-based HIV treatment regimens, and no patients experienced HIV breakthrough -

- Enrollment is ongoing in Phase 3 study evaluating 24- and 48-week treatment durations in people who are co-infected -

SEATTLE--(BUSINESS WIRE)-- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced interim results from an ongoing Phase 2 study designed to evaluate the safety and tolerability of INCIVEK® (telaprevir) tablets in combination with pegylated-interferon and ribavirin in people who are co-infected with genotype 1 hepatitis C virus and human immunodeficiency virus (HIV). Data showed 74 percent (28/38) of patients who were treated with INCIVEK (in-SEE-veck) combination therapy had undetectable hepatitis C virus (HCV RNA) 12 weeks after the end of all study treatment (SVR12) compared to 45 percent (10/22) who were treated with pegylated-interferon and ribavirin alone. INCIVEK was well tolerated with commonly used Atripla®- and Reyataz®-based HIV treatment regimens. Changes in CD4 counts were similar between the treatment groups and no HIV viral load breakthroughs were observed in either treatment group during the study. The most common adverse events in the INCIVEK arms of the study were fatigue, pruritis (itching), headache, nausea and rash. No cases of severe rash were reported and there were no discontinuations due to rash. Interim results from this study are being presented at the Conference on Retroviruses and Opportunistic Infections (CROI), March 5 to 8, 2012 in Seattle.

"Hepatitis C generally progresses faster, leads to more long-term liver complications and has been harder to cure among people who also have HIV," said Robert Kauffman, M.D., Ph.D., Senior Vice President and Chief Medical Officer at Vertex. "These new INCIVEK data are important as we work toward our goal of helping cure more people with hepatitis C. We're actively enrolling co-infected patients in a Phase 3 study and expect that data from this study will be included in a submission for a supplemental approval of INCIVEK."

The Phase 2 study includes two parts: Part A is evaluating people who are not currently being treated with antiretroviral therapy (ART) for HIV infection and Part B is evaluating those who are taking an Atripla- or Reyataz-based regimen for HIV. This study enrolled patients who were new to hepatitis C treatment (treatment naïve). Patients who were randomized to receive INCIVEK were treated with 12 weeks of INCIVEK, pegylated-interferon and ribavirin, followed by 36 weeks of pegylated-interferon and ribavirin alone. Interim data also showed that 68 percent (26/38) of patients treated with INCIVEK combination therapy in this study had a rapid viral response (RVR, undetectable hepatitis C virus at week 4 of treatment) compared to none (0/22) of the patients who received pegylated-interferon and ribavirin alone.

"There is a great need for treatments that are well tolerated and offer co-infected patients a better chance at a cure for hepatitis C while maintaining suppression of their HIV," said Douglas Dieterich, M.D., Professor of Medicine in the Division of Liver Diseases, Mount Sinai School of Medicine, New York City. "It's very encouraging that nearly three out of four people had undetectable hepatitis C virus 12 weeks after stopping INCIVEK combination therapy and that their HIV medicines continued to work during treatment."

Interim Study Results

Sixty-two people 18 and older were enrolled in this Phase 2 study and 60 received at least one dose of study drug. This analysis was conducted 12 weeks after patients completed all treatment. The ART regimens evaluated in this study were selected based on current HIV treatment guidelines from the U.S. Department of Health and Human Services, International AIDS Society and drug-drug interaction studies of INCIVEK with commonly used ART medicines.

Interim Intent To Treat Analysis of Study #110

Part A (No ART)

Part B Atripla®-based regimen

Part B Reyataz®-based regimen

Total

INCIVEK- based Arm+

Control Arm++

INCIVEK- based Arm+

Control Arm++

INCIVEK- based Arm+

Control Arm++

INCIVEK- based Arm+

Control Arm++

RVR*

71% (5/7)

0% (0/6)

75% (12/16)

0% (0/8)

60% (9/15)

0% (0/8)

68% (26/38)

0% (0/22)

eRVR**

57% (4/7)

0% (0/6)

75% (12/16)

0% (0/8)

47% (7/15)

0% (0/8)

61% (23/38)

0% (0/22)

SVR12

71% (5/7)

33% (2/6)

69% (11/16)

50% (4/8)

80% (12/15)

50% (4/8)

74% (28/38)

45% (10/22)

Atripla-based regimen (efavirenz, tenofovir disoproxil fumarate and emtricitabine): INCIVEK was dosed at 1,125 mg, every 8 hours (q8h).

Reyataz-based regimen (ritonavir-boosted atazanavir, tenofovir disoproxil fumarate and emtricitabine or lamivudine): INCIVEK was dosed at 750 mg, every 8 hours (q8h).

*RVR: Rapid Viral Response; undetectable HCV RNA at week 4.

**eRVR: extended Rapid Viral Response; undetectable HCV RNA at weeks 4 and 12.

+12 weeks of INCIVEK, Pegasys® (PEG, pegylated-interferon alfa-2a) and Copegus® (RBV, ribavirin) followed by 36 weeks of only PEG and RBV.

++48 weeks of PEG and RBV only for hepatitis C treatment.

             
Atripla-based regimen (efavirenz, tenofovir disoproxil fumarate and emtricitabine): INCIVEK was dosed at 1,125 mg, every 8 hours (q8h).

Reyataz-based regimen (ritonavir-boosted atazanavir, tenofovir disoproxil fumarate and emtricitabine or lamivudine): INCIVEK was dosed at 750 mg, every 8 hours (q8h).

*RVR: Rapid Viral Response; undetectable HCV RNA at week 4.
**eRVR: extended Rapid Viral Response; undetectable HCV RNA at weeks 4 and 12.

+12 weeks of INCIVEK, Pegasys® (PEG, pegylated-interferon alfa-2a) and Copegus® (RBV, ribavirin) followed by 36 weeks of only PEG and RBV.
++48 weeks of PEG and RBV only for hepatitis C treatment.

The majority of adverse events in this study were mild or moderate. Adverse events that occurred more frequently in the INCIVEK arms compared to placebo (≥10 percent difference) were pruritis (itching), headache, nausea, rash, fever, and depression. Three patients, all in Arm B, discontinued all study treatment due to adverse events (one each due to gall stones, hemolytic anemia and nausea/vomiting).

About this Phase 2 Study

Vertex and its collaborator Janssen conducted extensive drug-drug interaction studies with INCIVEK and commonly used HIV medicines prior to initiating a development program in people co-infected with hepatitis C (HCV) and HIV. This Phase 2 study is a two-part (A and B), randomized, double-blind, placebo-controlled, parallel group, multi-center study in people chronically infected with both HCV and HIV who were new to HCV treatment. The primary endpoint of the study is to evaluate the safety and tolerability of INCIVEK combination therapy in people co-infected with HCV and HIV. A secondary endpoint is to evaluate rates of sustained viral response (SVR) 12 and 24 weeks after the end of treatment. The study is being conducted by Vertex in collaboration with Janssen.

Phase 3 Study Actively Enrolling

Enrollment is ongoing in a Phase 3 study evaluating 24- and 48-week response-guided regimens of INCIVEK combination therapy in people co-infected with HCV and HIV. Patients who are either new to treatment for HCV, or who had relapsed after at least one prior course of therapy with pegylated-interferon and ribavirin alone, will receive 24 or 48 weeks of INCIVEK combination treatment, based on their antiviral response. Patients who had not responded to a prior course of treatment (partial responders and nulls) will receive 48 weeks of INCIVEK combination treatment. A similar study is also being initiated by Janssen in its territories.

Data from In Vitro Evaluation of INCIVEK and HIV Protease Inhibitors

Also being presented at CROI this week are data from an in vitro evaluation of the anti-HIV activity of four HIV protease inhibitors (amprenavir, darunavir, lopinavir and atazanavir) in combination with INCIVEK. In the study, no antagonistic effects on the antiviral activity were observed when INCIVEK was used in combination with amprenavir, darunavir, and lopinavir, and slight antagonistic effects were observed on the antiviral activity of atazanavir.

About INCIVEK

INCIVEK ® (telaprevir) tablets is an oral medicine that acts directly on the hepatitis C virus protease, an enzyme essential for viral replication. INCIVEK is the most prescribed direct-acting antiviral for the treatment of adults with genotype 1 chronic hepatitis C and has been used to treat more than 30,000 people in the United States.

INCIVEK was approved by the U.S. Food and Drug Administration (FDA) in May 2011 and by Health Canada in August 2011 for use in combination with pegylated-interferon and ribavirin for people with genotype 1 chronic hepatitis C with compensated liver disease (some level of damage to the liver but the liver still functions), including cirrhosis (scarring of the liver). INCIVEK is approved for people who are new to treatment, and for people who were treated previously with interferon-based treatment but who did not achieve a sustained viral response, or viral cure (relapsers, partial responders and null responders).

Vertex developed telaprevir in collaboration with Janssen and Mitsubishi Tanabe Pharma. Vertex has rights to commercialize telaprevir in North America where it is being marketed under the brand name INCIVEK (in-SEE-veck). Janssen has rights to commercialize telaprevir in Europe, South America, Australia, the Middle East and certain other countries. In September 2011, telaprevir was approved in the European Union and Switzerland. Telaprevir is known as INCIVO® in Europe. Mitsubishi Tanabe Pharma has rights to commercialize telaprevir in Japan and certain Far East countries. In September 2011, telaprevir was approved in Japan and is known as Telavic®.

INCIVEK® is a registered trademark of Vertex Pharmaceuticals Incorporated.

PEGASYS® and COPEGUS® are registered trademarks of Hoffmann-La Roche.

Reyataz® is a registered trademark of Bristol-Myers Squibb.

Atripla® is a registered trademark of Bristol-Myers Squibb and Gilead Sciences, LLC.

About Hepatitis C

Hepatitis C is a serious liver disease caused by the hepatitis C virus, which is spread through direct contact with the blood of infected people and ultimately affects the liver.1 Chronic hepatitis C can lead to serious and life-threatening liver problems, including liver damage, cirrhosis, liver failure or liver cancer.1 Though many people with hepatitis C may not experience symptoms, others may have symptoms such as fatigue, fever, jaundice and abdominal pain.1

Unlike HIV and hepatitis B virus, chronic hepatitis C can be cured.2 However, approximately 60 percent of people do not achieve SVR,3,4,5 or viral cure,6 after treatment with 48 weeks of pegylated-interferon and ribavirin alone. If treatment is not successful and a person does not achieve a viral cure, they remain at an increased risk for progressive liver disease.7,8

More than 170 million people worldwide are chronically infected with hepatitis C.6 In the United States, nearly 4 million people have chronic hepatitis C and 75 percent of them are unaware of their infection.9 Hepatitis C is four times more prevalent in the United States compared to HIV.9 The majority of people with hepatitis C in the United States were born between 1946 and 1964, accounting for two of every three people with chronic hepatitis C.10 Hepatitis C is the leading cause of liver transplantations in the United States and is reported to contribute to 4,600 to 12,000 deaths annually.11,12 By 2029, total annual medical costs in the United States for people with hepatitis C are expected to more than double, from $30 billion in 2009 to approximately $85 billion.9

About Hepatitis C and HIV Co-Infection

There are 1 million people living with HIV in the United States, and an estimated 300,000 people living with HIV/AIDS in the United States are also infected with hepatitis C. 13 There have been dramatic improvements in the treatment of HIV and the prognosis for people living with HIV. However, liver disease progresses more rapidly in people co-infected with hepatitis C and HIV, with an increased rate of progression to cirrhosis, decompensated liver disease, hepatocellular carcinoma and death. 14, 15, 16, 17 The hepatitis C cure rate with a 48-week treatment of pegylated-interferon and ribavirin, the current standard of care for people with co-infection, is approximately 29 percent.18

About Vertex

Vertex creates new possibilities in medicine. Our team discovers, develops and commercializes innovative therapies so people with serious diseases can lead better lives.

Vertex scientists and our collaborators are working on new medicines to cure or significantly advance the treatment of hepatitis C, cystic fibrosis, rheumatoid arthritis, epilepsy and other life-threatening diseases.

Founded more than 20 years ago in Cambridge, MA, we now have ongoing worldwide research programs and sites in the U.S., U.K. and Canada. Today, Vertex has more than 2,000 employees around the world, and Science magazine named Vertex number one on its 2011 list of Top Employers in the life sciences.

Vertex's press releases are available at www.vrtx.com.

Special Note Regarding Forward-Looking Statements

This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, including Dr. Kauffman's statements in the second paragraph of this press release and statements regarding ongoing and planned Phase 3 studies of INCIVEK combination therapy in people co-infected with HCV and HIV. While the company believes the forward-looking statements contained in this press release are accurate, there are a number of factors that could cause actual events or results to differ materially from those indicated by such forward-looking statements. Those risks and uncertainties include, among other things, that the outcomes from future clinical trials of INCIVEK combination therapy in co-infected patients may not be favorable and the other risks listed under Risk Factors in Vertex's annual report and quarterly reports filed with the Securities and Exchange Commission and available through Vertex's website at www.vrtx.com. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.

IMPORTANT SAFETY INFORMATION

Indication

INCIVEK® (telaprevir) is a prescription medicine used with the medicines peginterferon alfa and ribavirin to treat chronic (lasting a long time) hepatitis C genotype 1 infection in adults with stable liver problems, who have not been treated before or who have failed previous treatment. It is not known if INCIVEK is safe and effective in children under 18 years of age.

Important Safety Information

INCIVEK should always be taken in combination with peginterferon alfa and ribavirin. Ribavirin may cause birth defects or death of an unborn baby. Therefore, a patient should not take INCIVEK combination treatment if she is pregnant or may become pregnant, or if he is a man with a sexual partner who is pregnant. Patients must use two forms of effective birth control during treatment and for the 6 months after treatment with these medicines. Hormonal forms of birth control, including birth control pills, vaginal rings, implants or injections, may not work during treatment with INCIVEK.

INCIVEK and other medicines can affect each other and can also cause side effects that can be serious or life threatening. There are certain medicines patients cannot take with INCIVEK combination treatment. Patients should tell their healthcare providers about all the medicines they take, including prescription and non-prescription medicines, vitamins and herbal supplements.

INCIVEK can cause serious side effects including skin reactions, rash and anemia that can be severe. The most common side effects of INCIVEK include itching, nausea, diarrhea, vomiting, anal or rectal problems, taste changes and tiredness. There are other possible side effects of INCIVEK, and side effects associated with peginterferon alfa and ribavirin also apply to INCIVEK combination treatment. Patients should tell their healthcare providers about any side effect that bothers them or doesn't go away.

Please see full Prescribing Information for INCIVEK including the Medication Guide, available at www.INCIVEK.com.

(VRTX-GEN)

References:

1 Centers for Disease Control and Prevention. Hepatitis C Fact Sheet: CDC Viral Hepatitis. Available at: http://www.cdc.gov/hepatitis/HCV/PDFs/HepCGeneralFactSheet.pdf. Accessed February 22, 2012.

2 Pearlman BL and Traub N. Sustained Virologic Response to Antiviral Therapy for Chronic Hepatitis C Virus Infection: A Cure and So Much More. Clin Infect Dis. 2011 Apr;52(7):889-900.

3 Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001;358:958-965.

4 Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002;347:975-982.

5 McHutchison JG, Lawitz EJ, Shiffman ML, et al; IDEAL Study Team. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J Med. 2009;361:580-593.

6 Ghany MG, Strader DB, Thomas DL, Seeff, LB. Diagnosis, management and treatment of hepatitis C; An update. Hepatology. 2009;49 (4):1-40.

7 Morgan TR, Ghany MG, Kim HY, Snow KK, Lindsay K, Lok AS. Outcome of sustained virological responders and non-responders in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) trial. Hepatology. 2008;50(Suppl 4):357A (Abstract 115).

8 Veldt BJ, Heathcote J, Wedmeyer H. Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis. Annals of Internal Medicine. 2007; 147: 677-684.

9 Institute of Medicine of the National Academies. Hepatitis and liver cancer: a national strategy for prevention and control of hepatitis B and C. Colvin HM and Mitchell AE, ed. Available at: http://www.iom.edu/Reports/2010/Hepatitis-and-Liver-Cancer-A-National-Strategy-for-Prevention-and-Control-of-Hepatitis-B-and-C.aspx. Updated January 11, 2010. Accessed February 22, 2012.

10 Pyenson B, Fitch K, Iwasaki K. Consequences of hepatitis C virus (HCV): Costs of a baby boomer epidemic of liver disease. Available at: http://www.natap.org/2009/HCV/051809_01.htm. Updated May 2009. Accessed February 22, 2012. This report was commissioned by Vertex Pharmaceuticals, Inc.

11 Volk MI, Tocco R, Saini S, Lok, ASF. Public health impact of antiviral therapy for hepatitis C in the United States. Hepatology. 2009;50(6):1750-1755.

12 Davis GL, Alter MJ, El-Serag H, Poynard T, Jennings LW. Aging of hepatitis C virus (HCV)-infected persons in the United States: A multiple cohort model of HCV prevalence and disease progression. Gastroenterology. 2010;138:513-521.

13 HIV Advocate. HIV/HCV Coinfection. Available at: http://www.hcvadvocate.org/hepatitis/factsheets_pdf/HIV_HCV20coinfecton_10.pdf. Accessed February 28, 2012.

14 Martin-Carbonero L, Benhamou Y, Puoti M, Berenguer J, Mallolas J, Quereda C, et al. Incidence and predictors of severe liver fibrosis in human immunodeficiency virus-infected patients with chronic hepatitis C: a European collaborative study. CID 2004;38:128-33.

15 Martinez-Sierra C, Arizcorreta A, Diaz F, Roldan R, Martin-Herrera M, Perez- Guzman E, et al. Progression of chronic hepatitis C to liver fibrosis and cirrhosis in patients coinfected with hepatitis C virus and human immunodeficiency virus. CID 2003;36:491-8.

16 Matthews GV, Dore GJ. HIV and hepatitis C coinfection. JGH. 2008; 23: 1000-1008.

17 Bruno R, Sacchi P, Puoti M, Soriano V, Filice G. HCV chronic hepatitis in patients with HIV: clinical management issues Am J Gastroenterol 2001; 97:1598—1606.

18 Levin, J. Pegasys/RBV in APRICOT Study- Adherence Improves SVR 300% in genotype 1. Available at: http://www.natap.org/2005/ICAAC/icaac_31.htm Accessed February 28, 2012.



Vertex Pharmaceuticals Incorporated

Media:

Dawn Kalmar
Erin Emlock
Zach Barber
617-444-6992
mediainfo@vrtx.com

or

Investors:
Michael Partridge, 617-444-6108
or
Lora Pike, 617-444-6755

Source: Vertex Pharmaceuticals Incorporated

News Provided by Acquire Media

HCAB Position Statement: Hepatitis C Drug Development and Drug-Drug Interaction Studies...

This HCAB (Hepatitis C Community Advisory Board) position statement was published on 2/28/12 regarding Hepatitis C drug development and drug-drug interaction (DDI) studies. In short, the HCAB would like drug developers to be more proactive in doing DDI studies before the drugs come to market. They admonish Merck specifically for not doing DDI studies with commonly available antiretrovirals and their HCV antiviral drug, boceprevir. Further, they applaud the efforts of Vertex and J&J for doing full due diligence in DDI studies prior to the launch of Telaprevir. 

HCAB Position Statement: Hepatitis C Drug Development and Drug-Drug Interaction Studies

February 17, 2012 -- The Hepatitis C Community Advisory Board (HCAB) recognizes the value of more effective and less toxic treatment for hepatitis C virus (HCV). We believe that sponsors can conduct key drug-drug interaction (DDI) studies with direct-acting antivirals (DAAs) and other candidates in development and medications commonly used by people with hepatitis C and those coinfected with HIV/HCV prior to their approval, without delaying development of these important therapies.

DAAs may share metabolic pathways with drugs that are commonly used by populations with a high prevalence of hepatitis C, such as hormonal contraceptives, methadone, buprenorphine, lipid-lowering agents, immunosuppressive drugs, herbal remedies, and commonly prescribed psychiatric medications.

In recognition of the suboptimal efficacy and tolerability of [pegylated interferon] and ribavirin, rapid trajectory of liver disease progression, and increasing mortality from HCV-related complications among HIV/HCV coinfected patients, regulators in the US and the EU encourage sponsors to conduct trials in HIV/HCV coinfected patients prior to approval for HCV monoinfection. Sponsors have already opened, or plan to launch these trials.

The recent discovery of drug-drug interactions between boceprevir and boosted HIV protease inhibitors underscores the importance of DDI studies with DAAs. Although we commend the sponsor, Merck, for opening one of the first coinfection trials with a DAA, we were outraged that Merck chose not to conduct DDIs with commonly used antiretroviral agents prior to launching the trial, and prior to gaining approval for boceprevir. Vertex and Tibotec were able to bring telaprevir [Incivek] to market with a much fuller portfolio of DDI data, although both drugs were developed within the same timeframe.

HCAB asks FDA [the US Food and Drug Administration], EMA [European Medicines Agency] and pharmaceutical companies to work together to minimize potential harm to hepatitis C monoinfected and HIV/HCV coinfected patients from uncharacterized drug-drug interactions. Furthermore, we call upon sponsors to perform DDI studies (as indicated by metabolic profile of their drug or drugs) with DHHS [US Department of Health and Human Services], EACS [European AIDS Clinical Society] and WHO [World Health Organization]-recommended antiretroviral agents for first-line, and treatment-experienced HIV/HCV coinfected people prior to approval, and strongly encourage studies of hormonal contraceptives, methadone, buprenorphine, lipid-lowering agents, immunosuppressive drugs, herbal remedies, and commonly prescribed psychiatric medications.

2/28/12

Source

Hepatitis C Community Advisory Board. HCAB Position Statement: Hepatitis C Drug Development and Drug-Drug Interaction Studies. February 16, 2012.

Hepatitis C: Drugmakers jockey to create cocktail...

Bloomberg News article published in the San Francisco Chronicle on 2/15/2012 on the recent M&As and speculation on the M&As to come. Very nice overview if you're new to the HCV drug development space and have a hankerin' to learn who the big players are.


Hepatitis C: Drugmakers jockey to create cocktail


Bloomberg News
Wednesday, February 15, 2012

A developing medical theory that hepatitis C can be overcome with the same type of drug cocktails that tamed HIV is shaking up the pharmaceutical industry.

Companies are trying to anticipate which medicines might work best together and planning their acquisition strategies accordingly. Because only a few hepatitis C drugs are approved, and others in testing may not pan out, "we don't know what the winning formula will be," said Ben Weintraub, an analyst at Wolters Kluwer InThought. To raise the odds, "companies are doing M&A (mergers and aquisitions) and starting new trials on almost a daily basis."

With more than two dozen drugs in development, doctors predict a new age of therapy for a blood-borne virus carried by 170 million people that now has few treatment options. The promise of a potential $20 billion market has already spurred three deals in the past year - the latest being Bristol-Myers Squibb's $2.5 billion purchase this month of Inhibitex.
Next in line may be Idenix Pharmaceuticals and Achillion Pharmaceuticals, said Raghuram Selvaraju, an analyst with Morgan Joseph TriArtisan.

"I don't think either of these companies will remain independent very long," Selvaraju said. "I think we'll see both of them out of there by the end of the year."

Increased urgency
Achillion is testing a so-called protease inhibitor, while Idenix is developing a nucleotide polymerase inhibitor. The two medicines, which work differently to block the virus' ability to replicate in the body, are in the second of three stages of testing normally required for U.S. approval.

By combining several classes of these new hepatitis C drugs, doctors may be able to limit the virus' ability to infect, mimicking the strategy that a decade earlier helped turn HIV from a killer disease to a controlled one, said Charles Chiu, an infectious disease doctor at UCSF.

With the success of treatments that "work on the virus itself, there's an increased urgency now to explore drugs in many different stages of the viral life cycle," Chui said.

Until last year's introduction of Victrelis from Merck and Incivek by Vertex Pharmaceuticals - two protease inhibitors - the standard treatment combined the antiviral drug ribavirin with interferon, an immune-boosting protein sold by Merck as PegIntron and by Roche as Pegasys.

That treatment relied on interferon shots given weekly for a year, and it cured only about half of patients with the most common U.S. strain, called genotype 1. The drugs also caused side effects that include fatigue and flu-like symptoms.

Across different types
The new protease inhibitors stop an enzyme that splits proteins and allows them to replicate. While they've been shown to cure more patients in less time than previous therapies, with fewer side effects, they still need to be combined with interferon shots.

Scientists see promise in the other class being developed, the nucleotide polymerase inhibitors, which bind to a different part of the virus than the protease inhibitors. These drugs are pan-genotypic - meaning they are effective across the different types of hepatitis C. They could become the backbone for an interferon-free combination.

Mixing the classes together may be even more effective in beating the disease, which is blamed for more than 350,000 deaths a year worldwide.

"We waited 15 years for protease inhibitors, and a year later we could have a new class of drugs, nucleotides, that surpass them," said Steve Worland, former CEO of Anadys Pharmaceuticals, an experimental hepatitis C drugmaker acquired by Roche in November for about $230 million. "That kind of dramatic change I have never seen before."

Drugmakers want to own a piece of the eventual cocktail that will work best among patients worldwide. They've been working in the lab to create their own drugs, as well as scouting other companies with an eye toward buying promising candidates.

Takeover targets
Foster City's Gilead Sciences paid $10.8 billion for Pharmasset last month to use its experimental nucleotide drug, PSI-7977, as a cornerstone to a new hepatitis C combination - one that it expects other drugmakers will want to use - opening the door to added licensing revenue.

Selvaraju said: "7977 is going to be the driver of an all-oral regimen, and all of these other drugs are going to be layered on top of it."

Rivals have the same idea as they hunt for potential targets. That's why Achillion and Idenix are being closely watched as potential takeover targets, Selvaraju said. Abbott Laboratories and Roche are potential bidders, he said. Merck, Bristol-Myers and Johnson & Johnson are also in pursuit of the new regimens.

The potential market size for these therapies is at least $20 billion, according to Michael Kishbauch, CEO of Achillion.

Competition grows
Gilead increased its offer to acquire Pharmasset four times last year to $137 per share from $100 per share, after a clinical trial showed PSI-7977 cured all patients in a study.

"The opportunity to be able to cure people with three months of therapy is one of the most amazing breakthroughs we can bring to health care - and there's a lot of competition," Gilead CEO John Martin said last month.

Idenix is in talks to find a partner to create a combination hepatitis C treatment, said Ron Renaud, the company's CEO. While declining to comment on whether the company may be acquired, he said interest in hepatitis C drugs picked up last year during a liver disease conference.

"There is a tremendous market opportunity here that people want to take advantage of, and there's an intense race that's under way to get to that point," Renaud said.

http://sfgate.com/cgi-bin/article.cgi?f=/c/a/2012/02/15/BUDC1N7L0U.DTL
his article appeared on page D - 1 of the San Francisco Chronicle

Merck posts 'Dear Doctor' letter regarding use of Victrelis with boosted HIV protease inhibitors...

Thank you NATAP.org. DHCP letter that came out today (Feb 6th, 2012) regarding drug-drug interactions with Boceprevir and ritonovir-boosted PIs. In short. "Merck does not recommend the coadministration of VICTRELIS and ritonavir-boosted HIV protease inhibitors." 



S. Sethu K. Reddy, MD Merck & Co., Inc.


Vice President PO Box 250

US Medical Affairs West Point, PA 19486-0250


February 6, 2012

IMPORTANT DRUG WARNING

SUBJECT: Results of Pharmacokinetic Study in Healthy Volunteers Given VICTRELIS™

(boceprevir) and Ritonavir-Boosted HIV Protease Inhibitors May Indicate Clinically Significant Drug

Interactions for Patients Coinfected with Chronic Hepatitis C and HIV


Dear Health Care Professional,

The purpose of this communication is to inform you of recent pharmacokinetic study results evaluating drug

interactions between VICTRELIS, an oral chronic hepatitis C virus (HCV) NS3/4A protease inhibitor, and

ritonavir-boosted human immunodeficiency virus (HIV) protease inhibitors in healthy volunteers (n=39).

VICTRELIS is indicated for the treatment of chronic hepatitis C virus (HCV) genotype 1 (G1) infection, in

combination with peginterferon alfa and ribavirin (PR), in adult patients (18 years and older) with

compensated liver disease, including cirrhosis, who are treatment-naïve or who have failed previous

interferon and ribavirin therapy. In the pharmacokinetic study, concomitant administration of VICTRELIS

with Norvir® (ritonavir) in combination with Reyataz® (atazanavir) or Prezista® (darunavir), or with Kaletra®

(lopinavir/ritonavir) resulted in reduced exposures of the HIV medicines and VICTRELIS. Specifically,

VICTRELIS reduced mean trough concentrations of ritonavir-boosted atazanavir, lopinavir, and darunavir

by 49%, 43%, and 59%, respectively. Mean reductions of 34% to 44% and 25% to 36% were observed in

AUC and Cmax of atazanavir, lopinavir, and darunavir. Coadministration of ritonavir-boosted atazanavir with

VICTRELIS did not alter the exposure of VICTRELIS, but coadministration of VICTRELIS with

lopinavir/ritonavir or ritonavir-boosted darunavir decreased the exposure of VICTRELIS by 45% and 32%,

respectively.

These drug interactions may be clinically significant for patients infected with both chronic HCV and HIV by

potentially reducing the effectiveness of these medicines when coadministered. VICTRELIS is not indicated

for use in patients who are infected with both HIV-1 and chronic HCV. The safety and efficacy of

VICTRELIS™ (boceprevir) has not been established in this coinfected population. Merck does not

recommend the coadministration of VICTRELIS and ritonavir-boosted HIV protease inhibitors.

Health care providers who might have initiated VICTRELIS in combination with PR in HIV-HCV coinfected

patients on fully suppressive antiretroviral therapy containing a ritonavir-boosted protease inhibitor should

discuss these findings with those patients, and closely monitor those patients for HCV treatment response

and for potential HCV and HIV virologic rebound.

Patients should be advised to contact their health care provider before stopping any of their

medications.

Merck is sharing these pharmacokinetic data with regulatory authorities in the countries where VICTRELIS

is approved. Merck will be submitting requests to regulators to update the product labeling with these data.

These data have been submitted for scientific presentation at an upcoming medical forum.

For more information, please consult the enclosed Prescribing Information for VICTRELIS. The Prescribing

Information can also be found at http://www.merck.com/product/usa/pi_circulars/v/victrelis/victrelis_pi.pdf.

Should you have any questions, require further information on product safety, or wish to report an adverse

event with VICTRELIS, please contact Merck at 1-877-888-4231. Alternatively, an adverse event can be

reported directly to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Sincerely,

S. Sethu K. Reddy, MD

Enclosure: Prescribing Information for VICTRELIS

- 3 -

Indications and Usage for VICTRELISTM (boceprevir)

VICTRELIS was approved by the US Food and Drug Administration (FDA) on May 13, 2011 for the

treatment of chronic hepatitis C virus (HCV) genotype 1 (G1) infection, in combination with peginterferon

alfa and ribavirin (PR), in adult patients (18 years and older) with compensated liver disease, including

cirrhosis, who are previously untreated or who have failed previous interferon and ribavirin therapy.

The following points should be considered when initiating VICTRELIS for treatment of chronic HCV

infection:

• VICTRELIS must not be used as monotherapy and should only be used in combination with PR.

• VICTRELIS efficacy has not been studied in patients who have previously failed therapy with a treatment

regimen that includes VICTRELIS or other HCV NS3/4A protease inhibitors.

• VICTRELIS in combination with PR has not been studied in patients documented to be historical null

responders (<2-log10 HCV-RNA decline by Treatment Week 12) during prior therapy with PR. The clinical

studies included subjects who were poorly interferon responsive. Subjects with <0.5-log10 HCV-RNA

decline in viral load at Treatment Week 4 with PR alone are predicted to have a null response (<2-log10

viral load decline at Treatment Week 12) to PR therapy.

• Poorly interferon responsive patients who were treated with VICTRELIS in combination with PR have a

lower likelihood of achieving a sustained virologic response (SVR), and a higher rate of detection of

resistance-associated substitutions upon treatment failure, compared to patients with a greater response

to PR.

Selected Safety Information for VICTRELIS

All contraindications to PR also apply since VICTRELIS must be administered with PR.

Because ribavirin may cause birth defects and fetal death, VICTRELIS in combination with PR is

contraindicated in pregnant women and in men whose female partners are pregnant. Avoid pregnancy in

female patients and female partners of male patients. Patients must have a negative pregnancy test prior to

therapy; have monthly pregnancy tests; and use 2 or more forms of effective contraception, including

intrauterine devices and barrier methods, during treatment and for at least 6 months after treatment has

concluded. Systemic hormonal contraceptives may not be as effective in women while taking VICTRELIS

and concomitant ribavirin.

VICTRELIS is contraindicated in coadministration with drugs that are highly dependent on CYP3A4/5 for

clearance, and for which elevated plasma concentrations are associated with serious and/or life-threatening

events. VICTRELIS is also contraindicated in coadministration with potent CYP3A4/5 inducers, where

significantly reduced VICTRELIS plasma concentrations may be associated with reduced efficacy.

Drugs that are contraindicated with VICTRELIS include: alfuzosin, carbamazepine, phenobarbital,

phenytoin, rifampin, dihydroergotamine, ergonovine, ergotamine, methylergonovine, cisapride, St. John’s

Wort (hypericum perforatum), lovastatin, simvastatin, drosperinone, Revatio® (sildenafil) or Adcirca®

(tadalafil) (when used for the treatment of pulmonary arterial hypertension), pimozide, triazolam, and orally

administered midazolam.

- 4 -

Anemia and/or Neutropenia – The addition of VICTRELIS™ (boceprevir) to PR is associated with an

additional decrease in hemoglobin concentrations compared with PR alone and/or may result in worsening

of neutropenia associated with PR therapy alone. Dose reduction or discontinuation of peginterferon alfa

and/or ribavirin may be required. Dose reduction of VICTRELIS is not recommended. VICTRELIS must not

be administered in the absence of PR.

Complete blood count (with white blood cell differential counts) must be conducted in all patients prior to

initiating combination therapy with VICTRELIS. Complete blood counts should be obtained at Treatment

Weeks 4, 8, and 12, and should be monitored closely at other time points, as clinically appropriate.

The most commonly reported adverse reactions (>35%) in clinical trials in adult patients receiving the

combination of VICTRELIS with PR were: fatigue, anemia, nausea, headache, and dysgeusia. Of these

commonly reported adverse reactions, fatigue, anemia, nausea, and dysgeusia occurred at rates ≥5%

above the rates for PR alone in either clinical study. The incidence of these adverse reactions in previously

untreated subjects that were treated with combination therapy with VICTRELIS compared with PR alone

were: fatigue (58% vs 59%), anemia (50% vs 30%), nausea (46% vs 42%), and dysgeusia (35% vs 16%),

respectively. The incidence of these adverse reactions in previous treatment failure patients that were

treated with combination therapy with VICTRELIS compared with PR alone were: fatigue (55% vs 50%),

anemia (45% vs 20%), nausea (43% vs 38%), and dysgeusia (44% vs 11%), respectively.

VICTRELIS is a strong inhibitor of CYP3A4/5 and is partly metabolized by CYP3A4/5. The potential for

drug-drug interactions must be considered prior to and during therapy.