Zacks Investment Research on HCV market....

Zacks analysis of the current HCV market and speculation of what's to come. Interesting read especially if you're new to the HCV drug development space.

Spotlight On Hepatitis-C Market
By Zacks Investment Research on December 6, 2011

Is the hepatitis-C market the next Mecca for the pharma/biotech sector? It seems so if we go by the flurry of activity and heightened interest in this market in the past few quarters. The hepatitis-C virus (HCV) market seems to have caught the eye of several pharma/biotech companies – as evident by the deals being signed for the development of drugs for the treatment of HCV.

We are talking about the recent announcements made by big players like Johnson & Johnson (NYSE:JNJ), Bristol-Myers Squibb (NYSE:BMY) and Gilead Sciences, Inc. (NASDAQ:GILD). All three companies have made it clear they want a piece of the HCV market pie.

Johnson & Johnson’s Tibotec Pharmaceuticals and Bristol-Myers Squibb recently announced that they have decided to join forces for the development of Bristol-Myers’ daclatasvir (BMS-790052) in combination with Tibotec’s TMC435, for the treatment of chronic HCV. What the partners are aiming to do is create an oral once-daily interferon-free cocktail treatment for HCV patients.

Bristol-Myers and Johnson & Johnson’s announcement comes on the heels of Gilead’s announcement regarding its intention to buy Pharmasset, Inc. (NASDAQ:VRUS), a company focused on developing HCV treatments. We think the main attraction for Gilead in this $11 billion deal is Pharmasset’s HCV pipeline. Lead candidate PSI-7977 is currently in two phase III studies, with a third phase III study scheduled to commence in the first half of 2012. Successful development could lead to US approval in 2014 thereby making Gilead a front-runner in the oral once-daily interferon-free cocktail treatment HCV market.

We note that both TMC435 and daclatasvir are being evaluated separately in combination with Pharmasset’s PSI-7977.

The Allure of the HCV Market

HCV is a hot development area which has come into the limelight with the launch of two new treatments – Vertex Pharmaceuticals’ (NASDAQ:VRTX) Incivek and Merck’s (NYSE:MRK) Victrelis. Both drugs gained approval in the US earlier this year. Incivek, which was launched in May 2011, posted a whopping $419.6 million in sales in the first full quarter of its launch.

So, with two new recently launched products in the market, why is the HCV market considered so attractive? Firstly, it is estimated that about 170 million people suffer from HCV infection across the world. However, the treated population is much lower. In major markets like the US, EU, Japan, Australia, Turkey, Canada, etc. only 200,000 HCV patients out of a total of more than 12 million are estimated to receive treatment each year. This means a huge number of HCV patients go untreated, leaving the field open for new treatments.

Secondly, the current standard of care comes with several side effects which make it difficult for patients to remain on treatment. A 48-week course of both peg-interferon (peg-INF – weekly injections) and ribavirin (RBV – oral drug), are the standard treatment for genotype 1 HCV infection. However, this treatment regimen is associated with significant side-effects like fatigue, flu-like symptoms, rash, depression and anemia.

With a large number of HCV patients failing to achieve a sustained viral response (SVR) on the current standard of care, there are several patients who would be open to treatment with new and potentially more effective therapies.

These factors have made the HCV market an attractive commercial opportunity for pharma and biotech companies. Victrelis and Incivek are examples of the changing treatment regimen in the HCV market. Both are protease inhibitors which when added to the standard of care reduce the treatment period and also improve the treatment outcome. However, both need to be administered with peg-IFN and RBV – this leaves the path open for the introduction of treatments with fewer side effects.

Cocktail Therapy – The Next Big Thing in HCV

Companies like Johnson & Johnson and Gilead are trying to develop the next crop of drugs, which are expected to change the treatment paradigm for HCV patients by providing them with all-oral treatment regimens. The aim is to develop a treatment which does not require the administration of interferon, thereby doing away with a whole range of side effects. The treatment duration will also be shorter.

Treatments being developed include HCV polymerase inhibitors and HCV NS5A inhibitors. The future HCV market will most likely consist of cocktail treatment regimens developed by combining different oral treatments.

Vertex Pharma has also recognized the need to continually evolve the HCV treatment pattern and is developing an all-oral combination of VX-222 (a polymerase inhibitor) and Incivek without peg-IFN.

Who Will Win the Rat Race?

With several companies pursuing cocktail therapies for HCV, it will be interesting to see which of these companies will be the first to hit the market with a new treatment option. Currently, it looks like Gilead might be the front-runner assuming the Pharmasset acquisition goes through.

The Motley Fool's Sean Williams on Inhibitex....

Inhibitex Shares Popped: What You Need to Know

By Sean Williams
December 1, 2011

Although we don't believe in timing the market or panicking over market movements, we do like to keep an eye on big changes -- just in case they're material to our investing thesis.

What: Shares of Inhibitex, one of many biotechnology companies involved in hepatitis C research, jumped as much as 13% earlier in the trading session before giving up almost all of its gains.

So what: Ever since Gilead Sciences agreed to purchase Pharmasset last week at a hefty premium, the sector has been abuzz with more buyout speculation. Optimists got more fuel for the fire earlier in the week when Inhibitex reported positive phase 2 results for INX-189, its experimental hepatitis C drug. Today's move appears to be a carryover effect of the bullishness from previous days.

Now what: To say that I'm not a fan of Inhibitex at its current valuation north of $1.1 billion might be an understatement. The company is going to face an onslaught of competition from Gilead and Pharmasset, but also from hep C drugs that are already approved by the FDA for sale, including Merck's Victrelis and Vertex Pharmaceuticals' Incivek. Then there's the fact that Inihibtex has already sold 1.9 million shares of stock into this unbelievable rally. With its leading drug candidate only in phase 2 clinical trials, there are plenty of moves left to be played in this chess game before I'd declare Inhibitex a winner. I'm so confident Inhibitex is overvalued at these levels I'm willing to bet my CAPS points on it!

The Motley Fool comments on the next generation of Hepatitis C drug therapy...

The Motley Fool's take on the future of HCV drug development, buyouts and partnerships. Once the fodder for small biotechs, Big Pharma has their eye on the marketplace. That means plenty of action in the coming months in the quest to usurp Telaprevir's crown.

Gunning for the Leaders

By Brian Orelli
October 31, 2011

Merck's (NYSE: MRK ) Victrelis and Vertex Pharmaceuticals' (Nasdaq: VRTX ) Incivek have been on the market for only five months, and the threats to unseat them keep coming.

Data on some of the next-generation hepatitis C drugs will be presented at the end of this week, when the annual meeting of the American Association for the Study of Liver Diseases kicks off. Add in top-line data that's been released recently and expected results in the next few months, and the hepatitis C space is looks like it'll get really crowded, really quickly.

The biotech front-runner
Pharmasset (Nasdaq: VRUS ) has grabbed most of the spotlight. The company has a drug, RG7128, partnered with Roche, but most of the focus has been on PSI-7977 that it owns in its entirety. The company will present data at the meeting including results using PSI-7977 as a monotherapy. Reducing or eliminating peginterferon, which must be used with Incivek and Victrelis, is a goal of every next-generation hepatitis C regimen because of nasty side effects with peginterferon.

Achillion Pharmaceuticals (Nasdaq: ACHN ) will make multiple presentations at the meeting, with its phase 2 compound, ACH-1625, being the most interesting. Idenix Pharmaceuticals has a pair of presentations at the meeting.

No shortage of pharma competition
Unfortunately for the smaller biotechs, Big Brother is interested in the space as well.

Earlier this month, Abbott Labs (NYSE: ABT ) said it has a drug combination that might be able to deliver cure rates as high as 90% without peginterferon. Don't write off the others just yet, though. It was a fairly small trial, and the data from more patients might not be as impressive.

Bristol-Myers Squibb (NYSE: BMY ) recently presented data for one of its compounds, BMS-790052. In a phase 2 trial, 83% of patients taking the two highest doses of BMS-790052 had undetectable viral levels 24 weeks after treatment, compared with just 25% who took just peginterferon alfa and ribavirin. But the results with BMS-790052 required adding it to peginterferon and ribavirin.

The upside to pharma's interest
Fortunately for biotechs, combination treatments are likely to be key to ridding patients of the virus. Resistance issues are common, but they can be avoided by combining medications that attack the virus in different ways.

No doubt Roche's acquisition of Anadys earlier this month was driven by its desire to get a hold of Anadys' hepatitis C treatment, setrobuvir. While we might see more acquisitions in the works, partnerships -- especially non-exclusive ones -- could be the best solution for both sides. Pharmasset has used the double-dipping strategy making pacts with both Johnson & Johnson (NYSE: JNJ ) and Bristol-Myers to combine their hepatitis C treatments with PSI-7977.

The problem with non-exclusive pacts is that they may not provide biotechs with much cash to fund their own development. On the other hand, if a biotech doesn't make too many of them, it could lead to a takeout offer.

Which combo is the combo?
It's hard to know which combination will eventually win out. When you start adding multiple drugs to each other, there's bound to be side-effect issues that aren't a problem when they're used individually. Hepatitis C is a little less life-threatening than HIV, so the FDA will demand a cleaner side-effect profile than they have for cocktails that treat HIV.

And while finding the most potent combination is important, it's useful only if they complement each other's resistance issues; knocking the virus down to undetectable levels in 100% of the patients isn't particularly useful if the virus just rebounds once it mutates in a way to avoid the drugs' inhibitory properties.

Rather than trying to guess which company will eventually profit, buying a basket of hepatitis C drugmakers might be the best move. If a combo treatment is going to eventually work, why not a combination of investments?

The EU approves Boceprevir for treatment of chronic HCV....

The European Commission approved Boceprevir for treatment of chronic HCV. It will be interesting to see how socialized medicine within the members of the EU provides access to the DAAs for HCV, given their dizzying costs coupled with the economic crisis of some of the more notable member nations.

WHITEHOUSE STATION, N.J., Jul 18, 2011 (BUSINESS WIRE) -- Merck /quotes/zigman/574389/quotes/nls/mrk MRK -1.22% , known as MSD outside the United States and Canada, today announced that the European Commission (EC) has approved VICTRELIS(TM)(boceprevir) for the treatment of chronic hepatitis C (CHC) genotype 1 infection, in combination with peginterferon alfa and ribavirin, in adult patients with compensated liver disease who are previously untreated or who have failed previous therapy. Chronic hepatitis C virus (HCV) is a potentially serious viral infection of the liver that affects an estimated 4 million people in Europe.

The European Commission's Decision grants a single marketing authorisation that is valid in the 27 countries that are members of the European Union (EU), as well as unified labeling applicable to the European Economic Area members, Iceland, Liechtenstein and Norway.

"The EU approval of VICTRELIS for chronic hepatitis C genotype 1 is very exciting, because we now have a new option for patients with the hardest to treat form of the disease. With VICTRELIS, patients who have failed previous therapy or are new to treatment can significantly improve their chances of clearing the virus from their bodies compared to current standard therapy," said Rafael Esteban, M.D., head of the internal medicine and liver unit of the Hospital Universitario Val d'Hebron, Barcelona, Spain. "For some patients new to treatment, VICTRELIS also may allow for a shorter total duration of therapy."

VICTRELIS is the first in a new class of medicines known as HCV protease inhibitors. It is a Direct Acting Antiviral (DAA) agent designed to interfere with the ability of the hepatitis C virus to replicate by inhibiting a key viral enzyme (NS3/4A serine protease). Current standard therapy for HCV works to strengthen the body's natural immune response to the virus, but a majority of patients with chronic hepatitis C genotype 1 are not able to achieve a sustained virologic response (SVR).(1)

"VICTRELIS is the first major advancement for the treatment of chronic hepatitis C approved in the EU in a decade, and represents an important step forward for people living with this serious disease and the physicians who treat them," said Bruno Strigini, president, Europe/Canada, Merck. "Recognizing the high unmet need in this area, Merck will work closely with local authorities across the EU to make VICTRELIS available to patients as quickly as possible."

The marketing authorization for VICTRELIS in combination with current standard therapy is based on the efficacy and safety results from two large pivotal Phase III clinical studies conducted at European and North American sites that evaluated approximately 1,500 adult patients with chronic HCV genotype 1 infection who were previously untreated or who had failed prior therapy. Both studies included two treatment arms with VICTRELIS: a response-guided therapy (RGT) arm, in which patients with undetectable virus (HCV-RNA) at treatment week 8 were eligible for a shorter duration of therapy, as well as a 48-week treatment arm. All patients receiving VICTRELIS in these studies were first treated with peginterferon alfa-2b and ribavirin (P/R) in a 4-week lead-in phase, followed by the addition of VICTRELIS after week 4. The studies also included a control arm in which patients received 48 weeks of treatment with P/R alone. Final results of the HCV SPRINT-2 (treatment-naive) study and the HCV RESPOND-2 (treatment-failure) study were published in the New England Journal of Medicine on March 31, 2011.

VICTRELIS in the United States

VICTRELIS was approved by the U.S. Food and Drug Administration on May 13 and is available to all U.S. pharmacies nationwide, including specialty pharmacies.

VICTRELIS is indicated in the U.S. for the treatment of chronic hepatitis C genotype 1 infection, in combination with peginterferon alfa and ribavirin, in adult patients (18 years of age 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 hepatitis C infection:

-- VICTRELIS must not be used as monotherapy and should only be used in combination with peginterferon alfa and ribavirin.

-- 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 peginterferon alfa and ribavirin has not been studied in patients documented to be historical null responders (less than a 2 log HCV-RNA decline by treatment week 12) during prior therapy with peginterferon alfa and ribavirin. The clinical studies included patients who were poorly interferon responsive. Patients with less than 0.5 log HCV-RNA decline in viral load at treatment week 4 with peginterferon alfa plus ribavirin alone are predicted to have a null response (less than a 2 log HCV-RNA decline by treatment week 12) to peginterferon alfa and ribavirin therapy.

-- Poorly interferon responsive patients who were treated with VICTRELIS in combination with peginterferon alfa and ribavirin 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 peginterferon alfa and ribavirin.

Important U.S. safety information about VICTRELIS

All contraindications to peginterferon alfa and ribavirin also apply since VICTRELIS must be administered with peginterferon alfa and ribavirin. Because ribavirin may cause birth defects and fetal death, VICTRELIS in combination with peginterferon alfa and ribavirin 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 two 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.

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 also is contraindicated in coadministration with potent CYP3A4/5 inducers where significantly reduced boceprevir 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(R) (sildenafil) or Adcirca(R) (tadalafil) (when used for the treatment of pulmonary arterial hypertension), pimozide, triazolam, and midazolam (orally administered).

Anemia has been reported with peginterferon alfa and ribavirin therapy. The addition of VICTRELIS to peginterferon alfa and ribavirin is associated with an additional decrease in hemoglobin concentrations. The addition of VICTRELIS may result in a worsening of neutropenia associated with peginterferon alfa and ribavirin alone. Complete blood counts should be obtained pretreatment, and at treatment weeks 4, 8 and 12, and should be monitored closely at other time points, as clinically appropriate. If a patient has a serious adverse reaction potentially related to peginterferon alfa and ribavirin therapy, the peginterferon alfa and/or ribavirin dose should be reduced or discontinued. VICTRELIS must not be administered in the absence of peginterferon alfa and ribavirin.

The most commonly reported adverse reactions (greater than 35 percent) in clinical trials in adult patients receiving the combination of VICTRELIS with peginterferon alfa-2b and ribavirin were fatigue, anemia, nausea, headache and dysgeusia. Of these commonly reported adverse reactions, fatigue, anemia, nausea, and dysgeusia occurred at rates greater than or equal to 5 percent above the rates for peginterferon alfa and ribavirin alone in either clinical study. The incidence of these adverse reactions in previously untreated patients who received VICTRELIS combination therapy compared with peginterferon and ribavirin alone were: fatigue (58 vs. 59 percent), anemia (50 vs. 30 percent), nausea (46 vs. 42 percent), dysgeusia (35 vs. 16 percent), respectively. The incidence of these adverse reactions in previously treated patients who received VICTRELIS combination therapy compared with peginterferon and ribavirin alone were: fatigue (55 vs. 50 percent), anemia (45 vs. 20 percent), nausea (43 vs. 38 percent), dysgeusia (44 vs. 11 percent), 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.

Please see U.S. prescribing information at: http://www.merck.com/product/usa/pi_circulars/v/victrelis/victrelis_pi.pdf .

Merck's global commitment to advancing hepatitis therapy

Merck is committed to building on its strong legacy in the field of viral hepatitis by continuing to discover, develop and deliver vaccines and medicines to help prevent and treat viral hepatitis. In hepatitis C, company researchers developed the first approved therapy for chronic HCV in 1991 and the first combination therapy in 1998. In addition to ongoing studies with VICTRELIS, extensive research efforts are underway to develop additional innovative oral therapies for viral hepatitis treatment.

About Merck

Today's Merck is a global healthcare leader working to help the world be well. Merck is known as MSD outside the United States and Canada. Through our prescription medicines, vaccines, biologic therapies, and consumer care and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to healthcare through far-reaching policies, programs and partnerships. For more information, visit www.merck.com .

Forward-Looking Statement

This news release includes "forward-looking statements" within the meaning of the safe harbor provisions of the United States Private Securities Litigation Reform Act of 1995. Such statements may include, but are not limited to, statements about the benefits of the merger between Merck and Schering-Plough, including future financial and operating results, the combined company's plans, objectives, expectations and intentions and other statements that are not historical facts. Such statements are based upon the current beliefs and expectations of Merck's management and are subject to significant risks and uncertainties. Actual results may differ from those set forth in the forward-looking statements.

The following factors, among others, could cause actual results to differ from those set forth in the forward-looking statements: the possibility that the expected synergies from the merger of Merck and Schering-Plough will not be realized, or will not be realized within the expected time period; the impact of pharmaceutical industry regulation and health care legislation; the risk that the businesses will not be integrated successfully; disruption from the merger making it more difficult to maintain business and operational relationships; Merck's ability to accurately predict future market conditions; dependence on the effectiveness of Merck's patents and other protections for innovative products; the risk of new and changing regulation and health policies in the United States and internationally and the exposure to litigation and/or regulatory actions.

Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in Merck's 2010 Annual Report on Form 10-K and the company's other filings with the Securities and Exchange Commission (SEC) available at the SEC's Internet site ( www.sec.gov ).

Please see Prescribing Information for VICTRELIS at http://www.merck.com/product/usa/pi_circulars/v/victrelis/victrelis_pi.pdf and Medication Guide for VICTRELIS at http://www.merck.com/product/usa/pi_circulars/v/victrelis/victrelis_mg.pdf .

(1)SVR, the protocol specified primary efficacy endpoint of the pivotal studies, is defined as achievement of undetectable HCV-RNA at 24 weeks after the end of treatment in all randomized patients treated with any study medication. Per protocol, if a patient did not have a 24-week post-treatment assessment, the patient's 12-week post-treatment assessment was utilized.

VICTRELIS(TM) is a trademark of Schering Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, N.J., USA.

Revatio(R) and Adcirca(R) are trademarks of their respective owners and are not trademarks of Merck & Co., Inc., Whitehouse Station, N.J., USA.

SOURCE: Merck

Merck
Media:
Pamela Eisele, 908-423-5042
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The Motley Fool on the J&J/Pharmasset partnership....

J&J's Been Busy

http://www.fool.com/investing/general/2011/07/07/jjs-been-busy.aspx

Brian Orelli
July 7, 2011

When it comes to virus inhibition, Johnson & Johnson (NYSE: JNJ ) has been getting around. Last week, the health-care giant signed a partnership with Gilead Sciences (Nasdaq: GILD ) to combine their HIV drugs. And yesterday, Johnson & Johnson announced it was hooking up with a different partner, Pharmasset (Nasdaq: VRUS ) , to create a hepatitis C drug combo.

The duo plan to run a phase 2 trial combining the companies' experimental drug candidates: PSI-7977 from Pharmasset and TMC435 from Johnson & Johnson. They'll start in patients that have already failed a round of treatment, but if the drugs show success, the companies will surely move into treatment-naive patients.

The press release didn't mention any financial details. Maybe they're waiting to see if they're compatible before putting a name on their relationship.

Like the HIV market, the future of hepatitis C treatment is a cocktail that's hopefully capable of curing everyone. Incivek and Victrelis from Vertex Pharmaceuticals (Nasdaq: VRTX ) and Merck (NYSE: MRK ) , respectively, are combined with older medications to help boost the cure rate from around half of the treated patients to as much as 79%.

But that still leaves room for improvement. And the older medications -- Merck's PegIntron and Roche's Pegasys -- have to be injected and have unpleasant side effects. Going to an all-oral regimen is the ultimate goal.

Hepatitis C drugmakers with limited compounds are scrambling to partner up to avoid being left behind. Pharmasset has a similar deal combining PSI-7977 with a drug from Bristol-Myers Squibb (NYSE: BMY ) . Merck and Roche have also hooked up to test their drug candidates.

Gilead has six hepatitis C compounds in clinical trials that it can mix or match to find the right combo on its own, which might explain why Johnson & Johnson didn't hit up its HIV partner for another go around in hepatitis C.

NY York Times "Prescriptions" blog on "The Hidden Price of Drugs".

An editorial from Andrew Pollack of NY Times' "Prescriptions" blog. He points out that is drug companies aren't always up front when it comes to the cost of new drugs or price increases for older ones. He includes Merck and Vertex's new drugs for Hepatitis C as examples. Not a very exciting or particularly incisive read, but he does make a good point not always obvious to people outside the business of drug development.


May 31, 2011, 4:09 pm

The Hidden Price of Drugs
By ANDREW POLLACK

Pharmaceutical companies are happy to tout the benefits of their newest drugs. But sometimes they seem far less willing to let the public know the price of the product.

The latest example occurred on Tuesday morning when Optimer Pharmaceuticals announced that its new drug to treat diarrhea caused by the bacterium Clostridium difficile would cost $2,800, about twice as much as the existing approved drug.

On Friday, Optimer announced in a press release that the Food and Drug Administration had approved its drug, called Dificid. But the company kept the price out of the press release, saying it would not reveal it until its conference call with securities analysts Tuesday morning.

Whatever the reason for the tactic, it had the result of keeping discussions about what many would consider eye-popping prices out of initial articles about the drug’s approval.

Vertex Pharmaceuticals did this as well after the recent approval of its hepatitis C drug, Incivek. The press release contained a lot of information about how generous the company was going to be in helping customers with their insurance co-payments. But it did not include how much the drug would actually cost — $49,000.

In that case, however, the call with analysts in which the price was unveiled came only about two hours after the approval was announced.

It could be pointed out that analyst calls are also a more supportive environment for a company. Analysts often applaud “premium’’ pricing because it means higher sales for a drug, whereas patients and insurers would have the opposite view.

Merck did put the $1,100-a-week price of its new hepatitis C drug, Victrelis, in its press release. But the price was mentioned in a single short sentence at the very bottom of a press release that was more than 250 lines long.

Dr. Jeffrey H. Albrecht, a gastroenterologist at Hennepin County Medical Center and a professor of medicine at the University of Minnesota, said he was frustrated trying to find documented information, outside of news reports, on the price of the new hepatitis C drugs.

“When you take a step back,’’ he said in an e-mail, “it is really remarkable that patients and physicians often don’t know how much treatments or tests cost.’’

Actually, Merck, Vertex and Optimer did more to make their prices public than some companies, which never reveal their prices. And some companies say they do not want to reveal the price until they actually begin marketing the drug, which in some cases can be weeks or even months after the regulatory approval.

A spokeswoman for Vertex said that price was complicated since patients did not usually pay the listed wholesale price. An analyst call, therefore, was a better way to reveal the information.

“We wanted to get the information out quickly but also avoid confusion about an important and complicated topic,’’ she said.

A spokesman for Optimer said it was not customary to put prices in press releases, and that telling the price to analysts allowed the company put the information in context.

On the call Tuesday morning, Optimer’s chief executive, Pedro Lichtinger argued that the $2,800 price for a 10-day course of treatment with Dificid was in line with prices for some other new antibiotics.

He said Dificid would be cost-effective because it might cut down on hospital stays and other costs associated with treating C. difficile. In clinical trials, Dificid was superior to the only other approved drug, Vancocin, in providing a “sustained clinical response,’’ he said.

Vancocin, an oral form of the antibiotic vancomycin sold by ViroPharma, costs $1,000 to $1,500 for a 10- to 14-day course of treatment at the lowest dose, Mr. Lichtinger said. But some patients get higher doses or longer treatments, multiplying the cost.

ViroPharma has been steadily raising the price of Vancocin and has taken legal action to try to delay approval of generic versions of the drug. Still, many hospitals get around the price of Vancocin by using the intravenous form of vancomycin, which is generic, in a manner that lets patients take it orally.

Former archenemies Merck and Roche form a Hepatitis C alliance....

Even the most casual of observers of Pharma industries machinations would have to agree that it's been a rough five days for Vertex. Their main competitor, Merck, gets first mover advantage, a best-case label, AND effectively buys loyalty in a marketing alliance with it's former archenemy, Roche. Roche gets peace of mind that Merck won't drop it's drawers on Peg-Intron and Boceprevir bundling to gain formulary access, leaving it's cash cow Pegasys out of harms way and potential for even greater sales. Vertex has to partner with Pegasys regardless of the alliance because Pegasys was the only interferon used in Telaprevir's Phase III pivotal trials. I'm not right about a whole bunch of things, more than I'd like to admit, but I've never been wrong regarding Merck as a marketing juggernaut. Genius move that may give Boceprevir greater strength against Telaprevir's sure-to-come broadsides on efficacy and dosing schedule.

Merck Girds For Hep C Battle With Roche Deal
Adam Feuerstein
05/17/11 - 12:40 PM EDT

WHITEHOUSE STATION, N.J. (TheStreet) -- Merck(MRK) gained an unlikely ally in the hyper-competitive battle to market a new crop of hepatitis C drugs.

Roche said Tuesday that it will promote in the U.S. Merck's newly approved drug Victrelis in combination with its own hepatitis C drug Pegasys under a broader marketing and research alliance signed between the two drug giants.

What makes this partnership unusual is that Roche and Merck have been long-time hepatitis C treatment competitors. The new arrangement aligns the interests of two pharmaceutical marketing powerhouses, which for Merck is especially helpful as it strikes out to compete against Vertex Pharmaceuticals(VRTX) and its new hepatitis C drug.

Roche's Pegasys, or weekly interferon injection, has about 80% market share to Merck's own long-acting interferon injection, Peg-Intron, which has about 20% market share.

Under this new agreement, Roche will be promoting the use of Merck's Victrelis in combination with Pegasys as a new, triple-combination therapy against hepatitis C. Victrelis was approved in the U.S. last Friday, making it the first in a new class of direct-acting antiviral agents against hepatitis C.

Vertex is expecting to receive similar U.S. approval on or before May 23 for its drug, Incivek. The launch of two new and similar hepatitis C drugs promises to ignite one of the fiercest drug marketing battles in years.

The Merck-Roche deal is not exclusive, which means that Roche, at some point, could agree to a similar deal with Vertex to promote Incivek. Vertex, however, may not necessarily need Roche's direct help because Incivek is already closely tied to Pegasys. Incivek's pivotal clinical trials used Roche's Pegasys as the long-acting interferon backbone, whereas Merck tested Victrelis in combination with its own Peg-Intron.

Still, bringing Roche on board to promote Victrelis is a coup for Merck because it adds a new and experienced sales force that will be able to educate doctors about how to best use Victrelis. One of the issues weighing on Merck is the complex and often confusing dosing schedules required with Victrelis as compared to a much simpler dosing schedule for Vertex's Incivek.

Victrelis and Incivek have never been compared in a head-to-head study but the Vertex drug is also widely viewed as more effective -- able to cure upwards of 80% of newly treated patients compared to an approximate 60% cure rate for Merck's drug.

Merck and Roche did not disclose financial terms of the deal but a Merck spokesman said that Merck retains 100% of the Victrelis economics even with the Roche marketing deal in place. Presumably, that means Roche will not receive a royalty on Victrelis sales but will gain as more doctors choose to use its Pegasys with either Victrelis or Incivek. Roche may have also been worried that Merck was planning to tempt doctors with a discounted bundle of Peg-Intron with Victrelis that could have hurt Pegasys market share.

Under terms of the agreement, Merck and Roche will also cooperate on new studies that will seek to combine Victrelis with Roche's experimental hepatitis C drugs. This new research alliance can include experimental drugs that Roche licensed from other companies, including one from Pharmasset(VRUS), according to a Roche spokeswoman.

--Written by Adam Feuerstein in Boston.

TheStreet's Adam Feuerstein runs the numbers on the approval of Boceprevir....

It's always interesting to see what TheStreet.com's Adam Feuerstein has to say about anything related to the Direct Acting Antivirals, coming from a business perspective. I think he's dead on here. The only thing I'd add in regards to both Telaprevir and Boceprevir is that Boceprevir's studies of drug interactions isn't very robust and needs to be better characterized. Telaprevir's is sure to be VERY detailed, Telaprevir being a pretty potent inhibitor of CYP 450 and Vertex doing the due diligence to do drug interaction studies with common medications.

Merck Strikes First in Hep C Drug Battle
Adam Feuerstein
05/16/11 - 08:33 AM EDT

WHITEHOUSE STATION, NJ (TheStreet) -- The U.S. approval Friday of Merck's(MRK) hepatitis C drug Victrelis was expected. More surprising was the drug's "best case" label that will help Merck better compete in the new hepatitis C treatment market.

The U.S. Food and Drug Administration approved Victrelis with a broad label that basically gives Merck what it wanted, which is to leave decisions about how best to use the hepatitis C drug in the hands of physicians. The downside for Merck to this broad discretion on Victrelis' label is that doctors may have too many complicated dosing options.

Vertex Pharmaceuticals(VRTX) could exploit any confusion caused by Victrelis' label. Vertex's hepatitis C drug Incivek is expected to receive U.S. approval later this month with a more straightforward and easy-to-understand dosing schedule. Vertex's Incivek is also more potent, curing a greater percentage of hepatitis C patients compared to Merck's Victrelis, at least according to the respective clinical trials run by both companies.

The stakes are high in the new hepatitis C treatment market. Approximately 3.2 million Americans are infected with the viral disease that attacks and progressively destroys the liver. Most people infected with hepatitis C don't know they have the disease and aren't diagnosed until liver damage occurs, which can take years.

The old gold-standard treatment regimen for hepatitis C -- 48 weekly injection of interferon and daily doses of oral ribavirin -- cured about 40% of patients. Adding Victrelis to that regimen will shorten treatment duration for some and improve cure rates to more than 60%. Likewise, Vertex's Incivek will also shorten treatment and boost cure rates to as high as 80%.

The looming marketing battle between Merck and Vertex is worth billions of dollars in new hepatitis C drug sales.

For now, at least, Merck has the market to itself -- the prize for being first to approval. Victrelis will cost $1,100 per week, which means patients and insurers will pay between $26,000 and $48,000 for Victrelis, depending on the length of treatment. This price doesn't include the cost of interferon and ribavirin, which adds another $25,000 to $35,000, again, depending on duration of treatment.

Figuring out how much Victrelis will cost is complicated because the drug's label includes four different treatment suggestions ranging from 26 weeks to 44 weeks. Doctors must first start patients on a four-week lead in of interferon and ribavirin before adding Victrelis. The course of Victrelis should be 28, 36, or 44 weeks long depending on how patients respond at various time points.

The Victrelis label is complex, but Merck is happy because the FDA could have been more restrictive. Merck didn't study Victrelis in so-called "null responders" -- the hardest-to-treat hepatitis C patients -- yet FDA didn't exclude them from the Victrelis label. The FDA also went relatively easy on safety warnings about Victrelis causing anemia -- the drug's most worrisome side effect.

Investors have fairly low expectations for Victrelis so it remains to be seen whether the better-than-expected label helps Merck compete better against Vertex. At this point, Vertex's Incivek is expected to garner about 70% of the new hepatitis C treatment market, according to many analyst forecasts.

Vertex is expecting U.S. approval of Incivek on May 23 with a label that will likely include just two relatively straightforward treatment options of 24 or 48 weeks. Both regimens include the same 12-week course of Incivek, the only difference is the length of interferon and ribavirin use.

Vertex studied Incivek in the hardest-to-treat null responder patients and cured about 30% of them compared to 3% cured with interferon and ribavirin alone. For the best-responding patients, cure rates approach 80% with a relatively short six months of treatment. While Victrelis causes anemia, Vertex's Incivek causes rash, sometimes severe.

Once Incivek is approved, the hepatitis C marketing battle between Merck and Vertex can begin.

Boceprevir gets FDA approval, first to market in the battle against HCV...

A historic moment for both Merck and HCV genotype 1 infected patients as the FDA approves Boceprevir for the treatment of chronic genotype 1 hepatitis C. Boceprevir is the first of the Direct Acting Antivirals (DAAs) specifically targeting HCV to make it to market and represents the largest shift in how this disease is treated since ribavirin was found to have synergistic activity with interferon in the '90's. The first generation of DAAs are far from perfect, but no doubt they will add tremendous leverage in curing patients of the HCV virus. With great achievements comes great responsibility however – physicians and the patients they treat have to be thoroughly fluent in managing AE’s and compliance.

FDA Approves Merck's VICTRELIS™ (boceprevir), First-in-Class Oral Hepatitis C Virus (HCV) Protease Inhibitor


WHITEHOUSE STATION, N.J.--(BUSINESS WIRE)-- Merck (NYSE:MRK) (known as MSD outside the United States and Canada) announced today that the U.S. Food and Drug Administration (FDA) has approved VICTRELIS" (boceprevir), the company's innovative new medicine for the treatment of chronic hepatitis C (CHC). VICTRELIS is approved for the treatment of CHC genotype 1 infection, in combination with peginterferon alfa and ribavirin, in adult patients (18 years of age 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 hepatitis C infection:

VICTRELIS must not be used as monotherapy and should only be used in combination with peginterferon alfa and ribavirin.
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 peginterferon alfa and ribavirin has not been studied in patients documented to be historical null responders (less than a 2 log HCV-RNA decline by treatment week 12) during prior therapy with peginterferon alfa and ribavirin. The clinical studies included patients who were poorly interferon responsive. Patients with less than 0.5 log HCV-RNA decline in viral load at treatment week 4 with peginterferon alfa plus ribavirin alone are predicted to have a null response (less than a 2 log HCV-RNA decline by treatment week 12) to peginterferon alfa and ribavirin therapy.
Poorly interferon responsive patients who were treated with VICTRELIS in combination with peginterferon alfa and ribavirin have a lower likelihood of achieving a sustained virologic response (SVR)1, and a higher rate of detection of resistance-associated substitutions upon treatment failure, compared to patients with a greater response to peginterferon alfa and ribavirin.
VICTRELIS is the first in a new class of medicines approved to treat chronic hepatitis C

VICTRELIS is the first in a new class of medicines known as hepatitis C virus (HCV) protease inhibitors approved for use in combination with peginterferon alfa and ribavirin, which is the current standard therapy, for the treatment of chronic hepatitis C.

This is an exciting day for physicians and patients because VICTRELIS is the first major advancement for the treatment of chronic hepatitis C approved in a decade, said Bruce Bacon, M.D., professor of internal medicine, Saint Louis University School of Medicine, and a clinical investigator for VICTRELIS. Compared to current standard therapy, VICTRELIS can significantly increase a patient s chance of achieving undetectable levels of the virus, thereby obtaining an SVR. For many patients, VICTRELIS may allow for a shorter total duration of treatment.

Merck is deeply committed to innovation in bringing forward new medicines that significantly address unmet medical needs, and VICTRELIS is a shining example of our commitment being realized," said Kenneth C. Frazier, president and chief executive officer, Merck. "We look forward to building on our legacy in the fight against infectious diseases, and to being a part of this exciting new era in the treatment of chronic hepatitis C."

Merck will begin shipping VICTRELIS to pharmacies within a week so that patients will have access to this new medication as soon as possible. In addition, the company is expanding its support of public awareness and education programs for chronic hepatitis C. Resources include coupons to help eligible patients with their medication cost, reimbursement support to help patients understand their insurance coverage for VICTRELIS, and 24/7 nurse phone support.

Separately, Merck will also add VICTRELIS to its patient assistance program through which eligible patients may be able to receive product free of charge.

Current standard therapy for HCV works to strengthen the body s natural immune response to the virus, but only about 40 percent of patients with chronic HCV genotype 1 infection are able to achieve SVR. VICTRELIS is a Direct Acting Antiviral (DAA) agent that interferes with the ability of the hepatitis C virus to replicate by inhibiting a key viral enzyme (NS3/4A serine protease).

The FDA approval of VICTRELIS is based on the efficacy and safety results from two large Phase III clinical studies that evaluated approximately 1,500 adult patients with chronic HCV genotype 1 infection. Both studies included two treatment arms with VICTRELIS: a response-guided therapy (RGT) arm, in which patients with undetectable virus (HCV-RNA) at treatment week 8 were eligible for a shorter duration of therapy, as well as a 48-week treatment arm. All patients receiving VICTRELIS in these studies were first treated with peginterferon alfa-2b and ribavirin (P/R) in a 4-week lead-in phase, followed by the addition of VICTRELIS after week 4. The studies also included a control arm in which patients received 48 weeks of treatment with P/R alone. Historical null responders were not enrolled.

Adding VICTRELIS to P/R achieved a significant increase in SVR rates compared to P/R alone

Primary results from the two pivotal studies:

Treatment-failure patients: the addition of VICTRELIS to P/R resulted in nearly a three-fold increase in SVR rates to 59 percent (96/162) for the RGT arm and 66 percent (106/161) for the 48-week treatment arm, compared to 23 percent (18/80) for control. Relapse rates were 14 percent (16/111) for the RGT arm and 12 percent (14/121) for the 48-week treatment arm, compared to 28 percent (7/25) for control.

Treatment-naïve patients: the addition of VICTRELIS to P/R resulted in a significant increase (1.7 fold) in SVR rates to 63 percent (232/368) for the RGT arm and 66 percent (242/366) for the 48-week treatment arm, compared to 38 percent (138/363) for control. Relapse rates were 9 percent (24/257) for the RGT arm and 9 percent (24/265) for the 48-week treatment arm, compared to 22 percent (39/176) for control.

In a separate, pre-specified cohort of 159 Black treatment-naïve patients, the addition of VICTRELIS to P/R resulted in a significant increase in SVR to 42 percent (22/52) for the RGT arm and 53 percent (29/55) for the 48-week treatment arm, compared to 23 percent (12/52) for control. Relapse rates were 12 percent (3/25) for the RGT arm and 17 percent (6/35) for the 48-week treatment arm, compared to 14 percent (2/14) for control.

Many patients receiving VICTRELIS in combination therapy were early responders at treatment week 8

Secondary analyses from the two pivotal studies were as follows:

Treatment-failure patients: 46 percent (74/162) of patients in the RGT arm and 52 percent (84/161) of patients in the 48-week treatment arm receiving VICTRELIS had undetectable virus (HCV-RNA) at treatment week 8 and were considered early responders, compared to 9 percent (7/80) for control. The SVR rate for these early responders was 88 percent (65/74) in the RGT arm and 88 percent (74/84) in the 48-week treatment arm, compared to 100 percent (7/7) for control. Early responders in the RGT arm were eligible to stop all treatment at week 36.

Treatment-naïve patients: 57 percent (208/368) of patients in the RGT arm and 56 percent (204/366) of patients in the 48-week treatment arm receiving VICTRELIS had undetectable virus (HCV-RNA) at treatment week 8 and were considered early responders, compared to 17 percent (60/363) for control. The SVR rate for these early responders was 88 percent (184/208) in the RGT arm and 90 percent (184/204) in the 48-week treatment arm, compared to 85 percent (51/60) for control. Early responders in the RGT arm were eligible to stop all treatment at week 28.

SVR achieved with VICTRELIS in combination therapy in late responders

Treatment-failure patients: Patients who had detectable virus (HCV-RNA) at treatment week 8, but undetectable virus (HCV-RNA) at treatment week 12, and completed at least 36 weeks of treatment, were considered late responders. The SVR rate for these late responders was 79 percent (27/34) in the RGT arm and 72 percent (29/40) in the 48-week treatment arm. Late responders in the RGT arm stopped VICTRELIS at week 36 and continued P/R alone for an additional 12 weeks (48 weeks total).

Treatment-naïve patients: Patients who had detectable virus (HCV-RNA) at treatment week 8, but undetectable virus (HCV-RNA) at treatment week 24, and completed at least 28 weeks of treatment, were considered late responders. The SVR rate for these late responders was 66 percent (45/68) in the RGT arm and 75 percent (55/73) in the 48-week treatment arm. Late responders in the RGT arm stopped VICTRELIS at week 28 and continued P/R alone for an additional 20 weeks (48 weeks total).

VICTRELIS in combination therapy increased SVR rates in specific patient populations

The addition of VICTRELIS to P/R in treatment-failure patients with less than a 1 log decline in virus (HCV-RNA) during the 4-week lead-in resulted in an increase in SVR rates to 33 percent (15/46) for the RGT arm and 34 percent (15/44) for the 48-week treatment arm, compared to 0 percent (0/12) for control.

In treatment-failure patients with cirrhosis at baseline, 77 percent (17/22) achieved SVR with the addition of 44 weeks of VICTRELIS to P/R, compared to 35 percent (6/17) for those who received RGT.
In treatment-naïve patients with cirrhosis at baseline, 42 percent (10/24) achieved SVR with the addition of 44 weeks of VICTRELIS to P/R, compared to 31 percent (5/16) for those who received RGT.

Safety and tolerability profile of VICTRELIS in 2,095 patients in Phase II and III studies

Serious adverse events were reported in 11 percent of patients receiving VICTRELIS in combination with P/R, compared to 8 percent of patients receiving P/R alone.

During the entire course of treatment, the proportion of patients who discontinued treatment due to adverse reactions was 13 percent for patients receiving VICTRELIS in combination with P/R, compared to 12 percent for patients receiving P/R alone. Events resulting in discontinuation were similar to those seen in previous studies with P/R alone.

Adverse reactions that led to dose modifications of any drug (primarily P/R) occurred in 39 percent of patients receiving the combination of VICTRELIS with P/R compared to 24 percent of patients receiving P/R alone.
The most common reason for dose reduction was anemia, which occurred more frequently in patients receiving the combination of VICTRELIS with P/R than in patients receiving P/R alone.

The proportion of patients who experienced anemia was higher in patients receiving VICTRELIS in combination with P/R than in those treated with P/R alone. With management of anemia, the average additional decrease of hemoglobin was approximately 1 g/dL. Dose modifications (generally of P/R) due to anemia occurred more often in patients treated with VICTRELIS in combination with P/R (26 percent), compared to those treated with P/R alone (13 percent). Treatment discontinuations due to anemia were similar for patients receiving VICTRELIS in combination with P/R
(1 percent) compared to those treated with P/R alone (1 percent).

Erythropoietin (EPO) with or without ribavirin dose reduction for management of anemia was allowed at the discretion of the investigator per the study protocol.

In pivotal clinical studies, the 4-week lead-in provided important clinical insights

Interferon-responsiveness (equal to or greater than a 1 log decline in virus (HCV-RNA) at treatment week 4) was predictive of SVR. Patients receiving VICTRELIS who demonstrated interferon-responsiveness at treatment week 4 achieved higher SVR rates than those with poor interferon-responsiveness (less than a 1 log decline in virus (HCV-RNA) at treatment week 4). During the four-week lead-in period with P/R in the treatment arms containing VICTRELIS, 2 percent (28/1263) of patients experienced adverse reactions leading to discontinuation of treatment.

Background on the pivotal Phase III studies for VICTRELIS

The HCV RESPOND-2 study (treatment-failure patients) and the HCV SPRINT-2 study (treatment-naïve patients) each evaluated two treatment strategies with VICTRELIS added to P/R to assess the ability of VICTRELIS to improve SVR rates and potentially shorten overall treatment duration, compared to the use of P/R alone for 48 weeks, which is the current standard duration of therapy.

In both studies, all patients receiving VICTRELIS were treated with a 4-week lead-in of peginterferon alfa-2b (1.5 mcg/kg/week) and an investigational dose of ribavirin (600-1,400 mg/day), followed by the addition of VICTRELIS (800 mg three times a day) after week 4.

In each study, patients were randomized to three groups:

Response-guided therapy (RGT), in which patients with undetectable virus (HCV-RNA) at treatment week 8 were considered early responders and were eligible for a shorter duration of therapy. Treatment-naïve patients with undetectable HCV-RNA during weeks 8 through 24 were eligible to stop all treatment at week 28. Treatment-failure patients with undetectable HCV-RNA at treatment weeks 8 and 12 were eligible to stop all treatment at week 36.

48 weeks of treatment, in which patients received a 4-week lead-in with P/R followed by 44 weeks of VICTRELIS in combination with P/R.
Control, in which patients received P/R for 48 weeks.

In the HCV RESPOND-2 study, all patients with detectable virus (HCV-RNA) at treatment week 12 were discontinued from treatment. In the HCV SPRINT-2 study, all patients with detectable virus (HCV-RNA) at treatment week 24 were discontinued from treatment.

The HCV RESPOND-2 study was conducted at U.S. and international sites, and included 403 adult patients who had failed prior treatment, including patients who relapsed or were partial responders to prior treatment with standard therapy. Historical null responders were not enrolled. Patients were randomized in a 1:2:2 ratio and stratified based on response to their previous qualifying regimen (relapsers vs. partial responders) and by HCV genotype (1a or 1b).

The HCV SPRINT-2 study was conducted at U.S. and international sites in 1,097 adult patients who were new to treatment. Patients were randomized in a 1:1:1 ratio within two separate cohorts (938 non-Black patients and 159 Black patients) and were stratified by HCV genotype (1a or 1b) and by HCV-RNA viral load (less than or equal to 400,000 IU/mL vs. greater than 400,000 IU/mL). Black patients with chronic HCV historically have been shown to be harder to treat successfully.

Final results of the HCV RESPOND-2 and HCV SPRINT-2 studies were published in the New England Journal of Medicine on March 31, 2011.

Important safety information about VICTRELIS

All contraindications to peginterferon alfa and ribavirin also apply since VICTRELIS must be administered with peginterferon alfa and ribavirin. Because ribavirin may cause birth defects and fetal death, VICTRELIS in combination with peginterferon alfa and ribavirin 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 two 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 also is contraindicated in coadministration with potent CYP3A4/5 inducers where significantly reduced boceprevir 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 midazolam (orally administered).

Anemia has been reported with peginterferon alfa and ribavirin therapy. The addition of VICTRELIS to peginterferon alfa and ribavirin is associated with an additional decrease in hemoglobin concentrations. The addition of VICTRELIS may result in a worsening of neutropenia associated with peginterferon alfa and ribavirin alone. Complete blood counts should be obtained pretreatment, and at treatment weeks 4, 8 and 12, and should be monitored closely at other time points, as clinically appropriate. If a patient has a serious adverse reaction potentially related to peginterferon alfa and ribavirin therapy, the peginterferon alfa and/or ribavirin dose should be reduced or discontinued. VICTRELIS must not be administered in the absence of peginterferon alfa and ribavirin.

The most commonly reported adverse reactions (greater than 35 percent) in clinical trials in adult patients receiving the combination of VICTRELIS with peginterferon alfa-2b and ribavirin were fatigue, anemia, nausea, headache and dysgeusia. Of these commonly reported adverse reactions, fatigue, anemia, nausea, and dysgeusia occurred at rates greater than or equal to 5 percent above the rates for peginterferon alfa and ribavirin alone in either clinical study. The incidence of these adverse reactions in previously untreated patients that were treated with VICTRELIS combination therapy compared with peginterferon and ribavirin alone were: fatigue (58 vs. 59 percent), anemia (50 vs. 30 percent), nausea (46 vs. 42 percent), dysgeusia (35 vs. 16 percent), respectively. The incidence of these adverse reactions in previously untreated patients that were treated with VICTRELIS combination therapy compared with peginterferon and ribavirin alone were: fatigue (55 vs. 50 percent), anemia (45 vs. 20 percent), nausea (43 vs. 38 percent), dysgeusia (44 vs. 11 percent), 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.

Please see prescribing information at: http://www.merck.com/product/usa/pi_circulars/v/victrelis/victrelis_pi.pdf.

Dosing and administration

VICTRELIS must be administered in combination with peginterferon alfa and ribavirin. Therapy is initiated with peginterferon alfa and ribavirin for 4 weeks. Beginning in treatment week 5, VICTRELIS is added at a dose of 800 mg (four 200 mg capsules) orally three times daily (every 7-9 hours) with food (a meal or light snack). Based on the patient's virus (HCV-RNA) levels at treatment weeks 8, 12 and 24, dosing is adjusted using the following response-guided therapy guidelines.

Treatment-naive patients: Patients who are undetectable at treatment weeks 8 and 24 complete all therapy at treatment week 28. Patients who are detectable at treatment week 8, but undetectable at treatment week 24, complete VICTRELIS at treatment week 36 and continue on peginterferon alfa and ribavirin alone until treatment week 48.

Treatment-failure patients: Patients (previous partial responders or relapsers) who are undetectable at treatment weeks 8 and 24 complete all therapy at treatment week 36. Patients who are detectable at treatment week 8, but undetectable at treatment week 24, complete VICTRELIS at treatment week 36 and continue on peginterferon alfa and ribavirin alone until treatment week 48. Response-guided therapy was not studied in treatment-failure patients who had less than a 2 log decrease in virus (HCV-RNA) at treatment week 12 of prior treatment (null responders). If treated, these patients should receive 4 weeks of peginterferon alfa and ribavirin followed by 44 weeks of VICTRELIS in combination with peginterferon alfa and ribavirin.

Patients with compensated cirrhosis should receive 4 weeks peginterferon alfa and ribavirin followed by 44 weeks of VICTRELIS in combination with peginterferon alfa and ribavirin.

Patients who have HCV-RNA results greater than or equal to 100 IU/mL at treatment week 12 discontinue the three-medicine regimen. Patients who have confirmed detectable HCV-RNA at treatment week 24 discontinue the three-medicine regimen.

The wholesale acquisition cost (WAC) of VICTRELIS per week is $1,100.

About Merck

Today's Merck is a global healthcare leader working to help the world be well. Merck is known as MSD outside the United States and Canada. Through our prescription medicines, vaccines, biologic therapies, and consumer care and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to healthcare through far-reaching policies, programs and partnerships. For more information, visit www.merck.com.

Forward-Looking Statement

This news release includes forward-looking statements within the meaning of the safe harbor provisions of the United States Private Securities Litigation Reform Act of 1995. Such statements may include, but are not limited to, statements about the benefits of the merger between Merck and Schering-Plough, including future financial and operating results, the combined company s plans, objectives, expectations and intentions and other statements that are not historical facts. Such statements are based upon the current beliefs and expectations of Merck s management and are subject to significant risks and uncertainties. Actual results may differ from those set forth in the forward-looking statements.

The following factors, among others, could cause actual results to differ from those set forth in the forward-looking statements: the possibility that the expected synergies from the merger of Merck and Schering-Plough will not be realized, or will not be realized within the expected time period; the impact of pharmaceutical industry regulation and health care legislation; the risk that the businesses will not be integrated successfully; disruption from the merger making it more difficult to maintain business and operational relationships; Merck s ability to accurately predict future market conditions; dependence on the effectiveness of Merck s patents and other protections for innovative products; the risk of new and changing regulation and health policies in the U.S. and internationally and the exposure to litigation and/or regulatory actions.

Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in Merck s 2010 Annual Report on Form 10-K and the company s other filings with the Securities and Exchange Commission (SEC) available at the SEC s Internet site (www.sec.gov).

The Prescribing Information and Medication Guide are available at: http://www.merck.com/product/usa/pi_circulars/v/victrelis/victrelis_pi.pdf and http://www.merck.com/product/usa/pi_circulars/v/victrelis/victrelis_mg.pdf.

____________________________
1 SVR, the protocol specified primary efficacy endpoint of the pivotal studies, is defined as achievement of undetectable HCV-RNA at 24 weeks after the end of treatment in all randomized patients treated with any study medication. Per protocol, if a patient did not have a 24-week post-treatment assessment, the patient s 12-week post-treatment assessment was utilized.

VICTRELIS" is a trademark of Schering Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, N.J., USA.

Revatio® and Adcirca® are trademarks of their respective owners and are not trademarks of Merck & Co., Inc., Whitehouse Station, N.J., USA.



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Robert Consalvo, 908-423-6595
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Source: Merck

Boceprevir Wins Favorable FDA Staff Review

MedPage Today covers FDA review of Boceprevir. Aside from the issues regarding Merck's definition of 'null responder', the predictive value of viral kinetics and the hemotologic issues with the drug, the only formal voting issue, however, is whether "the available data support approval" of boceprevir for treating HCV genotype 1 in combination with peginterferon and ribavirin.

Boceprevir Wins Favorable FDA Staff Review
By John Gever, Senior Editor, MedPage Today
Published: April 25, 2011

WASHINGTON -- The FDA's professional staff believes the investigational hepatitis C drug boceprevir (Victrelis) is effective and reasonably safe, according to a briefing document made public in advance of a Wednesday advisory committee meeting.

But before the agency approves the drug, it wants the panel's views on certain marketing claims that the drug's manufacturer, Merck, is proposing to make. These include the drug's efficacy in patients with "null" responses to the standard regimen of pegylated interferon and ribavirin as well as the benefits of so-called response-guided therapy.

The Antiviral Drugs Advisory Committee will also be asked to review risks of anemia and other hematologic abnormalities associated with boceprevir.

The drug is one of two hepatitis C virus (HCV) protease inhibitors that will be reviewed during a two-day meeting this week. The other is telaprevir -- no brand name has been proposed as yet -- which will have its day on Thursday.

The two drugs would be the first HCV protease inhibitors to reach the market. They have attracted major buzz among physicians and patients on the basis of excellent-looking clinical trial results, most recently from two of boceprevir's pivotal studies published in the New England Journal of Medicine last month.

These data suggest that adding one of the drugs to the standard peginterferon-ribavirin combination doubles or triples the sustained viral response rates.

For example, among treatment-naive patients in one of the boceprevir trials, 40% of a control group receiving the conventional regimen had a sustained response versus about 70% of patients with the protease inhibitor added.

A separate trial in patients with previous partial or unsustained responses to the standard regimen showed that 21% achieved a sustained response with a second round, whereas approximately 60% did with the addition of boceprevir.

In the briefing paper prepared for Wednesday's panel meeting, the FDA staff reviewers could find little to fault in these data.

But they did question Merck's arguments in favor of "response-guided therapy," particularly in African-American patients and raised concerns about the drug's hematologic side effects.

The core treatment regimen with boceprevir tested in the trials included a four-week lead-in period with peginterferon and ribavirin with boceprevir then added for 44 weeks. But some of the trials also included a regimen in which the duration of boceprevir treatment could be extended based on viral responses after eight and 24 weeks.

In particular, Merck would like the drug's label to allow longer treatment for patients with detectable HCV RNA at eight weeks but who achieve a full virologic response at 24 weeks, as some data suggested that such a regimen improves the sustained response rate.

But the FDA staff reviewers pointed to data in one of the trials indicating a slightly lower sustained-response rate in previous treatment failures receiving the response-guided therapy compared with fixed-duration treatment (59% versus 66%).

They also noted that black participants in a study of treatment-naive patients also had a lower sustained-response rate with response-guided therapy (42% versus 53%).

"The 11% numerical difference ... is of some concern and will be an issue for discussion," the briefing paper said.

Another issue is whether a proposed indication for patients who completely failed previous peginterferon-ribavirin therapy is justified, considering that such patients were excluded from trials of previously treated patients.

Merck is arguing that its major trial in treatment-naive patients included null responders, identified as those with negligible responses during the lead-in with standard therapy, and the drug's efficacy in this population can be gauged from those results.

However, the FDA reviewers indicated that responses at week four do not perfectly predict who will ultimately respond. The lack of a trial designed expressly to test the drug in null responders "raises questions about using [standard therapy] lead-in responses as a surrogate," they wrote in the briefing document.

About a quarter of the briefing document was devoted to boceprevir's adverse hematologic effects, primarily anemia but also including neutropenia and thrombocytopenia.

In the drug's two main phase III trials, half the patients taking the drug had nadir hemoglobin values of 10 g/dL or below and more than 40% required erythropoietin therapy -- with both rates about twice those seen in the control groups.

The other hematologic effects were far less common, but still a potential concern, according the briefing document.

Counting all cases, the incidence of neutropenia was about the same with or without boceprevir, but the drug was associated with a greater rate of serious cases. Eight of 1,057 patients taking the drug discontinued the study because of neutropenia compared with none in the control groups.

Similarly, severe thrombocytopenia was seen in 15 boceprevir-treated patients compared with three control patients.

The FDA plans to ask the advisory panel to comment on these adverse events, as well as to discuss postmarketing studies that Merck should conduct if the product is approved.

The only formal voting issue, however, is whether "the available data support approval" of boceprevir for treating HCV genotype 1 in combination with peginterferon and ribavirin.