January 6, 2011

Some Emerging HCV Therapies

By Sean R. Hosein
From Canadian AIDS Treatment Information Exchange

December 23, 2010

Underlying some of the research with new anti-HCV agents is the hope that peginterferon, and eventually ribavirin, can eventually be replaced with more tolerable agents. This may not be possible in the immediate future, but some researchers hope that over the next five years perhaps less time spent taking peginterferon and ribavirin may be a possibility for future HCV treatment regimens.

Anti-HCV drugs under development can be divided into several groups, or classes, depending on how they work.

Protease Inhibitors

HCV needs enzymes called NS3/4A proteases that help HCV-infected cells produce new copies of HCV. These enzymes also appear to suppress the ability of infected cells to alert other cells about attack by HCV. So HCV protease inhibitors could have several benefits.

Drug companies often seek to get their drugs first approved by regulatory authorities in the United States, followed by the European Union and then Canada, Australia, Japan and other high-income countries. This is because the U.S. and the EU have large, relatively wealthy populations and present opportunities for sales and profit for drug companies. Also, it is likely that new therapies for HCV will first be approved for use in HCV mono-infection because there are more cases of mono-infection than co-infection and new therapies were initially developed for treating HCV mono-infection.

The two new anti-HCV drugs that are most likely to be approved in the U.S. are the protease inhibitors telaprevir (made by Vertex Pharmaceuticals) and boceprevir (made by Merck).

Both of these drugs have shown powerful anti-HCV activity in clinical trials of HCV mono-infection when taken as part of regimens that contain peginterferon and ribavirin. These protease inhibitors are also useful in people who have previously been treated with standard HCV therapy (peginterferon and ribavirin) but who did not respond.

Boceprevir and telaprevir are expected to be approved in the United States in 2011, with approval in the EU probably occurring in the same year. These drugs are expected to be approved in Canada in 2012.

Both of these protease inhibitors must be taken three times daily and can have side effects such as anemia. Therefore, interest in other HCV protease inhibitors under development -- such as TMC 435350 (made by Tibotec) and GS 9256 (made by Gilead Sciences) -- as well as other drugs by other companies is intense.

Polymerase Inhibitors

These drugs represent another class of anti-HCV agents and interfere with an enzyme called polymerase (hence their name). Examples of polymerase inhibitors include RG7128 and RG1628 (being developed by Hoffmann-La Roche), ABT 072 and ABT 333 (being developed by Abbott) and GS 9190 (being developed by Gilead Sciences).

Cyclophillin Inhibitors

Cyclophillins are receptors for the compound cyclosporine and are found inside of cells. The role of cyclophillins in cells is not fully understood, but these receptors may play a role in infections with viruses such as HIV and HCV. By impairing the activity of these receptors, HCV cyclophillin inhibitors can reduce the ability of HCV-infected cells to produce new viruses. Alisporivir (being developed by Novartis) is an example of a cyclophillin inhibitor.

There are other classes of anti-HCV drugs under development but they are not as far advanced as those previously mentioned.

Future Approaches to Therapy

In the treatment of HIV infection, using a combination of drugs from several classes is now the norm. Combining classes reduces the risk of HIV developing resistance to therapy. The same principle will likely apply to HCV.

Five years from now there should be a full suite of anti-HCV drugs available from different classes. When that happens, combination therapy for HCV might then include drugs from different classes and peginterferon-free regimens might finally be possible.

Gelman MA, Glenn JS. Mixing the right hepatitis C inhibitor cocktail. Trends in Molecular Medicine. 2010. In press.


Reporting could help stop hepatitis C

By Lori Nerbonne / For the Monitor
January 6, 2011
Thank you to Meg Heckman for "My Epidemic," her moving, candid and sobering December series on hepatitis C (concordmonitor.com/hcv). She reminds us that although it is a silent disease in symptoms, it wreaks havoc with victims' lives. Her selflessness in sharing the personal details of her journey is sure to be far-reaching and gives a voice to so many silent victims.
Meg's story reminded me of another hepatitis C victim I had the pleasure of meeting last year at a workshop I attended at the Centers for Disease Control. Dr. Evelyn Mc-Knight, a lovely soft-spoken audiologist from Fremont, Neb., had come to tell about her life-changing diagnosis of hepatitis C that began in 2001.

While undergoing treatment for stage 3 breast cancer at a local oncology clinic, Evelyn's routine blood testing came back positive for Hepatitis C. Knowing she had none of the risk factors caused confusion and alarm. Shortly after, her husband Tom, a local physician, began noticing that some of his patients had an elevated liver enzyme that is sometimes consistent with hepatitis, so he had them tested. All four tested positive for hep C. These same patients were all being treated for cancer at the same oncology clinic as his wife Evelyn.

Eventually the largest outbreak (99 patients) of hepatitis C in a U.S. health care facility was discovered by the determination of a caring husband and physician, and through sheer coincidence. Since then, several other, much larger health care facility outbreaks have been discovered across the country. Inappropriate and dangerous reuse of common medical equipment like syringes and medication vials are the usual culprits.

Evelyn now works as a passionate patient safety advocate and, with the CDC, has launched a national campaign to educate health-care providers and patients about safe injection practices (honoreform.org).

Most of these outbreaks have occurred in outpatient settings, but no health-care facility is immune. But here's the catch: The trigger for an investigation into these outbreaks often occurs when positive hepatitis C blood tests are reported to a centralized lab at the state public health department. Many states require this type of reporting. New Hampshire does not. This means that a cluster of positive tests or a major outbreak in a health-care facility in New Hampshire would likely go unnoticed, putting many unknowing patients at risk for years.

As a recent Monitor editorial underscores, it will take public health, academic, legislative and health-care leaders from across the state to tackle this problem. For many communicable diseases like hepatitis C, a public health model that includes prevention, early detection, tracking and early intervention would not only save billions of our health-care dollars, but human suffering and many precious lives.

(Lori Nerbonne of Bow is the founder of New Hampshire Patient Voices.)

Also See: My Epidemic.....Shared and Written by Meg Heckman of the Concord Monitor

Merck Beats Vertex to FDA Hep C Filing

By Adam Feuerstein
01/06/11 - 10:07 AM EST

WHITEHOUSE STATION, NJ (TheStreet) --In the race to market the first next-generation treatment for hepatitis C, Merck(MRK_) is out to an early lead.

Or, as my kids would so delicately put it: "Vertex Pharmaceuticals(VRTX_), you just got burned!!!"

The U.S. Food and Drug Administration accepted Merck's approval filing for its hepatitis C drug boceprevir, the company said Thursday. The news from Merck is a bit of a surprise since the company hadn't previously announced or confirmed that boceprevir had been filed with U.S. regulators.

It's also a tad embarrassing for Vertex, which is still waiting to hear back from FDA about the acceptance of the approval filing for telaprevir, its competing hepatitis C drug. That news should come by Jan. 24, based on Vertex's previous announcement that it filed the drug's application on Nov. 23.

Still, it seems as if Merck beat Vertex to the FDA by at least two weeks.

Merck's boceprevir, therefore, has a chance to grab bragging rights as the first, next-generation hepatitis C drug approved by FDA.

If both drugs are approved, boceprevir could be on the market by the second week of May, or approximately two to three weeks before Vertex has a chance to do the same with telaprevir.

In the grand scheme of things, a two-week head start is trivial. But given Vertex's reputation for supreme confidence (some would say cockiness), the fact that slothy Big Pharma giant Merck has taken the early lead in the hepatitis C drug race is a surprising comeuppance.

Vertex shares were down 19 cents to $36.68 in early Thursday trading.

A Merck spokesman would not confirm the exact FDA filing date for boceprevir. A Vertex spokesman said, "We expect to hear from the FDA this month regarding our request for priority review."

Cheer up, Vertex. The race to approval for a new hepatitis C drug is really just the starting point. What really matters is how each drug fares in the commercial market. Merck's early lead now may not matter much once doctors and patients have a choice of which drug to use.

Also See:
-- Merck scoots past Vertex in blockbuster race for hep C drug approval
-- Boceprevir, Merck’s Investigational Oral Hepatitis C Protease Inhibitor, Receives FDA Priority Review and EMA Accelerated Assessment

Merck scoots past Vertex in blockbuster race for hep C drug approval

January 6, 2011 — 12:23pm ET
By John Carroll

Merck ($MRK) has stolen a small lead in its hot race with Vertex ($VRTX) for regulatory approval of a new hepatitis C treatment. The pharma giant says that regulators in the U.S. as well as Europe have accepted its applications for boceprevir. And the FDA plans on an expedited, six month review.

Vertex, meanwhile, is still waiting for confirmation from the FDA on its closely-watched application for telaprevir, which it confidently expects will win approval this year after presenting a mountain of promising late-stage data on its behalf. Word should arrive in the next couple of weeks, though, which will help the market handicappers estimate where these two drug prospects are likely to land later in 2011.

"We are pleased that the FDA and EMA have accepted boceprevir for expedited review. Our goal is to be able to bring forward a new treatment option for patients living with chronic hepatitis C, and we are now closer to that goal," said Dr. Peter Kim, president, Merck Research Laboratories.

There's no such thing as a sure thing in drug development, but both drugs are considered odds-on favorites for an approval. And they promise to shake up the hep C treatment field in short order.


Also See: Boceprevir, Merck’s Investigational Oral Hepatitis C Protease Inhibitor, Receives FDA Priority Review and EMA Accelerated Assessment

Pharmasset says HCV drugs show promise

Thu Jan 6, 2011 7:48am EST

* PSI-7977 shows rapid viral suppression
* PSI-938 found to be well tolerated

Jan 6 (Reuters) - Pharmasset Inc (VRUS.O) said interim analyses of clinical studies of its two drugs for chronic hepatitis C showed promise.

A mid-stage study of the drug, codenamed PSI-7977, showed rapid viral suppression with all patients remaining below limit of detection at the end of treatment. No serious adverse events were reported.

The drug was granted "fast track" designation in August. Fast-track status is designed to expedite the review of drugs to treat serious diseases and fill unmet medical needs. [id:nSGE67B0JZ]

The company said it expects to start a 24-week mid-stage study of the drug in the second quarter of 2011.

An early-stage study of the drug, codenamed PSI-938, as a monotherapy was found to be safe and well-tolerated, Pharmasset said.

The Princeton, New Jersey-based company's shares, which have risen 50 percent in the last three months, closed at $46.59 on Wednesday on Nasdaq. (Reporting by Shravya Jain in Bangalore; Editing by Sriraj Kalluvila)


Thursday, January 06, 2011

Pharmasset Reports Interim Study Results For Its Hepatitis C Drugs

Pharmasset (NASDAQ:VRUS) announced today interim results for the Phase 2b study for its PSI-7977 drug and the Phase 1 study for its PSI-938 drug. Both drugs are designed to treat Hepatitis C.

The Phase 2b study consisted of evaluating the effects of various PSI-7977 dosages in patients with Hepatitis C genotype 1, 2 or 3. The patients also received antiviral drugs commonly used to fight Hepatitis C.

Hepatitis genotype 1 patients received dosages of PSI-7977 and antiviral drugs over a 12-week period followed by 12 or 36 weeks of just antiviral drugs. Heptatitis genotype 2 and 3 patients received dosages of PSI-7977 and antiviral drugs over 12 weeks with no therapy afterward.

For the patients with Hepatitis C genotype 2 or 3, the data shows no serious adverse events and no discontinuations due to adverse events, the New Jersey-based company said. All patients showed viral suppression.

Results for the patients with Hepatitis C genotype 1 will be released in the second quarter of 2011, the company said.

During the second quarter of 2011, the company also expect to initiate a 24-week Phase 2b study of PSI-7977 with pegylated interferon and ribavirin.

In a separate Phase 1 study, the company also tested the PSI-938, a Hepatitis drug in a different chemical form than the PSI-7977.

Over a period of 14 days, patients were given dosages of only PSI-938 and showed no serious adverse events as well as no dose modifications or discontinuations, the company said. Also, the patients did not see an increase in the severity of viral infection while on therapy.

PSI-938 will also be tested in combination with PSI-7977, with the results scheduled to be reported sometime this quarter.


Boceprevir, Merck’s Investigational Oral Hepatitis C Protease Inhibitor, Receives FDA Priority Review and EMA Accelerated Assessment

January 06, 2011 08:00 AM Eastern Time

WHITEHOUSE STATION, N.J.--(BUSINESS WIRE)--Merck, known as MSD outside the United States and Canada, announced today that regulatory applications for boceprevir, Merck's investigational oral hepatitis C virus (HCV) protease inhibitor, were submitted in 2010 and have been accepted for expedited review in both the U.S. and the European Union.

The U.S. Food and Drug Administration (FDA) granted the New Drug Application (NDA) for boceprevir Priority Review status, a designation given to drugs that offer major advances in treatment, or provide a treatment where no adequate therapy exists. FDA's goal for completing a Priority Review is six months.

Additionally, the European Medicines Agency (EMA) accepted the Marketing Authorization Application (MAA) for boceprevir for accelerated assessment. Accelerated assessment is available for products that respond to unmet medical needs or represent a significant improvement over current treatment options within a major public health interest such as treatment of hepatitis C virus infection.

Data in the NDA and MAA have been provided in support of the proposed use of boceprevir for the treatment of chronic HCV genotype 1 infection, in combination with standard therapy, in adult patients with compensated liver disease who are previously untreated or who have failed previous therapy.

"We are pleased that the FDA and EMA have accepted boceprevir for expedited review. Our goal is to be able to bring forward a new treatment option for patients living with chronic hepatitis C, and we are now closer to that goal,” said Dr. Peter S. Kim, Ph.D., president, Merck Research Laboratories.

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. Extensive research efforts are underway to develop differentiated oral therapies that bring innovation to viral hepatitis care.

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 http://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 2009 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 (http://www.sec.gov/).

Ian McConnell, 908-423-3046
Robert Consalvo, 908-295-0928
Joe Romanelli, 908-423-5088