| |
FDA Panel Votes 18-0 Recommending Boceprevir Approval for Treatment of HCV in Genotype 1 Patients - Merck press release
|
| |
| |
from Jules: of course this was the big news. The mantra at the hearing was this is the new fantastic era of HCV drug treatment, this is great, and tomorrow the FDA panel is expected to put the same stamp of approval on the Vertex HCV protease telaprevir. Of interest today was the focus of discussion on 2 key issues: should boceprevir get an indication to treat null responders. During the FDA presentation it was apparent they supported this but the panel appeared to push back as opinions on this appeared very mixed among the committee members. The question is that null responders were not prospectively studied in the phase 3 pivotal boceprevir studies but a post study analysis was performed by the FDA itself showing that study patients who received a peginterferon/rbv lead-in, that after 4 weeks the patients with <1 log and also patients with <0.5 log reduction in viral load who then added boceprevir about 35% with a 1 log reduction achieved SVR and patients with a 0.5 log reduction had a 28% SVR. The criticism was this is a post-hoc analysis, not prospective, but the FDA did this analysis. And in the Vertex telaprevir prospective study null responders also achieved a 32% SVR rate so the boceprevir number fits with that. So there was a controversial discussion about this among the committee members with a fairly even split on the issue I think. See my other report where I discuss this further: critics said a week 4 1 log viral load reduction may also be associated with either a 2 lof reduction at week 12 thus the patient may not really be a null responder or the patient may have no further reduction at week 12. Merck presented data that patients without 12 week 2 log reduction with a 4 week 1 log reduction did show a 32% SVR rate. In the end the FDA will decide whether to grant the indication or not. But tomorrow Vertex will ask for the same indication and if the FDA was willing to support the boceprevir request I think they will support the Vertex request. I also spoke with a lot of attendees at the meeting and there was controversy among them as well about whether or not boceprevir should get the indication. The lesson for the other drug companies is to make sure they do a prospective study of null responders. The other big question that came up today was how long to treat difficult-to-treat patient populations like cirrhotics, blacks etc. Should Response Guided therapy be ok for them because these tough to treat patients generally did better with 48 weeks therapy than with a shorter duration of therapy and again this was controversial with opinions split among the committee members. Again see my other report where I dscuss this further. So we will see how the FDA rules on this and how the committee responds to the Vertex null responder data tomorrow. Both drugs will be approved and I expect be in the pharmacy as quickly as the companies can make it happen. There was quite a lot of discussion today about the side effects of boceprevir, it appears to be associated with increased rates of anemia causing increased use of EPO which can also be associated with toxicities. So managing patients who get anemia can be difficult but the committee rightfully agreed this is manageable and for the first time we have such a fantastic leap in treatment success with SVR rates of about 67% with boceprevir in treatment-naives & 59-66% in treatment-experienced patients and for 44% of patients in the naive study they were eligible for 28 weeks shortened therapy compared to 48 weeks, standard for genotype 1 patients.
VICTRELIS™ (boceprevir) Unanimously Recommended for Approval by FDA Advisory Committee for Treatment of Chronic HCV Genotype 1 Infection - Merck press release
Wednesday, 27 April 2011 17:03
WHITEHOUSE STATION, N.J.-( Business Wire )-
Merck (NYSE:MRK) (known as MSD outside the United States and Canada) announced today that the Antiviral Drugs Advisory Committee of the U.S. Food and Drug Administration (FDA) voted unanimously that the available data support approval of Merck's investigational medicine VICTRELIS™ (boceprevir) for the treatment of patients with chronic hepatitis C virus (HCV) genotype 1 infection in combination with current standard therapy. VICTRELIS is one of a new class of medicines known as HCV protease inhibitors being evaluated by the FDA for the treatment of chronic HCV genotype 1 infection in adult patients with compensated liver disease who are previously untreated or who have failed previous therapy.
The committeeÕs recommendation will be considered by the FDA in its review of the New Drug Application for VICTRELIS. The FDA is not bound by the committeeÕs guidance, but takes its advice into consideration when reviewing investigational medicines. The company anticipates FDA action on VICTRELIS by mid-May.
ÒThe positive recommendation brings us one step closer to bringing VICTRELIS to men and women who need it, and reinforces our ongoing commitment to developing innovative therapies to treat chronic hepatitis C," said Peter S. Kim, Ph.D., president, Merck Research Laboratories. "We're pleased with the panel's decision and look forward to working with the FDA as it continues to evaluate the application for VICTRELIS."
The FDA granted priority review status for VICTRELIS, a designation for investigational medicines that address unmet medical needs. Additionally, the European Medicines Agency (EMA) has accepted the Marketing Authorization Application (MAA) for VICTRELIS for accelerated assessment.
The panel reviewed the results from the Phase III clinical study program for VICTRELIS; the clinical trials HCV SPRINT-2 and HCV RESPOND-2 included approximately 1,500 patients with chronic HCV genotype 1 infection, the most common form of the virus in the United States and most difficult to treat. Data that were discussed involved 1,097 treatment-na•ve patients (HCV SPRINT-2) and 403 patients who failed previous therapy (HCV RESPOND-2). HCV SPRINT-2 included a separate analysis of results in African-American patients, a patient population that typically does not respond well to standard therapy. Results from HCV SPRINT-2 and HCV RESPOND-2 were published in the March 31 issue of the New England Journal of Medicine.
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. Extensive research efforts are underway to develop oral therapies that bring innovation to viral hepatitis treatment.
--------------
FDA Panel Recommends Approval Of Merck's Hepatitis C Drug
from Jules: the big news of course is the FDA committee recommended 18-0 to approve boceprevir.
WASHINGTON (Dow Jones)--A Food and Drug Administration panel backed the use of Merck & Co.'s (MRK) hepatitis C drug boceprevir, calling the product a game-changing advance in the treatment of the disease.
The panel of non-FDA medical experts voted 18-0 in favor of a question that asked whether the available data support approval of the product in combination with other hepatitis C drugs, pegylated interferon and ribavirin. The vote amounts to a recommendation that the agency approve boceprevir, which Merck has proposed selling under the brand name Victrelis.
Indeed, FDA staff suggested the agency was leaning toward approving boceprevir and a similar product telaprevir from Vertex Pharmaceuticals Inc. (VRTX) that will be reviewed Thursday by the same FDA panel.
Debra Birkrant, the director of FDA's antiviral-drugs division, said the products appear to increase sustained virologic response rates, or essentially the cure rate "to more than 30% above what we have today." Both drugs are known as protease inhibitors, which are designed to block an enzyme that helps the hepatitis C virus replicate. Studies showed the drugs worked better when added to existing treatments and in many cases significantly shortened the total treatment time. Currently patients need almost a year of therapy.
One study involving boceprevir found that 66% of patients receiving that drug in addition to pegylated interferon and ribavirin had a sustained virologic response compared to 38% who received the current, standard therapy of pegylated interferon and ribavirin.
FDA staff said the panel meeting was primarily being held for advice on writing boceprevir's drug label, which instructs physicians on how to properly use products. One issue is how long to treat patients who don't appear to be responding to treatment and how to treat African-Americans who didn't respond as well other patients in clinical trials.
Hepatitis C is a liver disease caused by infection with the hepatitis C virus, which is transmitted through contaminated blood. The infection can cause liver failure, liver cancer and is the leading cause of liver transplants, FDA said. About 3.2 million Americans are infected with hepatitis C.
-----------------
FDA panel recommends approval of new hepatitis C drug
April 27th, 2011
CNN blogs 06:38 PM ET
A new treatment for hepatitis C could soon be on the market if the Food and Drug Administration takes the advice of an advisory committee. The committee unanimously approved the first of two new drugs to treat chronic hepatitis C genotype 1 infection. Hepatitis C is a chronic viral disease that causes inflammation and swelling of the liver.
The drug, boceprevir, is a new class of protease inhibitor manufactured by pharmaceutical giant Merck & Co., and would be used in combination with ribavirin and peginterferon-the current standard of care. Boceprevir prevents the virus from replicating, and studies show the three-drug cocktail is more effective than the two-drug regimen.
According to Merck, about 66% of study patients that hadn't been treated or did not respond well to current treatment responded well to boceprevir.
The FDA's outside panel of experts considered the risks and benefits of the drug and determined the benefits far outweigh the risks.
"The benefit for the people who do achieve sustained virologic response is fantastic," said Dr. Elizabeth Connick, University of Colorado Denver. "This is a miraculous advance."
"The risks are not trivial, but we do know how to manage these risks. Still, there is a lot to learn about using these drugs appropriately," said Dr. Thomas Giordano of Baylor College of Medicine.
"This is going to be a real game changer for our hepatitis C practices, " said Dr. Barbara McGovern, Tufts University School of Medicine. "I can't wait to get back and talk to my patients about it."
Even hard-to-treat patients like African Americans, and people with HIV and diabetes responded extremely well to the boceprevir combination therapy.
Dr. Nizar Zein, section head of hepatology at the Cleveland Clinic says the disease is of epidemic proportions and quite costly. Zein say the new medication will usher in a very important new era for treating the disease.
"We can now say for the first time that we can cure hepatitis C," Zein said. "We are talking about complete cure, cure for life. Several studies have shown that once you achieve that endpoint, the sustained virological response, you will not get hepatitis C ever again and the risk of getting cirrhosis, needing liver transplant will go down substantially."
But this is a powerful drug and a major concern is that drug resistance can develop in patients very quickly if the medication is not taken properly. The proposed dosage is 800 mg three times a day with food.
Treatment can be individualized but Zein says both doctors and patients need to be educated and clear about when and how this drug is to be taken. "If used inappropriately, the virus will rapidly develop resistance to these medications - rapidly, I mean 24 to 48 hours."
Close attention was paid to the drug's side effects. The most common, according to Merck included anemia, abnormally low white blood cell count, fatigue, nausea, headache, hair loss and an impaired sense of taste.
According to FDA's Dr. Poonam Mishra, the most notable safety concern is the additional decrease in hemoglobin- the protein in red blood cells that carries oxygen. Hemoglobin levels lower than normal could mean anemia, bleeding or a number of other conditions. Mishra said anemia was managed effectively during the clinical trials and was reversible after the drug was discontinued. Only a few serious and life-threatening infections were reported.
Martha Saly, director of the National Viral Hepatitis Roundtable, who learned that she had hepatitis C in 1998 and was successfully treated with interferon, said even though treatment will be extremely challenging, for the first time she has hope for a universal cure.
"I believe that approval of these drugs will be the biggest thing that has happened in years," Saly said. "I am hopeful that a shortened course of treatment for many patients will equate with a greater ability to tolerate the drugs and manage the side effects, but I fear that the issue of compliance with strict medication regimens might affect treatment success."
Saly says the drugs will help few patients if awareness of the hepatitis C epidemic, improved screening and affordable access to care are not addressed.
More than 3.2 million Americans have hepatitis C, the most common bloodborne infection in the country. According to the Centers for Disease Control and Prevention about 10,000 people die of liver disease and liver cancer directly related to hepatitis C each year. It's usually caused by contact with infected blood products, though it can also be transmitted sexually or contracted through IV-drug use.
The disease is the leading cause of liver cirrhosis, and the need for liver transplants in the United States. Cirrhosis is when scar tissue forms in the liver, replacing healthy liver tissue and blocking blood flow through the liver.
Symptoms included abdominal pain, dark urine, fever, and jaundice but most people don't have symptoms until liver damage has occurred which, according to the National Institute of Diabetes and Digestive and Kidney Diseases , could be 10 years or more.
The FDA is not bound by their advisory committee recommendations but often follow their advice. Merck says it anticipate FDA action on boceprevir by mid-May.
"The positive recommendation brings us one step closer to bringing Victrelis (boceprevir) to men and women who need it, and reinforces our ongoing commitment to developing innovative therapies to treat chronic hepatitis C," said Peter S. Kim, Ph.D., president, Merck Research Laboratories.
On Thursday, the panel will make recommendations on Vertex Pharmaceuticals' telaprevir, the other new drug in this class. The FDA released a preliminary review of telaprevir saying clinical trials showed, when combined with standard treatments, it was more effective than those therapies. Vertex is hoping to beat Merck to the finish line by winning FDA approval first.
|
|
| |
| |
|
|
|
