Called 'watershed' research, study reports success with oral meds
By Mary Brophy Marcus
HealthDay Reporter
WEDNESDAY, Jan. 18 (HealthDay News) -- A new cocktail of two investigational drugs appears to have successfully cleared the hepatitis C virus in people who don't respond to standard treatment.
What's more, the approach seems to work without the need for injections with interferon alpha, an onerous medication that causes serious side effects in many patients.
Scientists from seven U.S. medical centers and drug maker Bristol-Myers Squibb published the small study in the Jan. 19 issue of the New England Journal of Medicine that is being heralded as "landmark" research.
"We saw a sustained virologic response -- the virus was undetectable in the patients -- during treatment and remained undetectable after the drugs were stopped," said study author Dr. Anna Lok, director of clinical hepatology at the University of Michigan Medical School in Ann Arbor.
Hepatitis C virus, spread through contact with contaminated blood, is the most common form of the virus and affects 180 million people globally, including 4.1 million Americans. It's the leading cause of chronic liver disease, and can lead to liver cancer. The standard treatment includes injections of the antiviral drug interferon alpha, which isn't tolerated well by everyone, said Dr. Andrew Muir, director of gastroenterology and hepatology research at the Duke Clinical Research Institute. Its many side effects include flu-like symptoms, fatigue, fever and depression.
"Many patients cannot complete treatment or decide not to take treatment because of interferon alpha," Muir said.
The study had two arms, said Lok. A group of 10 patients received four medications, including the two investigational drugs, the antivirals daclatasvir and asunaprevir, along with the standard treatment combination of interferon and ribavirin. The other arm of the study included 11 patients who received only the two investigational drugs. Both groups underwent treatment for 24 weeks.
The 10 patients on the four-drug regimen experienced a sustained virologic response with undetectable virus at the end of treatment and again at 12 weeks beyond their treatment, the researchers reported. In the two-drug group, four of the 11 patients also had undetectable levels of the hepatitis C virus in their blood 12 weeks after treatment ended.
All of the patients were infected with genotype 1, the most common type of hepatitis C virus in the United States, and had not responded to previous treatment with interferon and ribavirin, said Lok.
"The four-drug arm was very impressive. These patients had not shown a response before and now we get a 90 to 100 percent rate of sustained response," said Lok.
She said even though only four patients in the two-drug group reached a sustained response, this is the first study to show it can be achieved without interferon or ribavirin.
"Clearly, this is the biggest development in hepatitis C research in a very long time," said Dr. Raymond Chung, director of hepatology at Massachusetts General Hospital in Boston, who wrote an accompanying editorial in the same issue of the journal. "It has enormous implications for our ability to treat many more patients with regimens that are significantly more tolerable."
The most common side effects reported were headache, diarrhea, nausea and fatigue, the study authors said.
Chung called the study "a watershed moment" because it suggests that an interferon-free treatment is possible. "The conventional wisdom for quite some time has been that hepatitis C would likely not be curable without an interferon backbone."
Duke's Dr. Muir added, "The study is also exceptional because it included patients we would describe as the most difficult to treat." Their viral load did not go down very much when they underwent interferon and ribavirin treatment in the past.
The new drugs are not FDA-approved yet, but a number of trials are under way, said Chung, who believes an interferon-sparing regimen is only a few years away. "It is not beyond belief that we'll have an all-oral therapy available as early as 2015. That's the pace it's going right now," he said.
"There's certainly hope," said Lok, who noted that the research was funded by drug maker Bristol-Myers Squibb.
More information
The U.S. National Institutes of Health has more on clinical trials for hepatitis C.
SOURCES: Anna Lok, M.D., director, clinical hepatology, University of Michigan Medical School, Ann Arbor; Andrew Muir, M.D., director, gastroenterology and hepatology research, Duke Clinical Research Institute, Durham, N.C.; Raymond Chung, M.D., chief, hepatology, Massachusetts General Hospital, Boston; Jan. 19, 2012, New England Journal of Medicine
Last Updated: Jan. 18, 2012
Copyright © 2012 HealthDay. All rights reserved.
Bristol-Myers Squibb Company (NYSE: BMY) today announced the full results, published in the New England Journal of Medicine, from a Phase II clinical trial in patients with hepatitis C virus (HCV) genotype 1 who had not responded to prior therapy with PEG-interferon alfa and ribavirin ('null responders'). The study demonstrated that its primary endpoint of the achievement of sustained virologic response 12-weeks post-treatment (SVR12) is possible with a direct-acting antiviral (DAA)-only combination containing daclatasvir and asunaprevir (4/11 patients, including two of two patients infected with HCV genotype 1b). This study was the first study to demonstrate the possibility that hepatitis C can be cured (defined as sustained virologic response 48 weeks post-treatment or SVR48) without the use of interferon. The study also demonstrated that 100 percent (10/10) of these difficult-to-treat patients dosed with quadruple therapy containing daclatasvir and asunaprevir in combination with PEG-Interferon alfa and ribavirin achieved SVR12.
“Even with the recent approval of two protease inhibitors, treatment of hepatitis C patients who have not responded to PEG-interferon alfa and ribavirin has limited success. Because of this high unmet medical need, there is a necessity for new combination regimens that can increase response rates in null responders”In this study there were no serious adverse events on treatment or discontinuations due to adverse events. Diarrhea was the most common adverse event in both groups (73% and 70%).
"Even with the recent approval of two protease inhibitors, treatment of hepatitis C patients who have not responded to PEG-interferon alfa and ribavirin has limited success. Because of this high unmet medical need, there is a necessity for new combination regimens that can increase response rates in null responders," said lead investigator Anna Lok, MD, FRCP, director of clinical hepatology and professor in the department of internal medicine at the University of Michigan Medical School in Ann Arbor. "The data seen in this study with Bristol-Myers Squibb's investigational DAAs daclatasvir and asunaprevir, either as DAA-only therapy or as part of quadruple therapy, are encouraging as we work to advance hepatitis C therapy for this difficult-to-treat patient population. This study also shows for the very first time that sustained viral responses can be achieved without the use of interferon and ribavirin."
Daclatasvir is the first NS5A replication complex inhibitor to be investigated in HCV clinical trials and is currently in Phase III development. Asunaprevir is an investigational, oral, selective NS3 protease inhibitor.
Source Bristol-Myers Squibb
Daclatasvir is the first NS5A replication complex inhibitor to be investigated in HCV clinical trials and is currently in Phase III development. Asunaprevir is an investigational, oral, selective NS3 protease inhibitor.
Source Bristol-Myers Squibb
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