Published: Oct 8, 2013
By Michael Smith, North American Correspondent, MedPage Today
Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner
Action Points
- Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
- A triple-drug regimen without interferon and ribavirin achieved very high success rates in treatment-naive hepatitis C genotype 1 patients.
SAN FRANCISCO -- A triple-drug regimen for hepatitis C (HCV) led to a cure in about 90% of patients without using elements of the standard therapy for the disease, a researcher said.
In a randomized phase II trial, the combination of so-called "direct-acting agents" completely knocked out the virus in between 89% and 94% of patients 12 weeks after the end of therapy, according to Maribel Rodriguez-Torres, MD, of the Fundación de Investigación in San Juan, Puerto Rico.
The combination of investigational drugs was "generally well tolerated" in patients with the difficult-to-treat genotype 1 of the virus, Rodriguez-Torres reported at the IDWeek meeting here.
For years, standard HCV therapy has included pegylated interferon alfa and ribavirin, drugs that are both difficult to take and in some cases dangerous.
And that therapy leads to sustained virologic responses in no more than half of patients with genotype 1, although adding either of the approved direct-acting agents – telaprevir (Incivek) and boceprevir (Victrelis) – improves those outcomes markedly.
So researchers are seeking regimens that both target the virus directly -- interferon and ribavirin do not -- and have better outcomes.
In this case, they are testing once-daily daclatasvir, an NS5A replication complex inhibitor; twice daily asunaprevir, an NS3 protease inhibitor; and the as-yet-unnamed non-nucleoside NS5B polymerase inhibitor, BMS-791325, given twice a day.
The study is encouraging for those hoping that interferon- and ribavirin-free regimens will soon be approved, according to Arthur Kim, MD, of Massachusetts General Hospital in Boston, who was not involved in the study but who moderated the session at which it was presented.
"Once you are able to attack multiple viral targets," he told MedPage Today, "it seems that even if there is baseline resistance or some poor prognostic indicators, the multiple targeting works to eradicate the virus and overcome the barriers."
As the new regimens work their way through the clinical trials process, he said, he and other doctors are trying to delay treatment "unless it is absolutely necessary."
But he cautioned that so far the "novel paradigms" are still being tested. "We're still waiting for the phase III trials and larger numbers," Kim said.
The study so far includes 66 patients in four treatment arms differing by the length of therapy and the dose of BMS-791325, Rodriguez-Torres reported.
The primary endpoint is the so-called SVR12 – viral levels too low to be quantified 12 weeks after the end of treatment.
Outcomes appeared similar regardless of the doses and length of treatment, Rodriguez-Torres reported -- in three arms, 94% of patients (or 15 out of 16) reached the primary endpoint.
In the fourth arm -- with 12 weeks of treatment and a higher dose of BMS-791325 -- 16 of 18 patients (89%) reached SVR12. One patient had viral breakthrough while on therapy and another relapsed during follow-up, she said.
Investigators saw only one serious adverse event -- a case of renal calculus that was judged not to be related to the study drugs, she reported.
There were no adverse events that led to patients stopping treatment and only one clinical adverse event that reached grade 3 or 4 -- a headache that resolved as treatment continued.
Investigators did not see any grade 3 or 4 laboratory abnormalities, Rodriguez-Torres said.
Follow-up is continuing and the study is being expanded to include other patient populations, Rodriguez-Torres said, adding: "We call it the study that never ends."
The study was supported by Bristol-Myers Squibb. Rodriguez-Torres reported financial links with the company and several authors are employees of BMS.
Primary source: IDWeek
Source reference: Rodriguez-Torres M, et al "Interim analysis of an interferon (IFN)- And ribavirin (RBV)-free regimen of daclatasvir (DCV), asunaprevir (ASV), and BMS-791325 in treatment-naive, hepatitis C virus genotype 1-infected patients" IDWeek 2013; Abstract 1828.
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