By Michael Smith, North American Correspondent, MedPage Today
Published: April 25, 2013
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco
AMSTERDAM – An investigational protease inhibitor (PI) led to viral cures in about four out of five hepatitis C virus (HCV) patients, a researcher reported here.
In a phase III study, either of two doses of faldaprevir combined with pegylated interferon and ribavirin significantly outperformed placebo, according to Peter Ferenci, MD, of the Medical University of Vienna.
But importantly, Ferenci told MedPage Today during the meeting of the European Association for the Study of the Liver, they did so without the side effects associated with earlier drugs in the class.
The efficacy results are "indeed very good," commented Mark Thursz, MD, of St. Mary's Hospital in London, who was not involved in the study but who moderated a press conference at which some details were discussed.
But the most important aspect of the results, Thursz said, is the safety profile of the drug. "This will be far better tolerated by our patients in the clinic than the earlier PIs," he told reporters.
Two protease inhibitors – telaprevir (Incivek) and boceprevir (Victrelis) – have been approved for patients with the difficult-to-treat HCV genotype 1, but they have been associated with serious and sometimes dangerous adverse events.
Both, for instance, cause significant anemia, and telaprevir has been associated with life-threatening rash that in at least two cases led to death.
But they are the only drugs so far approved that directly target HCV; the companion medications, pegylated interferon and ribavirin, are respectively an immune booster and a viral replication inhibitor.
That was the context when the industry-sponsored trial was designed, Ferenci told MedPage Today – the earlier protease inhibitors were regarded as the competitors, with interferon (given intravenously) and ribavirin alone as the standard of care.
Since then, he said, there has been a "revolution" in HCV, with a host of oral direct-acting agents under investigation and clinicians hoping that interferon and perhaps ribavirin can be banished from the clinic.
Indeed, Ferenci noted, research is underway to see if faldaprevir, in combination with other oral direct-acting HCV drugs, can be effective in the absence of interferon and possibly without interferon or ribavirin.
In the current study, investigators enrolled 652 patients with genotype 1 HCV and randomly assigned them for 24 weeks to get placebo or either 120 or 240 milligrams of faldaprevir daily. All patients also got then-standard therapy with interferon and ribavirin.
Patients with what the investigators called "early treatment success" – defined as low levels of HCV at week 4 and undetectable levels at week 8 – were eligible to stop treatment at week 24, while others got another 24 weeks of interferon and ribavirin.
In the placebo arm, 22% of patients had early treatment success, Ferenci reported, compared with 87% in the low-dose faldaprevir arm and 89% in the high-dose arm, and stopped treatment at 24 weeks.
The primary endpoint of the study was 12-week sustained virologic response (SVR12) – no detectable HCV RNA 12 weeks after the end of treatment.
The investigators found that 52% of patients in the placebo arm reached that endpoint, similar to historical results. In the low-dose faldaprevir arm, the SVR12 rate was 79%, compared with 80% in the high-dose arm (P<0.0001 for both).
The only adverse event clearly caused by the drug, Ferenci said, was an elevation in bilirubin, but that was not associated with elevated liver enzymes and had "no clinical significance."
Some patients reported rash but did not need medical attention for it, he added.
Indeed, he said, the rates of most observed adverse events, including those regarded as serious, were similar among the arms, with little difference in discontinuations owing to adverse events.
The study was supported by Boehringer Ingelheim. Ferenci reported financial links with the company and with Roche, Merck, Vertex, Idenix, Achelion, Rottapharm-Madaus, and BMS.
Thursz reported financial links with Abbott and Gilead.
Primary source: European Association for the Study of the Liver
Source reference:
Ferenci P, et al "Faldaprevir plus pegylated interferon alfa-2A and ribavirin in chronic HCV genotype-1 treatment-naïve patients: final results from STARTVERSO1, a randomised, double-blind, placebo controlled phase III trial" EASL 2013; Abstract 1416
No comments:
Post a Comment