Boceprevir, Interferon Alfa-2a, Ribavirin Effective in HCV

Neil Canavan

March 30, 2012

March 30, 2012 (New York, New York) — Peginterferon alfa-2a, in combination with the protease inhibitor boceprevir and ribavirin (R), was shown to have efficacy equivalent or superior to that seen with historical use of the same regimen with peginterferon alfa-2a — the standard of care — for treating hepatitis C virus (HVC) infection, according to data reported here at the International Conference on Viral Hepatitis (ICVH) 2012.

These results provide a definitive rationale for the inclusion of the alfa-2a interferon variant in the treatment regimen, allowing for greater ease of administration by the patient infected with HCV.

"This is the first trial in which peginterferon alfa-2a was used as a backbone instead of alfa-2b," said study investigator John Howe, PhD, senior principal scientist, Merck & Co., Inc, Whitehouse, New Jersey.

In a previous study of the combination with alfa-2b, the RESPOND-2 (Retreatment with HCV Serine Protease Inhibitor Boceprevir and PegIntron/Rebetol 2) trial, patients who were previously nonresponders or had relapsed after treatment with ribavirin and interferon alfa-2b showed significant improvement in sustained viral response (SVR) with the addition of boceprevir (66% vs 21% for controls).

The current investigation was a double-blind, placebo-controlled study that randomly assigned 201 HCV genotype-1 relapsers and nonresponders in a 1:2 fashion to 1 of 2 treatment groups. Treatment group 1 received 4 weeks of peginterferon alfa-2a and ribavirin followed by 44 weeks of placebo plus ribavirin plus peginterferon alfa-2a (standard of care). Treatment group 2 received 4 weeks of ribavirin plus peginterferon alfa-2a followed by boceprevir plus ribavirin plus peginterferon alfa-2a for 44 weeks.

Therapy was discontinued in both treatment groups if HCV RNA was undetectable at week 12 (defined as HCV RNA level of 9.3 IU/mL).

Results showed a superior efficacy for the boceprevir combination; 64% of patients achieved an SVR as compared with 21% in the control group (P < .0001).

The rate of relapse with the protease inhibitor combination, 12%, was lower than that with the standard of care, 33% (P value not reported).

"These results are consistent with RESPOND-2," said Dr. Howe.

Reasons for a non-SRV outcome in the boceprevir/peginterferon alfa-2a/ribavirin treatment group for a total of 44 patients were as follows: viral breakthrough on treatment after initially being undetectable for 1 patient; incomplete virologic response for 4 patients; relapse after treatment for 11 patients; and nonresponse for the remaining 28 non-SVR patients (this figure includes patients who discontinued treatment for any reason).

Samples from 33 of 44 patients who received boceprevir/peginterferon alfa-2a/ribavirin who did not achieve SVR were subjected to sequence analysis of postbaseline resistance-associated variants (RAVs). This analysis revealed that 8 of the 33 patients had RAVs; the total included 1 patient with viral breakthrough, 3 patients who had incomplete responses, 2 patients who relapsed, and 2 nonresponders.

By resistance locus, overall RAV profiles were similar to those in all other studies in which peginterferon alfa-2b was used as part of an HCV treatment combination. "The resistance data collected in this trial are consistent with results reported in SPRINT-2 and RESPOND-2," said Dr. Howe.

Treatment Choices With HCV

"I believe that these two interferons [alfa-2a, alfa-2b] are similar," commented Ayse Aytaman, MD, chief of gastroenterology and hepatology, Veterans Affairs New York Harbor Health Care System, Brooklyn, New York. "But we use the alfa-2a more commonly because it's easier for the patient. It is a prepared syringe, you don't have to give weight-based dosing, and it comes in different dosages. It is much simpler. It's particularly good for patients who have trouble understanding instructions."

As for choosing between the 2 new protease inhibitors now at her disposal (boceprevir and telaprevir), "We are trying to learn how to deal with them," she said. "Yes, they are very potent, but they have a lot of side effects."

Before adding interferon on top of a protease inhibitor, Dr. Aytaman cautioned that there are some patients for whom the physician may want to wait for better pharmacologic options before treating.

"When I look at a patient who is 60 years old, I have to consider that I'm going to take a year out of this person's life with them coming to me weekly, or biweekly, injecting himself, being miserable with flu-like symptoms… Why?" Even if the patient has early-stage cirrhotic disease, Dr. Aytaman is willing to wait for an all-oral HCV treatment combination with fewer side effects.

If she has to choose between the protease inhibitors available now, side effect profile is one consideration; cost is another.

"There is a huge cost difference. Telaprevir, even though it's only [given] for 3 months, is much more expensive than boceprevir. If it wasn't for that, every hepatologist I know would go for telaprevir because it's so much simpler, with a much shorter duration of treatment."

"The reality is, I'm given a budget to treat patients. If I can treat more patients for fewer dollars, I will," said Dr. Aytaman, "That said, I do use both. Most of my patients get boceprevir, but for previous null responders, or if I'm anticipating significant anemia or cytopenia, I go for telaprevir."

Dr. Howe is an employee of Merck & Co. Dr. Aytaman has disclosed no relevant financial relationships, and her opinions are expressed as a physician, not as an employee of the US government.

International Conference on Viral Hepatitis (ICVH) 2012. Abstract # 79317. Presented March 26, 2012.


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