New HCV Drugs May Be Worth the Wait

SAN FRANCISCO — Because new medications for hepatitis C are expected to be approved within 2 years, some experts are waiting to treat selected patients.

“Over the last year, I've moved increasingly toward deferred treatment, which is a change for me,” Dr. Norah A. Terrault said. “We clearly will have drugs that are going to work better” when used with the current standard regimen of pegylated interferon (peg-IFN) and ribavirin, she said at a meeting on HIV management sponsored by the University of California, San Francisco.

Approval is anticipated in 2011 for two protease inhibitors—telaprevir and boceprevir—that have been in phase III clinical trials for the treatment of hepatitis C virus (HCV), said Dr. Terrault, director of the Viral Hepatitis Center at the university. Using either of these drugs as add-on therapy with peg-IFN plus ribavirin should “push our sustained viral response rates up over 50% consistently,” she said. (See box.)

Clinicians should weigh the pros and cons of immediately treating HCV in patients who are coinfected with HIV, Dr. Terrault suggested. Coinfected patients tend to have accelerated progression of HCV disease with more liver-associated morbidity and mortality, compared with patients who have HCV but not HIV. Treating HCV in coinfected patients may improve the patient's ability to take highly active antiretroviral therapy to combat HIV.

On the other hand, patient characteristics or comorbidities may make it nearly impossible for some patients to tolerate the toxicities associated with peg-IFN and ribavirin. In general, coinfected patients tolerate HCV therapy less well than monoinfected patients. Interactions between HCV drugs and antiretrovirals may necessitate a change in HIV therapy. Clinicians must be comfortable with helping patients get through HCV therapy for it to succeed, Dr. Terrault said.

The main reason to consider deferring HCV therapy, however, is that “better treatments are, I think, just around the corner,” she said.

All of the new HCV treatments in the pipeline are being developed primarily for genotype 1 HCV, so Dr. Terrault does not defer HCV therapy for coinfected patients with genotypes 2 or 3 HCV. Patients with low levels of HCV RNA (less than 600,000 IU/mL) are most likely to achieve a sustained viral response to HCV therapy regardless of genotype, so she still offers HCV therapy to this group. She also offers HCV treatment to patients with advanced fibrosis (bridging fibrosis or cirrhosis) because “they can't wait for new treatments,” she said.

Dr. Terrault also treats acute HCV in coinfected patients who are on stable antiretroviral therapy with no active opportunistic infections and CD4 counts over 200 cells/mm

Disclosures: Dr. Terrault has been a consultant to Schering-Plough Corp., which is developing boceprevir, and to three other companies. She has received grants from Vertex Pharmaceuticals Inc., which is developing telaprevir, and from two other companies.

Therapies in The Pipeline

New treatments for HCV are being developed in several drug classes.

Preliminary data from phase III clinical trials of the two new treatments closest to market entry—the protease inhibitors telaprevir and boceprevir—suggest improved response rates and added toxicities when used with peg-IFN and ribavirin.

Based on early results with telaprevir, she anticipates that 69% of treatment-naive patients will achieve a sustained viral response to treatment with 12 weeks of triple therapy (telaprevir, peg-IFN, and ribavirin) followed by 12-36 weeks of peg-IFN and ribavirin. This regimen could produce response rates of up to 39% in patients who had not responded to previous treatment with peg-IFN and ribavirin, and up to 76% in patients who had relapsed from previous therapy with peg-IFN and ribavirin.

The boceprevir treatment regimen starts with 4 weeks of peg-IFN and ribavirin followed by 24-44 weeks of triple therapy by adding boceprevir. Dr. Terrault anticipates a sustained viral response at 48 weeks in up to 74% of previously untreated patients with genotype 1 HCV and no HIV. No data are available on the use of boceprevir in treatment-experienced patients.

“This is add-on treatment, so you still have peg-interferon and ribavirin side effects, and now you have protease inhibitor side effects,” she noted. Telaprevir most commonly causes anemia, rash, or pruritus. Boceprevir most commonly causes anemia, neutropenia, or dysgeusia.