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New meds offer hope for interferon-free regimen
by Larry Buhl

LifeGuide [Hep Talk]

Peter Piliero, MD
In the past year several protease inhibitors were introduced for chronic hepatitis C, marking a huge leap forward in treatment by providing, essentially, a cure for this disease.

Now, the emphasis is turning to ease-of-use issues and the elimination of older hepatitis C (HCV) meds.

For years pegylated interferon (peginterferon), along with ribavirin, has been the main therapy for chronic hepatitis C infection—and it has been the bane of patients and doctors alike, due to its sometimes severe side effects. Fever, nausea, fatigue and depression, along with other maladies, are too-common among patients on the regimen, and cause patients to say “why bother?” If the treatment is worse than the symptoms of the disease, they say—and often the symptoms of HCV are undetectable—then there’s no point to a lengthy, unpleasant regimen. Even breakthrough protease inhibitors like boceprevir and telaprevir are meant to be used with peginterferon for best results.

But HCV treatment research is moving fast, and there are next-generation meds in various stages of research that promise pill-only regimens for treating chronic hepatitis C.

Two antivirals
Results of a Phase IIb study by Boehringer Ingelheim on two HCV direct-acting antivirals was presented at the American Association for the Study of Liver Diseases (AASLD) conference in November. The study, SOUND-C2, showed that the combination of two oral direct-acting HCV compounds—the protease inhibitor BI 201335 and the polymerase inhibitor BI 207127, along with ribavirin—suppressed the hepatitis C virus to undetectable levels in the majority of patients. All patients in the five arms of the study were treatment-naïve and infected with genotype 1 HCV, the hardest-to-treat genotype. With the two oral antivirals plus ribavirin, more than three-quarters achieved a reduction in their viral load below the lower limit of quantifiable levels after twelve weeks.

Peter Piliero, MD, vice president, Clinical Development and Medical Affairs at Boehringer Ingelheim, tells A&U that the results are very encouraging and offer hope for difficult-to-treat populations with chronic hepatitis C.

“When I was treating patients it was great to have peginterferon at the time, but it was not popular with the patients. There is a great potential advance of oral, direct acting antivirals versus today’s therapy of a single oral plus peginterferon and ribavirin. By taking out peginterferon, you’ll not only eliminate or reduce many side effects of the regimen, you’ll help patients adhere to the regimen.”

Less than twelve percent of patients in the Phase IIb study dropped out due to side effects—including photosensitivity, nausea, jaundice, vomiting and diarrhea—which is “pretty reasonable” according to Piliero, and much lower than those who discontinue therapy with peginterferon.

Piliero notes that the study is ongoing and that Phase III is being planned and will be starting soon. “We must now complete the study to confirm if this interferon-free regimen leads to a sustained viral response.”

Second generation NSA inhibitor
While it is not as far along in the research process, a new direct-acting retroviral, ACH-3102, was nominated for inclusion in a clinical trial by Achillion Pharmaceuticals. What’s different about this drug is that it is an HCV NS5A inhibitor, a protein whose function is not fully understood but appears to play a role in viral replication and influence host response. ACH-3102 in preclinical studies has demonstrated potent pan-genotypic activity against HCV genotypes 1–6, including excellent activity against both the genotype 1a subtype and known mutant variants of genotype 1 HCV, according to Achillion.

“NS5A inhibitors, in combination with protease inhibitors, will play an integral role in achieving the goal of an all-oral once-daily direct acting antiviral regimen that possesses pan-genotypic activity against HCV,” commented Michael D. Kishbauch, president and CEO of Achillion, in a prepared statement. “The advancement of ACH-3102 toward clinical studies, combined with the trial results anticipated near year-end on our protease inhibitors, ACH-1625 and the pan-genotypic agent ACH-2684, and our first generation NS5A inhibitor, ACH-2928, position Achillion’s pipeline to deliver multiple potential combination possibilities for an interferon-free treatment for HCV.”

These and, inevitably, more upcoming meds, offer greater hope for hepatitis C patients, offering a cure without the pain.

Larry Buhl is a freelance journalist and screenwriter living in Los Angeles.

December 2011