REALIZE Gets Real

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Hep Talk

Hepatitis C Antiviral Telaprevir Moves Closer to Approval
by Larry Buhl

Researchers in a recent Phase III study are encouraged by the results of a new drug proposed to be used as part of combination therapy treatment for hepatitis C. In the study ending in September, the drug telaprevir resulted in a sustained viral response (SVR or viral cure) for sixty-five percent of people with a telaprevir-based regimen, as compared to seventeen percent of people in the control arm who received pegylated interferon and ribavirin alone.

Telaprevir and other direct-acting antivirals, or DAAs, involve an oral inhibitor of the hepatitis C virus protease, which is an enzyme required in order for the virus to reproduce. DAAs like telaprevir, when approved, are likely to remain part of a treatment regimen that includes HCV protease inhibitors to kill infected cells and protect new cells from hepatitis C by preventing HCV replication.

Vertex’s Phase III study, called REALIZE, enrolled three groups of patients with genotype 1 hepatitis C who had undergone at least one prior treatment course with pegylated interferon and ribavirin but did not achieve SVR. These patients had either relapsed, or achieved a partial response, or had almost no response. REALIZE is the only Phase III hepatitis C study to date of an investigational direct-acting antiviral therapy designed to evaluate all major
subgroups of people whose prior treatment was unsuccessful. The REALIZE study was conducted by Vertex’s collaborator, Tibotec.

Researchers consider the study a huge success. “The REALIZE data represent a major milestone in the development of new treatments for hepatitis C, as patients who received telaprevir-based therapy had a viral cure rate almost four times greater than the cure rate in those treated with available medicines,” said Robert Kauffman, MD, PhD, chief medical officer for Vertex.

With results from REALIZE and previous trials ILLUMINATE and ADVANCE, Vertex now has enough data required to complete their New Drug Application submission to the U.S. Food and Drug Administration. It is unclear how long the FDA will take to review the application, so the company would not speculate on when telaprevir might reach the market. A spokesperson for Vertex said the company would ask the FDA for accelerated approval, which usually takes about six months.

Preparing to educate doctors and patients
Vertex is already working on an education plan to help doctors and patient advocates understand the barriers and limitations patients may face when taking the medication, according to Dr. Camilla Graham, clinical assistant professor of medicine at Harvard Medical School, and part of the Vertex Medical Affairs team.

“Physicians must understand how management of hepatitis C is different with DAAs,” Graham told A&U. “Additionally, we are working with the investigators from the clinical trials that evaluated telaprevir and advocacy organizations to ensure that doctors are prepared for telaprevir.”
Graham, who is also a practicing physician at Beth Israel Deaconess Medical Center in Boston, points out that one of the pitfalls of using the drug is patient adherence.

“The hepatitis C population is a very diverse group of people and we have done extensive research, by talking with doctors and advocates, to understand the barriers and limitations patients may face regarding adherence,” she explained. “Adherence is not something that is new or different for telaprevir. It’s a universal issue and we are currently developing programs that would help patients stay adherent to the treatment regimen.”

DAAs that specifically target certain steps in the hepatitis C virus life cycle are in late-stage development. Even if telaprevir and other DAAs prove to be as successful as anticipated, pegylated interferon (also known as peginterferon) and ribavirin—the current standard of care for hepatitis C—will not go away.

Graham says that the new treatment regimen would likely be twelve weeks of telaprevir in combination with pegylated-interferon and ribavirin, followed by treatment with pegylated interferon and ribavirin alone for either twenty-four or forty-eight weeks of total treatment depending on the patient population and their response to treatment.

Vertex also has an ongoing Phase II trial in HIV/HCV coinfected patients. Information about the trial as well as information on other ongoing clinical trials for telaprevir can be found at www.clinicaltrials.gov.

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

October 2010