Roche Gets Priority Review from FDA for Co-Infection

Roche announced today that the FDA had granted "a six-month Priority Review Status to the supplemental new biologics license application (sBLA) for Roche's combination therapy of Pegasys(R) (peginterferon alfa-2a) in combination with Copegus(R) (ribavirin, USP) for the treatment of chronic hepatitis C in patients co-infected with HIV. Roche submitted this file with the FDA in August 2004."

Roche's application is based on promising data from APRICOT, a study of almost 900 people co-infected with hepatitis C and HIV. Results from APRICOT were originally presented at an HIV conference in February, and published in the New England Journal of Medicine this summer (see abstract).

The results of APRICOT were striking:

Overall, 40% of people taking Pegasys (pegylated interferon) and Copegus (ribavirin) achieved a sustained virologic response (SVR - an undetectable hepatitis C viral load six months after the end of treatment).

29% of people with hepatitis C genotype 1 acheived an SVR.

62% of people with hepatitis C genotype 2 or 3 achieved an SVR.

These results were significantly better than those seen with Pegasys alone, or standard interferon plus ribavirin. However, SVR rates are substantially lower than those seen in clinical trials of pegylated interferon and ribavirin in people infected solely with hepatitis C.

In an editorial commentary accompanying the publication of the APRICOT results and those of another co-infection study, Dr. Jean-Michael Pawlotsky writes:

Because of shared routes of transmission, approximately one third of patients infected with human immunodeficiency virus (HIV) are also infected with HCV. Coinfected patients receiving highly active antiretroviral therapy have been shown to have higher rates of HCV-related morbidity (i.e., accelerated progression to cirrhosis, end-stage liver disease, and hepatocellular carcinoma) and mortality than patients who are infected with HCV alone. Two studies reported in this issue of the Journal by Torriani and colleagues and Chung and colleagues show that a sustained virologic response can be achieved with pegylated interferon alfa and ribavirin therapy in a substantial proportion of coinfected patients. These results, together with the poor prognosis for HIV-positive patients with HCV infection, justify broad use of antiviral therapy in the treatment of coinfected patients. However, it is apparent from these two studies that infection is eradicated in a substantially higher proportion of patients with HCV alone than of coinfected patients. The lower rates of a sustained virologic response among coinfected patients could be at least partially explained by lower rates of adherence to therapy, poorer tolerance of pegylated interferon alfa and ribavirin, and drug–drug interactions that lead to more frequent discontinuation of treatment or reductions of doses. HIV-induced immune perturbations and direct HIV–HCV interactions in the cells infected by both viruses could also play a role, through mechanisms that remain largely unknown.

Now that we have some data to think about, here are the questions for co-infected people and their doctors:

- Who should be treated? How do we calculate the benefits of treatment against the risks of side effects?

- How can we increase the odds of success in people with genotype 1? Would longer periods of treatment (say, 18 months instead of 12 months) help improve the likelihood of achieving an SVR? What about higher doses of ribavirin -- APRICOT used a relatively low dose (800 mg/day) due to concerns about anemia, so would 1,000-1,200 mg/day be more effective but equally safe?

- How can we encourage HIV doctors to take on hepatitis C treatment for their co-infected patients? How can we develop and support effective models of interdisciplinary care, that address both HIV and hepatitis C, while also providing quality care for mental health and addictions? How do we build in appropriate education and support for co-infected people facing complicated treatment decisions?

- How do we ensure that companies developing new, potentially safer or more effective hepatitis C treatments get studied in people co-infected with HIV in a timely fashion?

In the meantime, let's hope that Roche's filing for co-infection helps bring attention to this issue, and encourages more co-infected people (and their healthcare providers) to learn about hepatitis C treatment options.

More a thorough review of research hepatitis C treatment in people co-infected with HIV, see this chapter by Tracy Swan from TAG's Hepatitis C and HIV/HCV Coinfection Report.

Comments

[Susan R]

I think the health department ought to planning to control, monitor and regularize this process.

[Susan R]

I think the health department ought to planning to control, monitor and regularize this process.