HCV Polymerase Inhibitor R-1626 Advances to Phase II Study

By Ronald Baker, PhD

The U.S. Food and Drug Administration (FDA) has granted “fast track” review status to R-1626, a new oral polymerase inhibitor for the treatment of hepatitis C, according to an announcement from Roche Laboratories. The FDA “fast track” designation facilitates development and expedites the review of promising drugs for serious or life-threatening illnesses such as chronic hepatitis C virus (HCV) and HIV infection.

Shown in an earlier study to have a strong antiviral effect against HCV, R-1626 is now entering Phase II development. The Phase II trial will evaluate the safety and antiviral effects of R-1626 in combination with the current standard of care for hepatitis C, peginterferon plus ribavirin combination therapy.

R-1626 has a different mechanism of action compared with current standard HCV therapies. In a Phase I study, the drug produced significant reductions in HCV viral load in chronic hepatitis C patients infected with genotype 1, the most difficult form of the virus to treat. Patients with HCV genotype 1 in clinical trials with pegylated interferon alfa-2a (Pegasys) plus ribavirin have approximately a 50% chance of achieving a cure, defined as a sustained virological response (SVR) to therapy (undetectable HCV RNA 6 months after the completion of treatment). While this SVR rate represents an improvement over treatment with conventional (non-pegylated) interferon plus ribavirin or pegylated interferon monotherapy, there is a pressing need for new treatments that improve SVR rates and cause fewer adverse side effects.

The Phase II study of R-1626 suggests that Roche is committed to improving therapeutic options for patients with hepatitis C.

“New medicines such as R-1626 have strong antiviral activity and the potential to help more patients achieve treatment success, especially when used in combination with current treatments,” said Dr. Paul Pockros, head of the Division of Gastroenterology and Hepatology at the Scripps Clinic in San Diego and principle investigator of the study. “A product that could potentially improve treatment success rates, particularly for the hardest-to-treat forms of the virus, is much needed.”

The ongoing multicenter Phase II trial is enrolling patients in the U.S. with genotype 1 chronic hepatitis C who have not previously received treatment. The objectives of the study are to evaluate the 4-week safety and antiviral effect of R-1626 plus Pegasys and/or ribavirin.

Patients will be randomized into 4 treatment groups:

Group A: R-1626 1500 mg twice daily + 180 mcg Pegasys as a subcutaneous injection every week for 4 weeks;

Group B: R-1626 3000 mg twice daily + 180 mcg Pegasys every week for 4 weeks;

Group C: R-1626 1500 mg twice daily + 180 mcg Pegasys every week + ribavirin 1000-1200 mg daily for 4 weeks;

Group D: 180 mcg Pegasys + ribavirin 1000-1200 mg daily (standard of care group) for 4 weeks.

Following the first 4 weeks of treatment, all patients will receive 180 mcg Pegasys every week with ribavirin 1000-1200 mg daily for another 44 weeks, for a total treatment duration of 48 weeks.

About Fast Track Status

The criteria under which FDA grants “fast track” status require that the product's indication represents a serious or life-threatening condition, and the product has the potential to meet an unmet medical need. This designation allows for increased communication between the sponsor and the FDA during the product’s development and enables a “rolling submission,” which means Roche may submit reviewable portions of the New Drug Application (NDA) before submitting the complete NDA in order to facilitate the review process for R-1626.

“We are delighted to be granted fast track designation from the FDA,” said Nick Cammack, Roche’s director of Viral Diseases Research. “The development of R-1626, along with our extensive partnerships with other companies and our ongoing research with Pegasys, underscores our long-term commitment to improving outcomes for patients living with chronic hepatitis C.”

About Hepatitis C

Hepatitis C, a blood-borne infectious disease of the liver, is transmitted through body fluids, primarily blood or blood products, and by sharing needles. Hepatitis C chronically infects an estimated 2.7 million Americans and 170 million people worldwide and is the leading cause of cirrhosis and liver cancer and the number one reason for liver transplants in the U.S.

Link to Hepatitis C Section of HIV and Hepatitis.com

Important Safety Information about Pegasys

What is Pegasys?

Pegasys is a medicine used to treat some adults who have hepatitis C or hepatitis B and signs of liver damage. Pegasys works to reduce the amount of virus in your blood, helping your body fight the virus. Pegasys (Peginterferon alfa-2a), like other alpha interferons, can cause fatal or make life-threatening problems worse (like mental, immune system, heart, liver, lung, intestinal and infections). Your doctor should monitor you during regular visits. If you show signs or symptoms of these conditions, your doctor may stop your medication. In most patients, these conditions get better after you stop taking Pegasys (see medication guide for more information and warnings).

What is Copegus?

Copegus is a medicine that works by slowing down the growth of the virus. Copegus should be taken with Pegasys to fight the virus. Do not take Copegus by itself. Copegus (ribavirin, USP) can be extremely harmful and cause birth defects in an unborn baby. Female patients and the female partners of male patients should avoid getting pregnant. Ribavirin is known to cause anemia (low red blood cells), which can make heart disease worse. Also, ribavirin can harm your DNA and possibly cause cancer (see medication guide for more information and warnings).

Who should not take Pegasys and Copegus?

Do not take Pegasys alone or with Copegus if:

You are pregnant or your partner is pregnant

You or your partner plan to get pregnant during therapy or within 6 months after treatment ends

You are breastfeeding

You have hepatitis caused by your immune system (autoimmune hepatitis)

You have unstable or severe liver disease before or during treatment

You are allergic to alpha interferons or any of the ingredients in Pegasys and Copegus

You have abnormal red blood cells (caused by conditions like sickle-cell anemia or thalassemia major)

What if I am pregnant or thinking about having a baby?

If you are a woman who could get pregnant, you must take pregnancy tests before, during and for 6 months after treatment ends to make sure you are not pregnant.

During treatment and for 6 months after treatment, female and male patients must:

Use two forms of birth control (one being a condom with spermicide)

Tell your doctor right away if you or your partner becomes pregnant. You or your doctor should also call the Ribavirin Pregnancy Registry at 1-800-593-2214

What medication should I avoid when I am taking Pegasys and Copegus?

You should not take didanosine (ddI; Videx) with Copegus. Talk to your doctor about all medications that you are taking.

What are the possible side effects?

The most common side effects of Pegasys and Copegus are:

Flu-like symptoms (including fever, chills, muscle aches, joint pain, headaches)

Tiredness

Upset stomach (like nausea, taste changes, diarrhea)

Blood sugar problems (may lead to diabetes)

Skin problems (like rash, dry or itchy skin, redness and swelling at injection site)

Hair loss (temporary)

Trouble sleeping

The most serious side effects of Pegasys and Copegus are:

Risks to pregnancies

Mental health problems (such as irritability, depression, anxiety, aggressiveness, trouble with drug addiction or overdose, thoughts about suicide, suicide attempts, suicide and thoughts about homicide)

Blood problems (like a drop in blood cells leading to increased risk for infections, bleeding and/or heart or circulatory problems)

Infections (which sometimes cause death)

Lung problems (like trouble breathing, pneumonia)

Eye problems (like blurred vision, loss of vision)

Autoimmune problems (such as psoriasis, thyroid problems)

Heart problems (including chest pain and, rarely, a heart attack)

Liver problems (rarely, liver function worsens). Patients with both the hepatitis C virus and HIV can have an increased chance of having liver failure during Pegasys treatment. Change in a blood test that measures liver inflammation occurs more often in patients with hepatitis B. If you have a rise in this blood test you may need to be watched more closely with additional blood tests.

Tell your doctor immediately if you think you or your partner may be pregnant or if any of these symptoms occur.

More Information on Pegasys and Copegus on HIV and Hepatitis.com

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10/17/06

Source
Roche Laboratories.

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