FDA APPROVES EXPANDED USE OF IMBRUVICA TO TREAT CHRONIC LYMPHOCYTIC LEUKEMIA

FROM:  FOOD AND DRUG ADMINISTRATION 
FDA NEWS RELEASE
For Immediate Release: Feb. 12, 2014
FDA approves Imbruvica to treat chronic lymphocytic leukemia

The U.S. Food and Drug Administration today expanded the approved use of Imbruvica (ibrutinib) for chronic lymphocytic leukemia (CLL) patients who have received at least one previous therapy.

CLL is a rare blood and bone marrow disease that usually gets worse slowly over time, causing a gradual increase in white blood cells called B lymphocytes, or B cells. The National Cancer Institute estimates that 15,680 Americans were diagnosed and 4,580 died from the disease in 2013.

Imbruvica works by blocking the enzyme that allows cancer cells to grow and divide. In November 2013, the FDA granted Imbruvica accelerated approval to treat patients with mantle cell lymphoma, a rare and aggressive type of blood cancer, if those patients received at least one prior therapy.

“Today’s approval provides an important new treatment option for CLL patients whose cancer has progressed despite having undergone previous therapy,” said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “The FDA completed its review of Imbruvica’s new indication under the agency’s accelerated approval process, which played a vital role in rapidly making this new therapy available to those who need it most.”

Under the agency’s accelerated approval process, the FDA may approve a drug based on a surrogate or intermediate endpoint that is reasonably likely to predict clinical benefit. Drugs receiving accelerated approval are usually subject to an agreement to conduct confirmatory trials verifying and describing clinical benefit. Imbruvica for CLL also received priority review and orphan-product designation because the drug demonstrated the potential to be a significant improvement in safety or effectiveness in the treatment of a serious condition and is intended to treat a rare disease, respectively.

The FDA’s accelerated approval of Imbruvica for CLL is based on a clinical study of 48 previously treated participants. On average, participants were diagnosed with CLL 6.7 years prior to the study and had received four previous therapies. All study participants received a 420 milligram orally administered dose of Imbruvica until the treatment reached unacceptable toxicity or the disease progressed. Results showed nearly 58 percent of participants had their cancer shrink after treatment (overall response rate). At the time of the study, the duration of response ranged from 5.6 to 24.2 months. An improvement in survival or disease-related symptoms has not been established.

The most common side effects observed in the clinical study include low levels of platelets in the blood (thrombocytopenia), diarrhea, bruising, a decrease in infection-fighting white blood cells (neutropenia), low red blood cells (anemia), upper respiratory tract infection, fatigue, pain in the muscles and bones (musculoskeletal pain), rash, fever (pyrexia), constipation, swelling of tissues (peripheral edema), joint pain (arthralgia), nausea, mouth sores (stomatitis), sinus infection (sinusitis) and dizziness.

Imbruvica is manufactured by Sunnyvale, Calif.-based Pharmacyclics.

FDA APPROVES GAZYVA FOR TREATING CHRONIC LYMPHOCYTIC LEUKEMIA

FROM:  U.S. FOOD AND DRUG ADMINISTRATION 
FDA approves Gazyva for chronic lymphocytic leukemia
Drug is first with breakthrough therapy designation to receive FDA approval

The U.S. Food and Drug Administration today approved Gazyva (obinutuzumab) for use in combination with chlorambucil to treat patients with previously untreated chronic lymphocytic leukemia (CLL).

CLL is a blood and bone marrow disease that usually gets worse slowly. According to the National Cancer Institute, 15,680 Americans will be diagnosed and 4,580 will die from the disease this year.

Gazyva works by helping certain cells in the immune system attack cancer cells. Gazyva is intended to be used with chlorambucil, another drug used to treat patients with CLL.

Gazyva is the first drug with breakthrough therapy designation to receive FDA approval. This designation was requested by the sponsor and granted soon after the biologic license application to support marketing approval was submitted to the FDA. The FDA can designate a drug a breakthrough therapy at the request of the sponsor if preliminary clinical evidence indicates the drug may offer a substantial improvement over available therapies for patients with serious or life-threatening diseases.

The FDA also granted Gazyva priority review because the drug demonstrated the potential to be a significant improvement in safety or effectiveness in the treatment of a serious condition. And the FDA granted Gazyva orphan product designation because it is intended to treat a rare disease.

“Today’s approval represents an important new addition to the treatments for patients with CLL,” said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “This approval reflects the promise of the Breakthrough Therapy Designation program, allowing us to work collaboratively with companies to expedite the development, review and availability of important new drugs.”

Gazyva’s approval for CLL is based on a study of 356 participants in a randomized open-label multicenter trial comparing Gazyva in combination with chlorambucil to chlorambucil alone in participants with previously untreated CLL. Participants receiving Gazyva in combination with chlorambucil demonstrated a significant improvement in progression free survival: an average of 23 months compared with 11.1 months with chlorambucil alone.

The most common side effects observed in participants receiving Gazyva in combination with chlorambucil were infusion-related reactions, a decrease in infection-fighting white blood cells (neutropenia), a low level of platelets in the blood (thrombocytopenia), low red blood cells (anemia), pain in the muscles and bones (musculoskeletal pain), and fever (pyrexia).

Gazyva is being approved with a boxed warning regarding Hepatitis B virus reactivation and a rare disorder that damages the material that covers and protects nerves in the white matter of the brain (progressive multifocal leukoencephalopathy). These are known risks with other monoclonal antibodies in this class and rare cases were identified in participants on other trials of Gazyva. Patients should be advised of these risks and assessed for Hepatitis B virus and reactivation risk.

Gazyva is marketed by Genentech, a member of the Roche Group, based in South San Francisco, Calif.