FDA Update

FDA Approves First Drug Developed for Children with Rare Brain Tumor

Last week, the U.S. Food and Drug Administration approved Afinitor Disperz—pediatric doses of everolimus (Afinitor) tablets—to treat a rare brain tumor called subependymal giant cell astrocytoma (SEGA). Afinitor Disperz is the first approved form and dose of a drug developed to treat pediatric tumors.

Afinitor Disperz dissolves easily in a small amount of water, making the treatment easy to administer to patients who are unable to swallow whole tablets. It is also available in smaller doses than everolimus, the adult form of the drug.

Afinitor Disperz is recommended to treat patients 1 year of age and older who have tuberous sclerosis complex (TSC) and are diagnosed with SEGA but who are ineligible for surgery. Prior to the approval of this new dosage form, everolimus was recommended only for patients 3 years of age and older.

TSC is a rare genetic disease that causes tumors to grow in the brain and other vital organs. SEGA is a slow-growing tumor that can cause life-threatening complications by blocking the flow of fluid in the brain. These tumors occur in 6 to 9 percent of TSC patients, generally children and young adults.

Everolimus blocks the uncontrolled activity of a protein called mTOR kinase, which plays a critical role in the development and growth of SEGA tumors occurring in patients with TSC.

Everolimus was granted accelerated approval in 2010 to treat SEGA in patients with TSC.
Everolimus and Afinitor Disperz remain under accelerated approval for the treatment of SEGA in patients with TSC. Everolimus’ manufacturer, Novartis, updated safety and efficacy data from the single-arm study of 28 pediatric and adult patients used to support the drug’s accelerated approval in 2010 for the treatment of SEGA in patients with TSC.

In a more recent study involving 117 pediatric and adult patients who were randomly assigned to take everolimus or a placebo daily, 35 percent of patients treated with everolimus experienced tumor shrinkage compared with none who were treated with placebo. The most common side effects observed in patients with SEGA were mouth ulcers and respiratory tract infections.

Studies continue to evaluate the long-term safety and effectiveness of everolimus and Afinitor Disperz in pediatric and adult patients with SEGA. Afinitor Disperz is classified as an orphan drug because it is intended to treat a rare disease or condition. Afinitor Disperz’s application was granted priority review, which the FDA completed in 6 months.

New Treatment for Severe Neutropenia Approved

The U.S. Food and Drug Administration approved a drug called tbo-filgrastim to shorten bouts of severe neutropenia, a condition that leads to decreased levels of infection-fighting white blood cells (neutrophils). Some patients with cancer who receive chemotherapy develop severe neutropenia.

Tbo-filgrastim is intended for adults who have cancers other than blood or bone marrow cancers and who are taking chemotherapy drugs that substantially decrease the production of neutrophils in the bone marrow. This reduction in neutrophils may lead to infection and fever (febrile neutropenia).

Injections of tbo-filgrastim stimulate the bone marrow to increase the production of neutrophils and are administered 24 hours after chemotherapy treatment.

A randomized clinical trial showed that patients treated with tbo-filgrastim recovered from severe neutropenia in 1.1 days compared with 3.8 days for those who received the placebo. The study involved 348 patients with advanced breast cancer who were being treated with doxorubicin (Adriamycin) and docetaxel (Taxotere).

In three clinical trials evaluating the drug’s safety, the most common side effect observed was bone pain.

FDA Approves Drug to Treat Rare Type of Leukemia

Last month, the Food and Drug Administration (FDA) approved vincristine sulfate liposome (Marqibo) to treat adults with a rare disease called Philadelphia chromosome-negative acute lymphoblastic leukemia (ALL).

Vincristine sulfate liposome is approved for patients whose leukemia has returned at least twice or whose leukemia has progressed following two or more prior treatments. The drug contains vincristine, a common anticancer agent, encased within a liposome, a drug delivery vehicle composed of material similar to that of cell membranes. It is an injection administered once a week by a health care professional.

The drug’s effectiveness was evaluated in a clinical trial of adults whose leukemia had relapsed at least twice despite standard treatments and who had responded to at least one previous treatment for at least 90 days. Ten of the 65 enrolled patients (15.4 percent) had a complete remission or a complete remission with an incomplete blood count recovery. In these 10 patients, the remissions lasted for a median of 28 days. The median time to the first post-remission event (relapse, death, or next therapy) was 56 days.

The drug’s safety was evaluated in two single-arm trials that included 83 patients whose leukemia had relapsed at least twice. Serious adverse events, such as low white blood cell counts with fever, low blood pressure, respiratory distress, and cardiac arrest, occurred in 76 percent of the patients studied. The most common side effects included constipation, nausea, low blood cell counts, fever, nerve damage, fatigue, diarrhea, decreased appetite, and insomnia.

A warning that the drug must be administered intravenously because it is deadly if given in other ways, such as into the spinal fluid, will be included in the prescribing information. The warning also states that the dosage recommendations for vincristine sulfate liposome and vincristine sulfate are different. To avoid overdosing, health care professionals must verify the drug name and the dose before administration.

The drug was approved under the accelerated approval program, which allows the FDA to approve a drug based on clinical data showing that it is reasonably likely to provide a clinical benefit to patients. The manufacturer must conduct more clinical studies to confirm the drug’s benefit and safety. Vincristine sulfate liposome also received orphan-product designation because it is intended to treat a rare disease.