FDA Update

March 2014, Vol 4, No 2 - FDA Approvals, News & Updates


First Drug Combination Approved for Unresectable or Metastatic Melanoma

The US Food and Drug Admin­istration (FDA) approved the use of dabrafenib (Tafinlar; GlaxoSmith­Kline) plus trametinib (Mekinist; GlaxoSmithKline) as a new combination therapy for the treatment of patients with advanced melanoma that is unresectable or metastatic. The 2 drugs were individually approved by the FDA in 2013 for melanoma. Da­brafenib was initially approved for patients with melanoma whose tumors express the BRAF V600E mutation. The dabrafenibtrametinib combination is indicated for patients with melanoma who also have the BRAF V600E or BRAF V600K mutation. Approx­imately 50% of skin melanomas have a BRAF mutation.

The FDA approval was based on results of a clinical trial of 162 patients with unresectable or metastatic melanoma with the BRAF V600E or BRAF V600K mutation; the majority of the patients were treatment-naïve. They received dabrafenib as a single agent until their disease progressed or their side effects became intolerable, at which point they began using the combination. Overall, 76% of pa­tients receiving the combination had an objective response for an average of 10.5 months compared with 54% of patients receiving dabrafenib alone who had an objective response lasting 5.6 months. Clinical trials are ongoing to determine whether this combination will also result in improved survival.

The FDA approved this combination under its accelerated program, and also reviewed it under its priority review. (January 8, 2014)


Ibrutinib Approved for Chronic Lymphocytic Leukemia

The FDA approved a new indi­cation for ibrutinib (Imbruvica; Pharmacyclics) for the treatment of patients with chronic lymphocytic leukemia (CLL) who have received at least 1 previous therapy. The ap­proval was granted under the FDA’s accelerated approval process to expedite access to patients with CLL to this promising new medication.

In November 2013, the FDA granted accelerated approval to ibrutinib for the treatment of patients with mantle-cell lymphoma, a rare and aggressive type of hematologic cancer; this approval, too, was for patients who had received at least 1 previous therapy.

The approval of ibrutinib for the treatment of patients with CLL was also done under the priority review process of the FDA, based on the demonstration of the drug to have a significant improvement on the safety or efficacy of patients with this serious condition. Ibrutinib also received an orphan drug designation by the FDA.

The new FDA indication for ibrutinib for CLL is based on the results of a clinical trial with 48 previously treated patients with CLL. Patients were diagnosed with CLL, on average, 6.7 years before enrolling in the study and had received 4 previous therapies. Patients received oral ibrutinib until disease progression or unacceptable toxicity. Overall re­sponse was seen in nearly 58% of the patients, with a response duration of 5.6 months to 24.2 months during the study. (February 12, 2014)