In fiscal year 2011, FDA approved 7 “new molecular entities” (NMEs) in oncology.
2. Zelboraf (vemurafenib) and companion genetic test for late-stage melanoma.
Importance: Zelboraf was the first drug in a new class of drugs to treat patients with late-stage (metastatic) or unresectable (cannot be removed by surgery) melanoma, the most dangerous type of skin cancer. Melanoma is the leading cause of death from skin disease. An estimated 68,130 new cases of melanoma were diagnosed in the
during 2010, and about 8,700 people died from the disease last year, according to the National Cancer Institute. 2011 was an important year for patients with late- stage melanoma. Zelboraf was the second new cancer drug (after Yervoy approved in March 2011) ever approved by FDA that demonstrated an improvement in overall survival. Zelboraf was also the first important approval of FY United States 2011 in the quest for targeted or “personalized” medicine, in this case allowing for the identification of patients most likely to respond to this drug therapy. Zelboraf is specifically indicated for the treatment of patients with melanoma whose tumors express a gene mutation called BRAF V600E. Zelboraf is being approved with a first-of-a-kind genetic test called the cobas 4800 BRAF V600 Mutation Test, a companion diagnostic that will help determine if a patient’s melanoma cells have the BRAF V600E mutation. This type of melanoma is an orphan disease.
Actions by FDA to speed drug testing and review. Zelboraf was given a Fast Track designation because it had the potential to improve overall survival in melanoma patients. Zelboraf’s safety and effectiveness were established in a single international trial of 675 patients with late-stage melanoma with the BRAF V600E mutation who had not received prior therapy. FDA did not require the sponsor to replicate the study findings in a second trial. Patients were assigned to receive either Zelboraf or dacarbazine, another anti-cancer therapy. The trial was designed to measure overall survival (the length of time between start of treatment and death of a patient). The median survival (the length of time a patient lives after treatment) of patients receiving Zelboraf has not been reached (77 percent still living) while the median survival for those who received dacarbazine was 8 months (64 percent still living). Because of convincing early findings with this drug, FDA scientists worked proactively with the sponsor during drug testing to encourage early submission of the application. FDA also encouraged the sponsor to open an expanded access protocol to permit patients earlier access to Zelboraf. Zelboraf was reviewed under the FDA’s priority review program which provides for an expedited six-month review of drugs.
Safety issues: About 24 percent of patients developed a skin-related cancer called cutaneous squamous cell carcinoma, which was managed with surgery. Other common side effects reported in patients receiving Zelboraf included joint pain, rash, hair loss, fatigue, nausea, itching, and skin sensitivity when exposed to the sun. FDA concluded that the benefits of Zytiga outweighed these risks.
Source: FDA - FY 2011 Innovative Drug Approvals