FDA News – May 2016

May 2016, Vol 7, No 4 - FDA Approvals, News & Updates


Cabometyx Receives FDA Approval for Advanced Renal-Cell Carcinoma

On April 25, 2016, the FDA approved cabozantinib (Cabometyx; Exelixis) tablets for the treatment of patients with advanced renal-cell carcinoma (RCC) who had received anti-angiogenic therapy. The FDA granted this approval under its fast track and priority review procedures. The approval was based on 1 randomized clinical trial of patients with advanced RCC who had previously received anti-angiogenic therapy and were randomized to oral cabozantinib 60 mg daily (N = 330) or to everolimus 10 mg orally once daily (N = 328). The primary end point was progression-free survival (PFS) in the first 375 randomized patients. The median PFS in this group was 7.4 months with cabozantinib and 3.8 months with everolimus (P <.001). The median overall survival in the full study population was 21.4 months and 16.5 months, respectively. The response rate was 17% versus 3%, respectively. The safety of cabozantinib was evaluated in 331 patients. The most common adverse reactions included diarrhea, fatigue, nausea, decreased appetite, palmar-plantar erythrodysesthesia syndrome, hypertension, vomiting, weight loss, and constipation. In addition, 60% of patients receiving cabozantinib had ≥1 dose reductions. Serious adverse events were reported in 40% of patients; these included abdominal pain, pleural effusion, diarrhea, and nausea. The recommended dose and schedule for cabozantinib is 60 mg orally daily. Cabozantinib received a breakthrough therapy designation from the FDA in August 2015

Venclexta First BCL-2 Targeted Drug Approved for Patients with CLL plus 17p Deletion

On April 11, 2016, the FDA approved the oral oncolytic venetoclax (Venclexta; AbbVie/Genentech) for the treatment of patients with chronic lymphocytic leukemia (CLL) associated with chromosome 17p deletion who had received at least 1 previous therapy. The FDA approved this indication under its priority review and accelerated approval processes, and also granted the drug an orphan drug status. Venetoclax is the first FDA-approved drug that targets the B-cell lymphoma (BCL)-2 protein. The overexpression of BCL-2 in CLL cells mediates tumor-cell survival and has been linked to resistance to chemotherapy. Venetoclax helps restore tumor-cell apoptosis by binding directly to the BCL-2 protein and triggering the activation of caspases. Patients with the 17p deletion lack a portion of the chromosome that helps to suppress cancer cell growth; this abnormality occurs in 10% of patients with untreated CLL and in 20% of patients with relapsed CLL. The approval was based on 1 single-arm clinical trial with 160 patients with CLL and the 17p deletion who had received ≥1 previous therapies; all patients received daily venetoclax treatment. Overall, 80% of the patients showed a complete or partial remission of their tumor. The median time to first response was 0.8 months, and the duration of response ranged from 2.9 months to >19 months. The most common adverse reactions were neutropenia, diarrhea, nausea, anemia, upper respiratory tract infection, thrombocytopenia, and fatigue. Serious events can include pneumonia, fever, autoimmune hemolytic anemia, and tumor lysis syndrome. Patients receiving venetoclax should not be using live attenuated vaccines. In January 2016, the FDA granted venetoclax a breakthrough therapy designation. Venetoclax was approved for use in patients with CLL whose 17p deletion status was confirmed by the companion diagnostic test called Vysis CLL FISH Probe Kit (manufactured by Abbott).  

First Blood Test for CRC Screening Approved by FDA

On April 13, 2016, the FDA approved Epi proColon (manufactured by Epigenomics), the first and only blood-based test for colorectal cancer (CRC) screening of people who are at average risk for CRC and who do not want to undergo screening with conventional (and guideline-recommended) methods with colonoscopy and/or fecal immuno­chemical test. This new, in vitro PCR blood test is a convenient screening option for CRC, but the FDA warns it is not appropriate for people at high risk for CRC. A positive test result requires follow-up testing with colonoscopy. The FDA warns that the blood test is not intended to replace CRC screening by colonoscopy. Furthermore, a negative test result does not guarantee lack of cancer, and positive results have been seen in patients with diagnosed lung cancer, chronic gastritis, and in pregnant women, according to the FDA. The company will conduct a postapproval study to confirm the long-term benefits of blood-based CRC screening with the Epi proColon test. The approval of Epi proColon was based on the results of 3 major clinical trials.  

Defitelio FDA Approved for Hepatic Veno-Occlusive Disease After HSCT

On March 30, 2016, the FDA approved defibrotide sodium (Defitelio; Jazz Pharmaceuticals) for the treatment of patients (adults or pediatric) with hepatic veno-occlusive disease (VOD) who have renal or pulmonary dysfunction after hematopoietic stem-cell transplantation (HSCT). The approval was granted using the FDA priority review. The approval was based on 3 studies with a total of 528 patients: 2 prospective clinical trials and 1 expanded-­access study. All patients had hepatic VOD with multiorgan dysfunction after HSCT. Patients received intravenous defibrotide sodium 6.25 mg/kg every 6 hours until VOD resolution. The primary end point was survival at day +100 after HSCT. The day +100 survival rates for the 3 studies were 38%, 44%, and 45% for Study 1, Study 2, and Study 3, respectively. The most common adverse reactions were hypotension, diarrhea, vomiting, nausea, and epistaxis. Defibrotide sodium is contraindicated in patients who are concurrently receiving anticoagulant treatment or fibrinolytic therapies. Hemorrhage and hypersensitivity reactions are the main risks associated with this drug. The recommended dose and schedule for defibrotide sodium is 6.25 mg/kg intravenously every 6 hours, given as a 2-hour infusion for at least 21 days, and continued until VOD resolution or up to 60 days of treatment.