Summer FDA Updates

Jason M. Broderick;

Summer FDA Updates

March 4, 2011

Jason M. Broderick

Publication

Article

Contemporary Oncology®Summer 2010

Volume 2

Issue 2

FDA updates from the summer of 2010

The FDA’s Oncologic Drugs Advisory Committee (ODAC) voted 12 to 1 against maintaining bevacizumab’s (Avastin’s) approval for treatment of breast cancer. The decision follows the FDA’s submission of a report to ODAC suggesting bevacizumab is not as effective in breast cancer as previous studies had indicated and is associated with more serious side effects than similar treatments. Although the FDA will most likely revoke bevacizumab’s breast cancer indication, the agency has overruled ODAC recommendations in the past. In 2008, the FDA’s initial approval of bevacizumab for breast cancer came despite ODAC’s 5 to 4 vote against it. Bevacizumab even received accelerated approval, with full approval predicated on positive data from the two additional studies being conducted by Genentech, the drug’s maker; however, as ODAC’s vote indicates, data from those studies showed that overall survival and tumor shrinkage are not as great as earlier studies demonstrated. The FDA’s decision will not affect bevacizumab’s other approved indications.
Abbott Laboratories received FDA clearance for its ARCHITECT HE4 (human epididymis protein 4) chemiluminescent microparticle immunoassay, which helps monitor recurrence and progression of ovarian cancer. HE4 is overexpressed by some patients with ovarian cancer, and a recent study by Hellstrom et al found it had the highest sensitivity and specificity among ovarian cancer biomarkers. CA125, the biomarker commonly used to track recurrence or progression, is not expressed in 20% of ovarian cancer cases. Research also indicates HE4 can improve earlystage ovarian cancer detection, which would improve survival rates.
The FDA has agreed to conduct a priority review of denosumab (Prolia) for the treatment of cancer-related bone damage. Denosumab, which has a different mechanism of action from currently approved bisphosphonates, was approved last year as a treatment for postmenopausal women at risk of osteoporosis. Amgen, the manufacturer of denosumab, said a decision is expected by November 18.
Perifosine, an experimental drug by Keryx, was granted orphan drug status by the FDA in neuroblastoma after positive data on its safety and efficacy from a phase I trial. Only 650 new cases of neuroblastoma are reported each year, and there are no approved treatments specifically for this cancer. Perifosine, an Akt inhibitor, already has an orphan-drug designation for multiple myeloma and refractory advanced colorectal cancer. Phase III trials are ongoing for perifosine in these malignancies.
The FDA is reviewing the safety of gonadotropin-releasing hormone (GnRH) agonists, testosterone-suppressing medications primarily used to treat prostate cancer. Ongoing analyses have connected GnRHs to increased risk of diabetes, heart attack, stroke, and sudden death. While the FDA does not recommend stopping GnRH use, it wants clinicians and patients to be aware of the potential side effects. The agency recommends close monitoring of patients at risk for cardiovascular disease and diabetes who are receiving androgen-deprivation therapy with Eligard, Lupron, Synarel, Trelstar, Vantas, Viadur, or Zoladex.
The FDA has approved two generic formulations of anastrozole, sold as Arimidex by AstraZeneca. Israelbased Teva Pharmaceutical and the West Virginia company Mylan Inc. will each be selling a generic version of the hormonal therapy, approved as an adjuvant therapy in postmenopausal women with breast cancer.
The FDA is holding hearings to discuss regulation of genetic tests used to diagnose disease. The agency is particularly concerned about tests marketed directly to consumers. The FDA has already warned companies selling genetic screening tests and tests designed to predict drug response to consumers that the kits appear to be medical devices and therefore require the agency’s approval. The FDA is also considering subjecting laboratory-developed tests that predict the risk of cancer recurrence to an approval process. The American Clinical Laboratory Association said it is concerned applying medical-device regulations to laboratory tests might hinder development.