On Wed, Feb 8, 2012 the FDA Oncology Advisory Committee will discuss Amgen‘s supplement to their approved BLA for XGEVA (denosumab) for treatment of men with castrate-resistant prostate cancer at high risk of developing bone metastases.
This Advisory Committee discussion and the ultimate FDA approval decision comes down once again to the basic benefit risk decision. On the benefit side, treatment with denosumab did not result in an improvement in overall survival or progression free survival but it did improve bone metastasis-free survival (BMFS) and time to first bone metastasis, both by about 4 months. On the risk side, the incidence of osteonecrosis of the jaw with denosumab increased by about 5%. So, the basic benefit risk question is does the 4 month improvement outweigh the 5% increased risk?
The other significant question raised by the FDA appears to boil down to whether treatment with denosumab in this setting offers any advantage versus “prevention of skeletal related events in patients with solid tumors metastatic to bone”, the approved indication.
The FDA review appears to be on the negative side of neutral. While the company met the primary endpoint, the FDA review points out that at meetings with the company, the FDA noted that “overall survival, patterns of metastases, and the development of symptomatic metastases will be important review issues”. There was no advantage in overall survival. Also, of significant note is the statement in the FDA review that the study was not conducted under a Special Protocol Assessment, meaning there is no “contract” for approval just because the primary endpoint (improvement in BMFS) was met.
As promised earlier, we are providing a more detailed listing of upcoming FDA Advisory Committee Meetings.
Of particular interest, Vivus‘s QNEXA is scheduled to be reviewed on Feb 22, 2012 by the Endocrinologic and Metabolic Committee for weight management. Equally important, the FDA has scheduled another meeting of the Endocrinologic and Metabolic Committee for March 28-29, 2011. Could it be that we might hear some discussion on revised guidelines?
Jan 30-31, 2012 Pediatric Advisory Committee Meeting
- The Committee will discuss the status of the development of a number of drugs for pediatric use.
Feb 8-9, 2012 Oncologic Drugs Advisory Committee Meeting
The Committee will discuss:
- XGEVA (denosumab) by Amgen for castrate resistant prostate cancer.
- DACOGEN (decitabine) by Eisai for acute myelogenous leukemia.
- PIXUVRI (pixantrone dimaleate) by Cell Therapeutics for Non-Hodgekins Lymphoma
Feb 10, 2012 Cellular, Tissue and Gene Therapies Advisory Committee Meeting
- No products are currently on the schedule for review.
Feb 10, 2012 Neurological Devices Panel Advisory Committee Meeting
- No products are currently on the schedule for review
Feb 22, 2012 Endocrinologic and Metabolic Advisory Committee Meeting
- The committee will discus QNEXA by Vivus for weight management
Feb 23, 2012 Cardiovascular and Renal Drug Advisory Committee Meeting
- The committee will discuss NORTHERA by Chelsea Therapeutics for neurogenic orthostatic Hypotension.
Feb 27, 2012 Dermatologic and Ophthalmic Drugs Advisory Committee Meeting
March 12, 2012 Arthritis Advisory Committee Meeting
March 14, 2012 Pharmaceutical Sciences and Clinical Pharmacology Advisory Committee Meeting
March 28-29, 2012 Endocrinologic and Metabolic Advisory Committee Meeting.