Food and Drug Administration
Center for Drug Evaluation and Research
Arthritis Advisory Committee
Gaithersburg Holiday Inn, 2 Montgomery Village Avenue, Gaithersburg, MD
August 16, 2001
BLA STN 103950 KineretÔ , (anakinra), Amgen, Inc.
SAFETY(in absence of TNF agents)
Patients receiving anakinra in the absence of anti-TNF blocking agents experienced a 3 fold higher rate of leukopenia across all studies (12% anakinra, [95% CI 9.9-15%] vs 5% placebo, [95% CI 2.5-9.2%]), a higher rate of serious infections in one study (2.1% anakinra [95% CI 1.3%-3.1%%] vs. 0.4% placebo [95% CI .01-2.0%]), and, frequently, injection site reactions. Although nearly 2000 patients have been treated with anakinra, only 175 have received the product for one year or longer.
Please discuss these safety data, particularly with regard to:
agents. Are additional studies needed to further characterize this risk? If so, what
types of studies should be conducted?
EFFICACY AND SAFETY
Anakinra was shown to provide higher ACR 20 response rates than placebo in a large randomized controlled trial (38% vs. 27% respectively, p<0.01). Clinical data from other smaller randomized studies was also supportive of the clinical efficacy of anakinra. Relatively few patients experienced ACR 50 responses (17% anakinra vs. 8% placebo) or ACR 70 responses (14% vs. 5%), however.
USE IN COMBINATION WITH OTHER IMMUNOMODULATORY AGENTS
It is likely that anakinra will sometimes be used in combination with other therapeutic agents, including anti-TNF agents. Safety data for the combination of anakinra with etanercept are very limited. Data from one small open-label study showed a relatively high rate of patient withdrawal from study (21/58) and serious adverse events (7/59), including four serious infections.
Please discuss these safety data:
The December 1998 Regulations require studies in pediatric patients if the drug or biological therapy that is or will be marketed for adults is likely to be used in substantial number of pediatric patients or represents a meaningful therapeutic advance. Anakinra has not yet been studied in pediatric patients. Etanercept is licensed for pediatric patients (as young as 4 years of age) with polyarticular onset JRA, a long term registry is underway, and studies are in progress in patients with other forms of JRA. Remicade is also being studied in pediatric patients with JRA.