The Compassionate Use Advisory Committee (CompAC) for development of pre-approval access to investigational drugs.

e18001 Background: In May 2015, CompAC was formed at NYU to provide guidance fairly and transparently on allocating a limited supply of , Daratumumab, to patients outside of clinical trials. Janssen, manufacturer of Daratumumab, was receiving numerous pre-approval requests for access to the drug. Daratumumab (Darzalex) was approved in the U.S. for treatment of patients with multiple myeloma who have received at least one prior therapy and approved by EMA for monotherapy. The SPR program was phased out based on country level approvals, with requests and submissions managed in a regulatory and legal environment.Methods: CompAC was 10 medical experts, bioethicists, and patient advocates; ethical and medical principles for review and process guidelines developed. Weekly meetings were held to consider SPR requests, with 3 members voting each week. After U.S. approval, requests for drug were considered only from countries where Janssen was seeking but had not gained approval. Recommendations were conveyed weekly for final decisions. Results: A total of 331 cases were received by Janssen of which 5 withdrew and 2 expired, leaving 324 cases for review. Of these, 180 were sent to CompAC and 163 were recommended by CompAC for treatment. Janssen approved all 163. CompAC recommended declining 17 of these cases; Janssen declined 15 (2 cases were approved based on additional information provided). Of the 144 patients excluded by Janssen before CompAC review, 27 were due to low benefit/risk profile, 17 provided incomplete clinical information, 42 for other variables, 46 received alternative therapies, 10 for referral to another pre-approval access channel, and 2 commercially available drug. Of the cases that CompAC recommended declining, 11 were due to low benefit/risk profile, for 3 alternative therapies available, and remaining 3 for miscellaneous reasons. Requests were received from 13 countries, the majority from outside the U.S.Conclusions: CompAC was successfully implemented and provided rapid review of SPR requests for pre-approval Daratumumab access. Janssen is extending CompAC to other relevant assets. Other companies are considering the model.