Industry promotion of oncology drugs with accelerated approval that failed confirmatory trials.

Abstract

11029 Background: Oncology drugs are commonly granted accelerated approval by FDA based on pivotal trials using surrogate markers as primary endpoints, while requiring sponsors to complete postapproval studies that confirm clinical benefit. Industry payments to physicians may influence treatment recommendations, which is particularly concerning for accelerated approval drugs, where clinical benefit remains uncertain. We investigated industry payments to physicians before and after results of confirmatory studies for oncology drugs with accelerated approval whose confirmatory studies failed to confirm clinical benefit. Methods: In this cross-sectional study, using Drugs@FDA database, we identified oncology drugs granted FDA’s accelerated approval, their required postapproval confirmatory studies, and FDA status changes (withdrawn or converted to traditional approval). We searched ClinicalTrials.gov, publications, and company press releases to identify drugs with confirmatory studies failing to confirm clinical benefit. We searched OpenPayments database to record industry payments made to physicians associated with these drugs. Results: From 2009-2021, of 73 drugs granted accelerated approval by U.S. FDA, 7 (9.6%) had indications for which all confirmatory studies were negative. Among these, 6 were voluntarily withdrawn following FDA’s recommendation, while for Pepaxto (melphalan flufenamide), the sponsor appealed FDA’s proposed withdrawal; it was ultimately withdrawn by FDA. Pepaxto was excluded from our analysis as it had no reported payments on OpenPayments. The results of postapproval confirmatory trials for the remaining 6 indications were announced after a median time of 4.2 (2.2-6.6) years. All 6 drugs were withdrawn from the market, with a median duration of 4.9 (IQR, 2.7-6.9) years from approval to withdrawal. Following announcement of negative postapproval confirmatory study results, average monthly payments received by all physicians increased for Marqibo (vinCRIStine sulfate) from $138 in the year preceding announcement to $164 during the period between announcement of negative results and market withdrawal, but decreased for Farydak (panobinostat) ($12,317 to $4,916), Blenrep (belantamab mafodotin) ($152,417 to $119,394), and Ukoniq (umbralisib) ($23,139 to $14,130). Lartruvo (olaratumab) and Aliqopa (copanlisib) had almost no payments after announcement of negative confirmatory study results. Conclusions: Industry payments for oncology drugs with accelerated approvals mostly decreased after announcement of negative confirmatory trial results; however, there was evidence of continued promotion for certain drugs until a request for voluntary withdrawal was made by FDA. This suggests that regulatory oversight and enforcement might be necessary to mitigate ongoing promotion of such drugs after confirmatory trials fail to confirm clinical benefits.