The impact of newly approved drugs on clinical and operational strategies for multiple myeloma clinical trials.

Abstract

e19511 Background: The global burden of multiple myeloma (MM) has increased steadily in last 3 decades. The IARC reports there were ~160,000 new cases worldwide in 2018. There has been an increase in the development and approval of more effective targeted therapy options (new immunomodulatory agents, proteasome inhibitors, and monoclonal antibodies); this, coupled with high adoption of these therapies presents a major challenge in enrollment of current ongoing clinical trials. We assessed the impact of near-term regulatory approvals on clinical trial enrollment. Methods: Public domain clinical trial enrollment data from MM studies (Phase I, I/II, II) closed/completed between 2011-2018 were used to determine enrollment trends pre and post 2014. We leveraged real-world medical claims data to project/model adoption of recently approved drugs in the U.S.; additionally, drug sales volume data was used to evaluate ex-US national adoption trends. The utilization rates of 5 recently approved drugs by regimen and line of treatment was determined. Results: In the U.S., there is a 13% increase in median enrollment duration with a corresponding 25% decrease in median p/s/m enrollment in MM studies, irrespective of phase, where enrollment was completed between 2015 -2018 compared to 2011-2014. We hypothesize that one of the factors for this increase in enrollment timeline is the approval and adoption of newly approved therapies post 2014. Two of the five recently approved drugs show a steady increase in the number of patients treated over 2016, 2017 and 2018, while one of the drugs plateaus over the same period. Outside of the U.S., our analysis confirms the existence of gaps in time to approval /adoption of recently approved drugs; for example, we observe a two-year delay in approval/adoption for one of the drugs in France compared to the other countries in Western Europe. Conclusions: There are over 10 investigational MM drugs currently in development which are anticipated to be granted approval between 2019-2021. Factoring the real-world adoption of near-term drug approval into global clinical and operational strategies offers insights into mitigating potential future enrollment challenges.