Challenges in confirming drugs like Aduhelm after early approval

Early approval pathways for drugs – intended to strike a compro­mise between access to promising therapies today, and confirmatory evidence tomorrow – often result in access accompanied by a persistent lack of evidence of benefit, write Holly Fernandez Lynch and Christopher T. Robertson in a Policy Forum. This issue is especially concerning as patients in myriad disease areas push for early drug approvals, as was recently done for Aduhelm, a treatment for Alzheimer’s disease. Through its 2021 ap­proval of Aduhelm (aducanumab), the US Food and Drug Administration (FDA) showed a willingness to embrace early ap­proval pathways in ways that risk the FDA’s reputation, write Lynch and Robertson. To improve the balance between access and proof, they say, experts must under­stand why post-approval studies often floun­der. The authors identify two primary challenges to early approval pathways: (1) insufficient company incentives to pursue rigorous post-approval trials; and (2) insufficient patient incentives to participate in such trials. Both of these challenges call for different policy solutions; the authors provide several. Continued acceptance of early approval pathways should be based on evidence regarding whether, when, and how meaningful post-approval trials will be possible, they emphasize. Accelerated approval is an important regulatory pathway worth trying to save, if the evidence suggests that meaningful improvements in confirmatory trials are possible.