Trials for Precision Medicines

In the last few years, the advances in human biochemistry have finally turned into a flood of new therapies in the pipeline, including “precision medicine” drugs and cell therapies.  An article in Health Affairs reviews the process used to approve these therapies.   (HA Article)  Precision medicine uses knowledge about variations in DNA and other biochemical processes to develop and use drugs and treatments that at least theoretically could have greater benefits and less safety issues.  These therapies are often coupled with companion diagnostics that identify the population most likely to benefit from them and which are appropriate for their use.  These treatments are often eligible for special FDA status, such as orphan drug and breakthrough therapy designations.  The authors looked at the characteristics of FDA approvals for precision and non-precision therapies between 2013 and mid-2017.  They evaluated the trial characteristics and time to approval.  In the study period the FDA approved 151 novel therapeutics.  112 were approved as drugs and 39 as biologics.  64 had orphan designations, 39 had breakthrough therapy ones and 41 were for cancer.  33 of the drugs met the definition of precision medicines.

Significantly more of these precision therapeutics than standard ones received orphan, breakthrough, fast track, accelerated approval and priority review status, and more were indicated for cancer.  The total development and review time for these therapies was an average 5.8 years versus 7.5 for standard therapies.  The precision medicines had a median of only one pivotal trial, compared to two for non-precision ones.  They also enrolled a median of only 305 participants versus 584 for standard therapeutics.  The trials were less likely to be randomized, use placebo or a comparator.  The primary endpoints were surrogate measures for 96% of precision medicine pivotal trials, compared to only 49% for standard ones.   It is understandable that these therapies, which often target diseases with limited or no current treatment options, are receiving enhanced regulatory attention to speed them to the market.  On the other hand, the faster approvals with less substantial trials raises safety risks and also may create questions about the true efficacy of the therapies.  Post-approval studies with intensive data collection and analysis are a must; so that any risks can be promptly identified, as well as helping payers assess whether these therapies are worth paying for.