Immuno-oncology is a unique approach to cancer treatment that leverages the body’s immune system to help fight cancer. In recent years, immune checkpoint inhibitors have changed the landscape of immunotherapy, and emerging therapies such as chimeric antigen receptor T-cells (CAR-T), dendritic cell vaccines and bi-specific T-cell engager (BiTE) antibodies are pushing the envelope even further.
Today’s competitive oncology drug development space is evolving rapidly, with high stakes for sponsors and participants alike. An increasing number of novel new oncology drugs are in development—precision medicines and immunotherapies such as immune checkpoint inhibitors, CAR-T cell therapies, and oncolytic viruses—that leverage genomic insights. Many more applications than in the past are also qualifying for the FDA’s expedited approval programs. Needless to say, in this race for novel drug approvals, the complexity of oncology trial design and execution has increased dramatically.
The recent FDA approval of Sarepta’s eteplirsen (Exondys 51), while generally welcomed in the Duchenne muscular dystrophy (DMD) community, was not without controversy. Eteplirsen is a gene therapy drug for use in DMD patients whose dystrophin mutation is amenable to exon 51 skipping. It was approved after a study of 12 patients, four of whom received placebo for 24 weeks before being re-randomized to one of two dosages. Questions have arisen regarding the use of historical data as a control in the absence of a concurrent placebo arm of the latter part of the study, the efficacy measures used, and the use of post-hoc analyses conducted by the study sponsors. But in the end, Eteplirsen was approved by the FDA, and the process, regardless of attendant controversy, illustrated the potential for innovation in clinical trial design and methods of analysis.
Novel therapeutics such as gene and cell therapies, nanoparticles, and combination products requiring targeted delivery, novel treatments for wound healing, cardiovascular disease, and bone regeneration, and new medical device technologies call for innovative surgical procedures in preclinical trials to determine safety and efficacy.