Pembrolizumab,Pre-clinical development,Bristol-Myers Squibb,Non-small-cell lung carcinoma,Oncology,Food and Drug Adminis

Precision Immuno-Oncology Adoption Challenges

December 27, 2016

Considerations for the Successful Development of Precision Immuno-Oncology Therapies and Their Companion Tests Immuno-oncology has recently been characterized by one leading investor as a “Strategic Supernova”1. The associated excitement is well-supported by clinical trial data for some of the 70 or so clinical and preclinical programs targeting the PD-1/PD-L1 axis alone, across over 500 open clinical trials1. However, it is also evident that the abundance of developmental compounds will face considerable differentiation and cost-effectiveness challenges in global markets, a fact recently highlighted by Richard Padzur, M.D., acting director, Oncology Center of Excellence at the FDA2. Successful development and implementation of companion/complementary diagnostic strategies will likely mark the difference between winners and losers in this crowded space. A key 2016 report3 sponsored by BIO quantified an increase from 8.4% to 25.9% in likelihood of successful transition from Phase I to ultimate FDA approval resulting from a targeted development approach. Inclusion of a biomarker may not in itself completely address the differentiation challenge, however, as Bristol-Myers Squibb (BMS) found when the Checkmate 026 1st line NSCLC trial failed to meet its primary endpoint for its Opdivo therapy. In this scenario, the low (5%) cut-off of the PD-L1 biomarker, which resulted in the inclusion of 78% of patients in the trial, appeared to provide insufficient enrichment. By contrast, Merck had previously reported Keynote 024 trial success of its Keytruda therapy in the same (1st line NSCLC) setting using a (different) PD-L1 test which selected only 30% of patients using 50% stained cells as a cut-off. Release of the BMS trial data in August resulted in nearly $20 billion of market value changing hands, in what might be considered a value inflection point for the broader field of precision medicine. Meeting the regulatory bar will not suffice in an increasingly cost-constrained world. Indeed, the U.K.’s National Institute of Health and Care Excellence (NICE) highlighted the lack of cost-effectiveness of Opdivo in the unstratified 2nd line NSCLC setting in its October negative draft guidance4—despite previous approvals by regulators for use of the drug in this setting. Within the same draft guidance, NICE invited the company to submit additional evidence in biomarker-positive (PD-L1 >10%) patients, with potential interim coverage being provided under the new managed access Cancer Drug Fund mechanism. This proposed path would offer the potential for full-market access within two years in a biomarker-defined subset representing about one-third of the population. Adoption of such criteria is likely to become...

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