Merck KGaA has teamed up with J. Craig Venter’s Human Longevity, Inc. (HLI) to identify biomarkers that suggest melanoma patients will respond to pimasertib. The agreement follows a two-year lull in development of the MEK1/2 inhibitor precipitated by mixed data from a phase 2 trial.
HLI’s task is to sequence tumor and germline DNA from clinical trial participants. The large-scale genomics shop will then apply its data analysis capabilities to the results and other sources of information on survival and clinical outcomes. Merck hopes generating and contextualizing the sequencing data will lead to the identification of treatment response biomarkers for pimasertib in patients with advanced NRAS-mutated cutaneous melanoma.
The German drug developer tested pimasertib in 194 such patients in a phase 2 trial. Data posted last year linked pimasertib to a statistically significant improvement in progression-free survival (PFS) over the chemotherapy dacarbazine. Participants who took pimasertib recorded a median PFS of 13 weeks, as compared to 7 weeks among the subjects who received dacarbazine.
That difference was big enough for the trial to meet its primary endpoint. Pimasertib also bested dacarbazine in terms of overall response rate. But the MEK1/2 inhibitor failed to move the needle in terms of overall survival (OS). The pimasertib arm recorded a median OS of 8.9 months. The dacarbazine cohort beat that figure with a median OS of 10.6 months.
The importance of such weak OS data to the prospects of pimasertib were made clear last month when Array BioPharma pulled the NDA for its rival drug binimetinib. A phase 3 trial of binimetinib in NRAS-mutant advanced melanoma linked the MEK inhibitor a PFS of 2.8 months, compared to 1.5 months for dacarbazine. But binimetinib came up short against the OS endpoint. The OS for the experimental drug was 11 months, compared with 10 months for dacarbazine.
After talking to the FDA, Array concluded the trial had failed to demonstrate the clinical benefit needed to win approval. Pimasertib must perform better in future trials than it did in the phase 2 if it is to avoid a similar fate. One way to achieve such a boost is to limit enrollment to patients who are genetically predisposed to responding positively to the drug.
HLI and Merck described their work to discover biomarkers that identify such patients as a pilot project. The deal leaves the door open for further projects that apply HLI’s genomics capabilities to Merck’s pipeline.
Merck is one of several Big Pharma companies to publicly partner with HLI. Roche’s Genentech struck a deal in 2015 to have HLI sequence and analyze tens of thousands of patient samples. AstraZeneca dialed up the scales further still last year by tasking HLI with sequencing and analyzing up to 500,000 samples from its clinical trials over the next decade.
The companies, like peers such as Amgen and Regeneron, are looking to sequencing data to uncover new R&D opportunities and better target drugs in their pipelines and portfolios.