Pfizer is axing one of the assets it picked up in the $11.4 billion takeover of Array BioPharma three years ago. After carrying out a phase 3 interim futility analysis, the Big Pharma has decided to stop work on the cardiovascular disease candidate PF-07265803.
The phase 3 clinical trial predates the takeover, with Array kicking it off in 2018, but Pfizer had embraced the program, hailing (PDF) the work on PF-07265803 for dilated cardiomyopathy with lamin A/C gene mutation as part of its growing leadership in rare cardiology. Because the condition is associated with activation of the p38 MAPK kinase, Pfizer bet that inhibiting the pathway could improve performance on the six-minute walk test.
That hypothesis failed to survive an interim futility analysis. With the phase 3 trial on course to fail, Pfizer is stopping the study and further development of PF-07265803. The blow follows delays to the trial that caused its targeted primary completion date to slip from 2023 to 2024. The company increased the enrollment target from 160 to 200 in March.
Array moved the candidate into phase 3 on the strength of a midphase study that found recipients of the drug experienced a 69-meter mean absolute change from baseline on the six-minute walk test after 12 weeks of treatment, seemingly validating the idea that inhibition of the p38 MAPK pathway can improve function. In mice, the drug candidate normalized left ventricular morphology.
The failure to translate the effects into humans is a blow for patients with LMNA-related dilated cardiomyopathy, 70% of whom have cardiac death, a heart transplant or a major cardiac event by the age of 45. There are no disease-specific treatment options for patients with the rare disease.
For Pfizer, the failure wipes out a pillar of its rare cardiology strategy, but PF-07265803 was never the main motivation for the Array deal, which the Big Pharma struck to get its hands on the cancer medicines Braftovi and Mektovi. Pfizer made no mention of PF-07265803, then known as ARRY-797, in the original presentation (PDF) to discuss the Array deal, although an analyst did ask (PDF) about it during the Q&A.