AstraZeneca axes Moderna-partnered, phase 2 heart disease drug plus a Wee inhibitor

AstraZeneca has axed a Moderna-partnered cardiovascular disease candidate from its phase 2 pipeline. Months after reporting positive trends on exploratory efficacy endpoints, the Big Pharma has pushed the mRNA candidate out the door while also dropping its Wee1 inhibitor after many years of development.

The Moderna-partnered candidate is AZD8601, a therapy based on mRNA encoding vascular endothelial growth factor (VEGF-A). In a phase 2a clinical trial, results from which were reported late last year, investigators injected the mRNA directly into the myocardium of patients undergoing elective coronary artery bypass surgery. Seven patients received AZD8601, and four got placebo.

AstraZeneca hailed the results as positive, pointing to trends in the three exploratory endpoints, which looked at left ventricular ejection fraction, a biomarker that is elevated in heart failure and functional patient-reported outcomes. 

The readout offered early support for the use of AZD8601 to trigger production of  VEGF-A, a paracrine factor involved in new blood vessel formation and the production of specialized cells that contribute to repair and regeneration of the heart. However, AstraZeneca removed the asset from its phase 2 pipeline in its quarterly update (PDF). Moderna, the co-developer of AZD8601, still lists the candidate in its pipeline.

AstraZeneca also removed Wee1 inhibitor adavosertib from its phase 2 pipeline. The company has put the drug through an extensive clinical trial program since securing the rights to the candidate from Merck for $50 million upfront in 2013. Almost a decade later, AstraZeneca has removed adavosertib in ovarian cancer, solid tumors and uterine serous cancer, plus an Imfinzi combination, from its pipeline.

An academic group generated evidence of efficacy in a subset of colorectal cancer patients late last year. With adavosertib now off the agenda at AstraZeneca, other companies working on Wee1 may be the main beneficiaries from the efficacy signal. Zentalis Pharmaceuticals, with support from Pfizer, is moving its wholly owned Wee1 inhibitor ZN-c3 through the clinic.

AstraZeneca’s action comes shortly after Nuvation Bio deprioritized its Wee1 inhibitor NUV-569. The changes mean Zentalis is now up against a smaller pool of companies including Debiopharm and Impact Therapeutics in the race to market.