Low-key Astra hold puts spotlight on Novartis and Servier

A low-key US clinical hold yesterday suggests more problems for the MCL-1 inhibitor drug class. The phase 1 trial of AZD5991, Astrazeneca’s inhibitor of this anti-apoptosis regulator, has been put on hold after "asymptomatic elevation in cardiovascular laboratory parameters" was seen in a patient treated in combination with Venclexta, a spokesperson said. Though the elevation resolved, the issue is relevant because two years ago Amgen halted its rival anti-MCL-1 agent AMG 397 after seeing cardiac toxicity. Astra stressed that the patient had other co-morbidities, but nevertheless it is impossible to ignore the possibility of a class effect. The companies most invested in MCL-1 inhibition are probably Novartis and Servier, which have a joint project, MIK665, in phase 1/2. New clinical entrants since Evaluate Vantage last analysed the space include projects from Abbvie – though this too has now been scrapped – Prelude Therapeutics and Gilead, while the private group Anji has a preclinical asset. Amgen, meanwhile, has canned AMG 397, though it insists that this was for “strategic” and not “safety” concerns; its second MCL-1 inhibitor, AMG 176, is in two phase 1 trials, one of which is still suspended for lack of safety.

This story was updated to add comment from Astrazeneca.