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.
|Selected MCL-1 inhibitors|
|MIK665/S64315||Novartis/Servier (ex Vernalis)||NCT04629443||Azacitidine combo in AML|
|NCT03672695||Venclexta combo in AML|
|NCT04702425||VOB560 (Bcl2 inhibitor) combo|
|AMG 176||Amgen/Beigene||NCT02675452||Earlier voluntarily halted, now enrolling again|
|NCT03797261||Venclexta combo, trial suspended for lack of safety in Sep 2019|
|AMG 397||Amgen/Beigene||NCT03465540||Put on hold for cardiac tox; now terminated|
|AZD5991||Astrazeneca||NCT03218683||Trial put on hold after cardiovascular parameter elevations with Venclexta combo|
|ABBV-467||Abbvie||NCT04178902||Trial terminated for "strategic considerations"|
|PRT1419||Prelude Therapeutics||NCT04543305||Started Sep 2020|
|GS-9716||Gilead Sciences||NCT05006794||Started Sep 2021|
|Source: Evaluate Pharma & clinicaltrials.gov.|
This story was updated to add comment from Astrazeneca.