UK drugmaker Antisoma saw its shares nosedive 65% on Monday as investors were left reeling on news that another of its key late-stage compounds failed to perform in a late-stage clinical trial, raising serious questions over its future.

In a huge blow to the firm, the Phase III ACCEDE trial of key drug AS1413 (amonafide) in secondary acute myeloid leukaemia failed to meet its primary endpoint, and consequently Antisoma said it has decided to pull the plug on further development of the drug, leaving a substantial gap in its R&D pipeline.

ACCEDE was a single pivotal, randomised, controlled trial in which a regimen of AS1413 and cytarabine was compared with standard therapy of daunorubicin and cytarabine in patients with secondary AML, i.e. following myelodysplastic syndromes or chemotherapy/radiotherapy treatment for another cancer. The primary endpoint of the trial was the rate of complete remission with or without recovery of normal blood counts.

"This is hugely disappointing for patients, investigators, investors and employees," said Antisoma's chief executive Glyn Edwards, and he stressed the company must now shrink its size and focus on maximising the value of its other development programmes to ride out the rough patch.

In Spring last year Antisoma's stock was battered by the failure of ASA404 (vadimezan) - which was partnered with Swiss drug giant Novartis - in a late-stage clinical trial with patients with lung cancer, after showing that the drug offered minimal survival benefit. In November Novartis decided to terminate development of the drug, leaving Antisoma with much of its hopes pinned on the now failed AS1413. 

"The difficulties faced by Antisoma reflect a broader problem in cancer drug discovery, where Phase 2 trials are too small and uncontrolled, and failures identifying the specific groups of patients on which to test drugs," said analyst Paul Cuddon at Peel Hunt, commenting on the failure, according to media reports. "Only when these problems are resolved do we see a future for small, focused cancer drug discovery companies", he added.

Antisoma's pipeline now houses just three programmes: AS1411, a novel aptamer drug with potential in blood cancers and solid tumours currently; DCAMs (dendritic cell autoimmune modulators), small-molecule kinase inhibitors in preclinical development with potential as oral therapeutics for autoimmune diseases; and PPMID, a new and highly targeted approach to cancer treatment in preclinical development in a collaboration with The Institute of Cancer Research.

At the end of the year, the company around £23.4 million in cash in its pocket, but following the failure of AS1413 said it plans to take immediate steps to reduce its expenditure significantly.