The top management of Antisoma has stepped down, as the British cancer specialist cut its operations following the failure of its two leading drug candidates, Reuters reported.

The company's leukemia drug candidate AS1413 failed in a final-stage trial in January, delivering a second blow after the failure of a lung cancer drug, its biggest hope, in March 2010.

Chief Executive Glyn Edwards and finance director Eric Dodd both resigned, the company said, although Dodd will continue to advise the firm on strategic options, including a sale of the company.

January’s phase III ACCEDE trial of AS1413 (amonafide) in secondary acute myeloid leukemia failed to meet its primary endpoint, and consequently Antisoma decided to pull the plug on further development of the drug, leaving a substantial gap in its R&D pipeline, according to PharmaTimes. "This is hugely disappointing for patients, investigators, investors and employees," Edwards said.

In March 2010, ASA404 (vadimezan)--which was partnered with Swiss drug giant Novartis--failed in a late-stage clinical trial in 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 II 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."

Antisoma's pipeline now houses just three programs: AS1411, a novel aptamer drug with potential in blood cancers and solid tumours; 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.