Otsuka’s $886M-plus drug just flopped in its first crucial PhIII trial for frontline AML

Five years ago Otsuka swept in and scooped up California-based Astex for $886 million, determined to get its hands on their promising leukemia drug SGI-110 as it plugged the operations into its global R&D ops. Now the drug is called guadecitabine, and it just flopped in the first pivotal Phase III study, crashing co-primary endpoints for complete responses and overall survival for frontline use among advanced patients with acute myeloid leukemia.

The drug is billed as a next-generation DNA hypomethylating agent, but it failed against a group of patients who received one of several alternative therapies: azacitidine, decitabine, or low dose cytarabine.

Mohammad Azab

Otsuka was pulled in by promising mid-stage data on the drug, confident that it had the kind of proof-of-concept data in humans that justified an ambitious Phase III program. The Japanese company now has two other Phase III studies — ASTRAL-2 and ASTRAL-3 — in the clinic for advanced AML and myelodysplastic syndromes, MDS, or chronic myelomonocytic leukemia.

Otsuka kept Astex on as a subsidiary, with its headquarters and development work in Pleasanton, CA, and its discovery and preclinical effort based in Cambridge, UK. The company has been vexed by failures on Alzheimer’s, where it’s partnered with Lundbeck. But Otsuka also recently nabbed Visterra in a $430 million deal, with plans to add that Waltham, MA-based biotech to the global network.

“We are disappointed in the outcome of the ASTRAL-1 study,” said Astex CMO Mohammad Azab. “The study used very strict criteria of ineligibility to receive intensive chemotherapy based on age (over 75 years) or poor performance status (ECOG PS of 2 or 3) or comorbidities, which made it a difficult population to show superior benefit of guadecitabine. ASTRAL-1 is the largest global prospective study ever conducted in this specific patient population with low intensity therapy, with 815 patients randomized, of whom about 90% were treated with hypomethylating agents or HMAs (guadecitabine, azacitidine, or decitabine).

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