Otsuka’s guadecitabine has failed to enhance total survival in two section Three blood most cancers medical trials. Guadecitabine has now failed three late-phase trials, leaving Otsuka to weigh up the following steps for a hypomethylating agent it acquired in its $886 million takeover of Astex Prescription drugs.
One of many two trials that learn out this week, ASTRAL-2, enrolled sufferers with beforehand handled acute myeloid leukemia (AML). The opposite section Three trial, ASTRAL-3, enrolled beforehand handled sufferers with myelodysplastic syndromes or power myelomonocytic leukemia. In every research, sufferers acquired both guadecitabine, often known as SGI-110, or the physicians’ selection of other remedy.
Guadecitabine failed to enhance on the general survival of the management group in both inhabitants. The setback comes two years after Otsuka revealed guadecitabine had carried out no higher than management in a section Three trial of beforehand untreated AML sufferers who had been ineligible for intensive induction chemotherapy.
In disclosing the newest failures, Astex Chief Medical Officer Mohammad Azab, M.D., stated guadecitabine was linked to improved outcomes in sure subgroups, whereas acknowledging extra research could be wanted to validate that signal of efficacy. It’s unclear whether or not Otsuka will make the investments wanted to supply the validatory information. The Japanese drugmaker is at the moment evaluating its choices.
Astex and Otsuka moved guadecitabine into section Three within the perception it represented an enchancment over present hypomethylating medication, specifically Celgene’s Vidaza and their very own Dacogen. To enhance on first-generation hypomethylating brokers, researchers designed the prodrug formulation of Dacogen energetic ingredient decitabine to withstand degradation by cytidine deaminase, thereby enabling extra of its energetic metabolite to behave on most cancers cells and reverse aberrant DNA methylation.
The failure of guadecitabine in three section Three trials places a significant dent in that speculation and leaves Otsuka going through the prospect of being unable to generate a return on the lead medical program coated by its takeover of Astex. HSP90 inhibitor AT13387, the opposite experimental asset Otsuka singled out on the time of the takeover, is now not listed on Astex’s pipeline.
If Otsuka kills off guadecitabine, section Three prospect ASTX727, a fixed-dose mixture of decitabine and a cytidine deaminase inhibitor, will likely be Astex’s most superior program. Astex additionally has a twin IAP antagonist in section 2 and a few early-phase applications.