- A next-generation oncology drug from Otsuka Pharmaceutical has failed the first of three late-stage trials testing it against multiple blood cancers.
- Dubbed ASTRAL-1, the trial enrolled 815 adults with previously untreated acute myeloid leukemia (AML) who can't be on intensive induction chemotherapy. Participants either received Otsuka's guadecitabine — a prodrug that's supposed to expose tumor cells to the enzyme inhibitor decitabine for longer periods of time — or one of three physicians' choice control therapies, azacitidine, cytarabine or decitabine.
- Guadecitabine didn't yield significant improvements in the co-primary endpoints of complete response rate and overall survival, but Otsuka is still assessing safety data and whether its drug hit on any secondary endpoints.
Otsuka has devoted hundreds of millions of dollars in the past few years to build up its pipeline.
Just this month, the Japanese pharma dropped $430 million to snag private biotech Visterra, its antibody technology and a suite of preclinical drugs. The acquisition came about 15 months after Otsuka committed $100 million upfront to take over private biotech Neurovance and $50 million upfront to gain rights to Teva Pharmaceutical's closely watched migraine treatment fremanezumab.
Several years before those deals, however, Otsuka bought all the outstanding shares of Astex Pharmaceutical for around $886 million, handing it a marketed product in Dacogen (decitabine) and two leading clinical programs — one of which was guadecitabine. While company leadership isn't giving up on guadecitabine, the ASTRAL-1 data surely weigh on that high-priced transaction.
"The study used very strict criteria of ineligibility to receive intensive chemotherapy based on age (over 75 years) or poor performance status ... or comorbidities, which made it a difficult population to show superior benefit of guadecitabine," Mohammad Azab, chief medical officer at Astex, said in a July 30 statement.
Decitabine inhibits an enzyme that tacks on a methyl group to DNA. Research has shown that when too many methyl groups are added to certain regions of DNA, it can silence tumor suppressing genes and thereby give rise to cancer. As such, guadecitabine links decitabine with a nucleoside called guanosine that makes it more difficult to degrade, in theory creating a drug which allows for greater uptake of the active metabolite.
Despite the drug's initial Phase 3 failure, Otsuka intends to continue studying it in the Phase 3 ASTRAL-2 trial of relapsed or refractory AML patients following intensive chemotherapy, and the Phase 3 ASTRAL-3 trial of patients with relapsed and refractory myelodysplastic syndromes and chronic myelomonocytic leukemia.
To that point, Otsuka has also been increasing its R&D investment. The company spent 42.61 billion Japanese yen (about $380 million) on R&D from January through March, up 16% year over year.