Bristol Myers Squibb announced on October 12 that RYZ101, the actinium-225 radiopharmaceutical developed by its RayzeBio unit, met the primary endpoint of the Phase 3 ACTION-1 trial at a planned interim analysis. The study showed a statistically significant and clinically meaningful improvement in progression-free survival, assessed by blinded independent central review, in patients with somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors whose disease had progressed after lutetium-177 based therapy.
ACTION-1 randomized patients to RYZ101, also written as 225Ac-DOTATATE, or investigator’s choice of standard care, which included high-dose or high-frequency long-acting somatostatin analogues, everolimus or sunitinib. The company said safety results were consistent with the known profile of RYZ101, but it did not disclose the size of the progression-free survival benefit in the topline release.
RayzeBio’s chief medical officer described the result as the first from a Phase 3 trial of an alpha-isotope targeted radiopharmaceutical in any indication, and said the company is moving to bring the data to the FDA. That claim matters commercially because the established radioligand in this space, Novartis’s Lutathera, uses the beta emitter lutetium-177. A therapy that works after lutetium therapy fails would extend the radiopharmaceutical sequence rather than compete for the same first slot.
The readout arrived the same morning as Bristol Myers’s admilparant results in idiopathic pulmonary fibrosis, which are covered in a separate story from October 12. Together the two readouts de-risk different parts of the late-stage pipeline, oncology radiopharmaceuticals on one side and respiratory on the other, ahead of the company’s third-quarter earnings on October 29. The open questions are the ones topline releases never answer: the hazard ratio, the durability of response, and how the FDA views an interim analysis as the basis for a filing.