Bristol Myers' RayzeBio pauses radiotherapy trial due to isotope shortage

RayzeBio, a key player in Bristol Myers Squibb's recent $4.1 billion radiopharmaceutical acquisition, has encountered a significant obstacle in its nuclear medicine endeavors due to a shortage of the isotope actinium. As a result, the company has temporarily paused new patient enrollment in its ACTION-1 phase 3 trial, which is evaluating RayzeBio’s lead radiotherapy candidate, RYZ101. This trial focuses on treating somatostatin receptor (SSTR) expressing gastroenteropancreatic neuroendocrine tumors (GEP-NETs) in patients who have previously undergone lutetium-177 based somatostatin therapies.

RayzeBio's radiotherapy platform, including RYZ101, utilizes an alpha-emitting isotope known as actinium-225 (Ac225). This differentiates their approach from existing radiotherapies like Novartis’ Lutathera and Pluvicto, which use a beta-emitting isotope called lutetium. Actinium-225’s supply issues have forced RayzeBio to halt new enrollments temporarily, although the company expects to resolve these constraints by the first quarter of next year. In the meantime, patients already enrolled in ACTION-1 will continue receiving treatment, with plans to resume new patient enrollment by the third quarter.

The news of the enrollment suspension was first reported by Endpoints. RYZ101 represents a major asset in BMS' acquisition of RayzeBio, announced late last year when BMS agreed to pay $62.50 per share, roughly doubling the value of RayzeBio’s stock at the time. BMS' Chief Medical Officer for Drug Development, Samit Hirawat, M.D., highlighted the promise of radiopharmaceuticals, describing them as among the most promising and rapidly growing methods for targeting solid tumors.

Beyond the clinical potential of RayzeBio’s platform, the acquisition was also driven by the construction of a 63,000-square-foot manufacturing facility in Indianapolis, aimed at producing actinium-225. RayzeBio is investing significantly in this capability, recognizing the premium value placed on radiopharmaceutical companies that control their manufacturing processes. The acquisition was finalized in late February, making RayzeBio a wholly owned subsidiary of Bristol Myers Squibb.

Radiopharmaceuticals are increasingly gaining traction in the oncology arena. Novartis has been a pioneer in this field, expressing optimism about a new $1 billion market opportunity following the NETTER-2 trial. This trial demonstrated that Lutathera significantly reduced the risk of disease progression or death by 72% in newly diagnosed patients with grade 2 or 3 advanced GEP-NETs that are SSTR-positive. Additionally, Novartis is preparing to submit an FDA application to expand the use of Pluvicto for earlier treatment of prostate cancer.

The surge in interest in nuclear medicine has also attracted manufacturers and suppliers. For instance, CDMO Nucleus RadioPharma recently secured its first commercial contract to produce ARTBIO’s Pb212-radiolabeled therapies at its facility in Rochester, Minnesota. Furthermore, Bayer has partnered with PanTera to supply actinium-225 for clinical trials starting in the latter half of 2024.

In summary, while RayzeBio's temporary halt in new patient enrollment due to actinium-225 shortages poses a challenge, the company remains optimistic about overcoming these supply issues soon. The broader field of radiopharmaceuticals continues to see significant advancements and investments, underscoring its growing importance in cancer treatment.