The development of the lead drug behind Bristol Myers Squibb’s recent $4.1 billion acquisition of RayzeBio has hit delays, because of supply issues of a rare radioactive isotope crucial to the experimental treatment.
In response to questions from Endpoints News, Bristol Myers said it had paused enrollment of new patients in the Phase 3 trial of the radiopharmaceutical agent RYZ101, which is being tested for neuroendocrine tumors. A spokesperson cited an actinium supply shortage for the ACTION-1 enrollment pause.
“All currently enrolled patients will continue to receive treatment,” the spokesperson wrote in an email.
The company said it expects new patient enrollment in the Phase 3 to restart in the third quarter, and it anticipates “the ability to support ongoing clinical supply” by the first quarter of next year. Bristol Myers is also conducting a Phase 1b trial in patients with certain forms of small cell lung cancer. That study is still screening patients.
When it started the Phase 3 last May, RayzeBio said its treatment could become the first approved actinium-based radiopharmaceutical. Actinium-225 is a very rare isotope, so supply concerns are not new. But the shortage could add to questions about a future commercial rollout, and makers of other radiopharmaceutical treatments have sometimes struggled to meet demand. No actinium-based radiopharmaceutical treatments have been approved by the FDA yet.
“They were wise to pause the study. Hopefully, the trial of this exciting therapy can proceed soon,” Mayo Clinic Rochester’s chair of nuclear medicine Geoff Johnson told Endpoints News. “There was only one supplier of [actinium] for the study. Building redundancy with multiple vetted suppliers and FDA sign off to proceed takes time. This is an evolving field.”
Johnson is an investigator on the RYZ101 trials.
Radiopharmaceuticals are one of the hot areas in cancer, led by Novartis’ approved lutetium-based treatments Pluvicto and Lutathera. In addition to Bristol Myers’ deal for RayzeBio in December, Eli Lilly, Bristol, Novartis and AstraZeneca have all made billion-dollar or larger acquisitions in recent months. Some of those acquired startups are developers of actinium-based treatments, including Novartis’ $1 billion upfront move for Mariana Oncology.
Currently, Novartis, Johnson & Johnson and Lilly all have ongoing Phase 1 studies for actinium-based therapies. Fusion Pharmaceuticals, which AstraZeneca plans to acquire, is in Phase 2 studies of an actinium-based treatment for prostate cancer.
With an insufficient supply for clinical trials, there could be a bottleneck for such radiopharmaceuticals from getting to market, NorthStar Medical Radioisotopes CEO Frank Scholz told Endpoints last fall.
“Everyone’s waiting for a commercial GMP grade supply chain to become available for actinium,” Ariceum CMO Germo Gericke told Endpoints earlier this year.
Ken Song, who led RayzeBio until its acquisition by BMS, told Endpoints earlier this year that he believes radiopharmaceuticals will “become a major modality similar to what we’ve seen with antibody-drug conjugates.” He also thought the industry would “see a lot more availability of actinium isotope, which should also remove some of the barriers or obstacles that have been present historically to be able to do discovery and development.”