BMS, RayzeBio halt radiotherapy trial due to isotope shortage

The development of a promising new cancer treatment has hit a snag due to a shortage of a critical radioactive isotope.

BMS, which recently acquired RayzeBio for $4.1 billion, has paused enrollment of new patients in the Phase 3 trial of the radiopharmaceutical agent RYZ101. The experimental treatment is being tested for neuroendocrine tumors.

"All currently enrolled patients will continue to receive treatment, but we have paused enrollment of new patients in the Phase 3 trial of RYZ101 due to a shortage of actinium, a rare radioactive isotope that is crucial to this therapy," said a BMS spokesperson to Endpoints News.

The company expects new patient enrollment to restart in the third quarter of this year and anticipates being able to "support ongoing clinical supply" by the first quarter of 2024. BMS is also conducting a separate Phase 1b trial of RYZ101 in small cell lung cancer patients, still screening new participants.

Actinium-225, the specific isotope used in RYZ101, is exceedingly rare, which has long been a concern for developers of actinium-based radiopharmaceuticals.

"There was only one supplier of [actinium] for the study. Building redundancy with multiple vetted suppliers and FDA sign off to proceed takes time," explained Geoff Johnson, chair of nuclear medicine at the Mayo Clinic Rochester, to Endpoints News.

Johnson, an investigator on the RYZ101 trials, said, "They were wise to pause the study. Hopefully, the trial of this exciting therapy can proceed soon."

The actinium shortage underscores the challenges facing the burgeoning radiopharmaceutical industry.

"We are not experiencing a shortage. Because of our early entry into the space and the strategic partnerships we executed, we believe we have an advantage in this regard," argued Fusion Pharmaceuticals, which is developing its own actinium-based therapy.

However, NorthStar Medical Radioisotopes CEO Frank Scholz warned last fall that, with insufficient supply for clinical trials, "there could be a bottleneck for such radiopharmaceuticals from getting to market."

Germo Gericke, CMO of Ariceum, echoed this sentiment: "Everyone's waiting for a commercial good manufacturing practice-grade supply chain to become available for actinium."

Despite the current setback, RayzeBio's former CEO, Ken Song, remains optimistic about the future of radiopharmaceuticals.

"I believe radiopharmaceuticals will become a major modality similar to what we've seen with antibody–drug conjugates,” Song said earlier this year. “And we should 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."