Bristol Myers' RayzeBio halts radiotherapy trial enrollment after isotope runs scarce

It’s no secret that the field of nuclear medicine has occasionally been hamstrung by supply constraints. Now, RazyeBio, the company at the center of Bristol Myers Squibb’s recent $4.1 billion radiopharmaceutical buyout, is learning that reality the hard way.

Thanks to a shortage of the isotope actinium, RayzeBio has temporarily halted new patient enrollment in its ACTION-1 phase 3 study, a RayzeBio spokesperson confirmed over email.

The trial is assessing the ability of RayzeBio’s lead radiotherapy candidate, RYZ101, to help treat somatostatin receptor (SSTR) expressing gastroenteropancreatic neuroendocrine tumors (GEP-NETs) in patients who have already received treatment with lutetium-177 based somatostatin therapies.

RYZ101 and the rest of RayzeBio’s platform leverages an alpha-emitting isotope called actinium-225 (Ac225). The approach differs from approved radiotherapies such as Novartis’ Lutathera and Pluvicto, which use a beta-emitting isotope known as lutetium.

“We are rapidly advancing toward on-site production of Ac225 and anticipate the ability to support ongoing clinical supply by Q1,” the company's spokesperson said.

All patients currently enrolled in ACTION-1 will continue to receive treatment, RayzeBio's spokesperson stressed. The company plans to resume new patient enrollment in the third quarter.

Endpoints first reported the news of the enrollment pause on Sunday. 

RYZ101 is the crown jewel in BMS’ RayzeBio acquisition, which the Big Pharma company unveiled late last year. At the time, BMS said it would pay $62.50 per share of RayzeBio—about double where the San Diego-based biotech’s stock was trading at the time—for a total equity value of $4.1 billion.

At the time of the deal announcement, BMS’ chief medical officer for drug development, Samit Hirawat, M.D., noted that radiopharmaceuticals represent one of the “most promising and fastest-growing” new modalities for attacking solid tumors.

Aside from the clinical promise of RayzeBio's platform, BMS was also enticed by the fact that RayzeBio was on the cusp of completing the build-out of a 63,000-square-foot manufacturing facility in Indianapolis.

On its website, RayzeBio says it is investing in the ability to produce actinium-225 at the site.

When the buyout was first announced, William Blair analysts suggested that the deal “reemphasizes the premium value ascribed to pure-play radiopharmaceutical companies that have ownership over manufacturing.”

The acquisition closed in late February, making RayzeBio a wholly owned subsidiary of Bristol Myers. 

Radiopharmaceuticals are becoming quite the hot commodity in oncology, and Novartis continues to be on the forefront of that charge.

In January, the Swiss pharma expressed hopes that new data would open a $1 billion market opportunity after the company’s NETTER-2 trial found that Lutathera slashed 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.

And, in April, Novartis said it was preparing to submit an FDA application to expand its other radiotherapy, Pluvicto, into earlier treatment of prostate cancer.

Manufacturers and suppliers have been getting in on the nuclear medicine boom, too.

CDMO Nucleus RadioPharma recently inked its first commercial contract to help manufacture ARTBIO’s Pb212-radiolabeled therapies from its facility in Rochester, Minnesota.

Meanwhile, Bayer recently entered a pact with PanTera to help supply actinium-225 for clinical trial needs starting in the second half of 2024.