RayzeBio advised investors last year it could face problems securing actinium isotope from a Russian supplier that it relies on for international studies.
Bristol Myers Squibb announced plans in December to acquire RayzeBio for $4.1 billion. It has since had to pause new patient enrollment in a Phase 3 trial as a result of an isotope shortage. The pause was first reported Sunday by Endpoints News.
During its few months as a public company in 2023, RayzeBio disclosed the potential risks of working with the unnamed actinium supplier in Russia, saying that it “must rely on our supplier in Russia for our international operations.” At that time, RayzeBio said it also used actinium supplied by the Department of Energy, though that supply can’t be utilized for clinical studies outside the US.
Bristol Myers Squibb declined to disclose its current third-party actinium suppliers for Ac225 but noted that it had several suppliers.
However, a trial investigator on Sunday told Endpoints there is only one Ac225 supplier for the global Phase 3 study in question. BMS did not answer when asked if the supplier was in Russia.
The pause in the Phase 3 trial could upend the time it could take for BMS to potentially bring the first actinium-based radioligand treatment to market amid palpable excitement about the promise of these cancer treatments. It also shows the field still has work to do to meet the growing demand for radiopharmaceuticals, which come with unique supply chain and manufacturing challenges, even as drugmakers like BMS and AstraZeneca have put billions of dollars into buying radiopharma companies.
“Supply chain, while improving, remains one of the most difficult topics for investors to do diligence on,” William Blair analysts wrote Monday in a note about the radiopharmaceutical sector.
Radiopharmaceuticals direct a radioactive isotope to tumor cells in order to kill them. These isotopes degrade over time, which means the therapies can’t be stockpiled. Some experts have dubbed actinium-225 the “goldilocks” of radiopharmaceuticals — it’s believed to be more potent than previous radioactive isotopes used for these treatments and has a half-life of 10 days, which is enough time to get the therapies made and delivered to patients.
The BMS trial is testing the experimental therapy in patients with certain neuroendocrine tumors and is expected to wrap up in July 2025, according to the federal clinical trials database. It’s being conducted in Brazil, Canada, France, the Netherlands, Spain and the US.
Bristol Myers Squibb said it is working on setting up a GMP manufacturing facility in Indiana that could eventually produce the actinium-225 isotope, but for now, it relies on third-party suppliers. The company expects the Indiana plant to be up and running in the first quarter of 2025. The company said Sunday it expects to restart new patient enrollment in the clinical trial in the third quarter.
In filings in November, RayzeBio said it experienced a “slight delay” with getting Ac225 at the beginning of the Russia-Ukraine war but “subsequently resolved” the issue. However, it still cautioned investors about the lack of alternative suppliers and supply guarantees.
Growing pains
Umar Mahmood, chief of nuclear medicine and molecular imaging at Massachusetts General Hospital in Boston, described the actinium supply constraints as “growing pains.” He noted that the field has faced shortages of isotopes of gallium, technetium and lutetium.
“All of a sudden, you have a market for buying up the actinium supply,” he said. “There’s a lot of jumping on the bandwagon. A lot of people are going, ‘Well, we should do actinium because actinium is leading to all these very high valuations and acquisitions.’”
Mahmood is not involved with the BMS studies.
There are a limited number of companies and governments currently supplying actinium-225 around the globe. In the US, the Energy Department has been a primary supplier of actinium for early-stage studies.
Fusion Pharmaceuticals, which is developing a prostate cancer treatment, said in March that it is relying on the Department of Energy to supply actinium for its studies in the US. AstraZeneca closed its $2.4 billion acquisition of Fusion on Tuesday.
In December, Fusion invested $20 million in radioisotope supplier Niowave to help it shore up its actinium production in return for a guaranteed percentage of its supply. RayzeBio also had a pact with Michigan-based Niowave as of July, according to a securities filing in which the SEC asked RayzeBio why the agreement was deleted from its prospectus disclosure. Niowave did not respond to requests for comment in time for publication.
Fusion has an additional agreement with Canadian supplier BWXT Medical for both actinium supply and generators.
“If you haven’t gotten in at this point and solidified either your supply agreements or whatever sort of agreements for actinium that you have, it’s going to be tough,” Fusion CTO Eric Burak said at an investor conference in March.
Other early-stage companies such as Abdera Therapeutics have signed several contracts with actinium suppliers. Abdera CEO Lori Lyons-Williams told Endpoints that the company checked in with its third-party suppliers this week after BMS paused its trial and confirmed that it has not experienced delays or issues with sourcing. The company is gearing up for its first clinical trial in the second half of this year.
The frenzy around radiopharmaceuticals has heightened demand for actinium-225, and more suppliers are planning to join the field. NorthStar Medical Radioisotopes is hoping to supply actinium-225 to pharmaceutical companies in 2025.
“We don’t classify this as a ‘shortage’ situation,” said NorthStar CEO Frank Scholz. “Instead, we believe the current situation with the BMS trial is evidence of an issue critical to the broader radiopharmaceutical sector — a misalignment between available Ac-225 and growing patient need and demand.”
Anna Brown contributed to reporting this article.