The radioisotope lutetium-177 is at risk of slipping into shortage due to rapidly increasing demand, outdated manufacturing infrastructure and vulnerable supply chains, some radiopharma manufacturer and isotope supplier executives told Endpoints News.
Demand for Lu-177 has skyrocketed because of high interest in radiopharmaceuticals in cancer treatment, ITM CEO Steffen Schuster said. According to Schuster, Germany-based ITM is one of the largest global suppliers of Lu-177. Evaluate predicts the radiopharma market will be a $7 billion opportunity by 2030.
Steffen SchusterA spokesperson for Novartis — the only company with an approved Lu-177 radiopharma product, and which has previously faced supply constraints for its lutetium-based therapies — reiterated it is not experiencing isotope shortages now and has “sufficient” supply for its clinical and commercial radiotherapy portfolios.
Novartis has four radiotherapy manufacturing sites and an “unconstrained” supply of radioisotopes to meet current and future demand, the spokesperson added.
Isotope supply challenges have hit the headlines in recent weeks, with the shortage of actinium-225 causing Bristol Myers Squibb to pause a Phase 3 trial. Lu-177 is even more in-demand as it is a core radioisotope in many products in the clinic, and one of the isotopes in approved therapeutic products.
The demand for isotopes will become “unlike anything we’ve seen before,” even if only 10% of the radiotherapies in clinical trials get approved, said SpectronRx CEO John Zehner. SpectronRx is a radiopharma CDMO and a Lu-177 isotope supplier.
There are around 305 clinical trials involving Lu-177-labeled treatments, according to Citeline. Of these, 155 are ongoing and 35 are active Lu-177 programs in development. GlobalData said there are at least 13 Phase 3 trials investigating the isotope and 57 in Phase 2.
John ZehnerTelix Pharmaceuticals, Lantheus, Curium Pharma and ITM have Lu-177 assets in Phase 3. A Lantheus spokesperson said it monitors supply of radioisotopes closely, given the just-in-time nature of radiopharmaceutical supply chains. Australian company Telix Pharma declined to comment because it is currently looking to list on the Nasdaq, while Curium did not reply to Endpoints’ requests for comment.
Novartis’ Lutathera was approved in 2018, and Pluvicto entered the market in 2022. Lutathera made $169 million in the first quarter of this year, up 14% compared to the same time last year. Meanwhile, Pluvicto sales grew in the first quarter of this year to $310 million, up by 47% compared to the same period last year.
Old equipment
Another reason for the risk of an Lu-177 shortage is that radioisotope companies are using outdated and old equipment, AtomVie CEO Bruno Paquin said. Most reactors making isotopes are around 45 to 65 years old, which is near the end of their “useful life,” he added.
Old equipment is sensitive to maintenance shutdowns — planned or unplanned — leading to production delays, Paquin said. AtomVie is a radiopharma manufacturer that works on Lu-177.
Bruno PaquinGeopolitical tensions also threaten Lu-177 supply chains.
Russia remains the predominant supplier of stable isotopes, including Lu-177, Paquin said. Some time before being acquired by Bristol Myers, RayzeBio warned its investors of a potential Ac-225 shortage due to its reliance on a supplier in Russia. The Lantheus spokesperson added it has ensured its partners source their Lu-177 from multiple sources.
To address the shortage risk, there’s been an effort to increase domestic capacity, Zehner said. Lu-177 supply has scaled rapidly throughout the industry in the past few years, which is a reflection of new equipment installations to increase output, the Lantheus spokesperson said, adding that Lu-177 manufacturing infrastructure is largely based on new equipment.
Paris-headquartered Curium said last week it is adding a new high-flux reactor in France to improve its supply of Lu-177 to benefit patients over the next five years. Telix Pharma acquired Texas-based IsoTherapeutics in February to boost in-house capacity for isotope processing and radiopharma manufacturing.
Novartis received the FDA go-ahead to make Pluvicto at a site in Indianapolis in January this year. “We are dedicating significant resources to bolster our [radioligand therapy] manufacturing and supply chain for the future,” the Novartis spokesperson added.
ITM is also “confident” in its own capacity to supply Lu-177, Schuster said. Last week, the company announced its $188 million budget to help boost in-house manufacturing of Lu-177. “Our job is to do the best we can to address these complexities and maintain supply,” Schuster said.
Editor’s note: This article was updated to clarify that not all approved radiotherapies use Lu-177.