Sanofi steps back from radioconjugates

Alpha-emitting radiopharmaceuticals have lost one of their would-be contenders after Sanofi quietly pulled the plug on AlphaMedix, thinning the competitive field around Novartis’s Lutathera.

The decision is striking. The lead-212-based, SSTR-targeting radioconjugate was licensed in 2024 from Orano Med and Radiomedix in a deal worth €100m upfront.

Following the transaction, the asset generated clinical data that prompted Sanofi to say in October that it was preparing to move the programme into a phase 3 trial in gastroenteropancreatic neuroendocrine tumours (GEP-NETs).

Just four months later, however, not only has the phase 3 trial failed to materialise, but Sanofi has opted to discontinue the programme entirely.

Safety concerns

At ESMO last October, AlphaMedix posted what appeared to be encouraging efficacy data from the Alphametix-02 trial, including a 57% confirmed response rate in radioligand-naive GEP-NET patients.

However, some safety concerns arose from that data owing to a high incidence of dysphagia, for which botox treatment didn’t always provide long-term relief, and some renal toxicities. Such issues might have contributed to Sanofi’s decision to walk away from the asset.

On Thursday analysts at B Riley also pointed to competitive considerations. In the post-radioligand setting AlphaMedix reported a 19% centrally confirmed response rate, which on a cross-trial basis was lower than Bristol Myers Squibb’s RYZ101, an anti-SSTR therapy that uses actinium-225 as the radioisotope.  

By comparison, RYZ101 reported a 29% confirmed response rate in the phase 1b Action-1 study, which is evaluating the radioconjugate in GEP-NET patients who have progressed following radioligand therapy.

In that study grade 3 treatment-related adverse events were seen in 29% of patients, with anaemia and decreased lymphocyte counts being the most common.

Sanofi, for its part, when asked about the recent rationalisation of its phase 2 portfolio during its fourth-quarter earnings call, responded that it would now rely at least quarterly on "artificial intelligence-driven assessments to reallocate resources", acknowledging that this approach would result in some programmes being stopped.

With AlphaMedix off the board, Perspective Therapeutics could benefit, given that it's developing a similarly acting radioconjugate that also uses lead-212. That said, Perspective has encountered problems of its own.

In a phase 1/2 trial, 212Pb-VMT-α-NET showed a 35% response rate in radioligand-naive patients, a result that on a cross-trial basis was lower than what AlpheMedix achieved, though it was higher than the 13% ORR delivered by Lutathera in the Netter-1 trial. Perspective's stock climbed 66% on Thursday, but fell back 11% on Friday.