ESMO 2025 preview – Sanofi’s lead shot gets a boost

Sanofi, which last year licensed a lead-212-based radioconjugate, Alphamedix, from Orano Med and RadioMedix for €100m, apparently has reason to be cheerful about the deal, with the companies touting a phase 2 win on Wednesday.

Alphamedix an SSTR-targeted project, had already produced promising results from the Alphamedix-02 trial in gastroenteropancreatic neuroendocrine tumours (GEP-NETs), in radioligand-naive patients; now the companies are also claiming a win in a cohort of radioligand-experienced patients.

The partners aren’t giving any numbers for now, only saying that overall response rates, the primary endpoint, were “clinically meaningful”, and that benefits were also seen on progression-free and overall survival. Investors won’t have long to wait for the details – data are set to be presented at the upcoming ESMO conference.

The companies also plan to discuss the results with regulators, but didn’t say whether they expect to file based on an uncontrolled phase 2 trial and, if so, when this might happen.

Better than Lutathera?

An SSTR-targeting radioconjugate, Novartis’s Lutathera, is already approved for GEP-NETs, but produced a 13% ORR in its second-line Netter-1 trial, so there’s plenty of room for improvement. Lutathera uses lutetium-177, a beta-emitting payload, while alpha emitters like lead-212 are thought to be more potent and precise.

Still, lead-212 isn’t directly an alpha emitter; rather, it emits a beta particle to become bismuth-212, some of which then decays with the emission of an alpha particle.

Either way, early data have suggested that this approach might result in better efficacy than Lutathera.

Initial data from the Alphamedix-02 trial, which enrolled patients who had previously received somatostatin analogue therapy, were presented at ASCO 2024. In a 36 patient-strong radioligand-naive cohort, ORR was 56%.

The Alphamedix-02 trial of Alphamedix in SSTR+ve GEP-NETs

Source: Company release & ASCO 2024.

However, toxicity could be worth watching: 58% of patients had grade 3 or 4 adverse events, and 31% experienced serious adverse events. Three deaths were listed, two from progressive disease and one from sepsis, while a fourth death, from carcinoid syndrome, was mentioned in the abstract but missing from the ASCO presentation.

Long-term follow-up data in the radioligand-naive cohort will also be presented at ESMO.

One lead-212 rival is Perspective Therapeutics, which has struggled since its SSTR2-targeting project, 212Pb-VMT-α-NET, produced one objective response among nine neuroendocrine tumour patients in a phase 1/2 trial. More data on this asset are also due at ESMO.

ESMO will take place in Berlin on 17-21 October.