Sanofi has announced that its radioligand therapy AlphaMedix (212Pb-dotamtate) achieved all primary efficacy endpoints in a Phase 2 study for gastroenteropancreatic neuroendocrine tumors (GEP-NETs), setting the stage for potential regulatory filings and marking a significant challenge to Novartis' leadership in the radioligand therapy market.
The mid-stage ALPHAMEDIX-02 trial, conducted in partnership with Orano Med and RadioMedix, demonstrated that the somatostatin receptor (SSTR)-directed radioligand therapy was effective in both treatment-naïve GEP-NET patients and those previously treated with Novartis' established therapy Lutathera (177-dotatate).
Clinical Trial Results Show Promise Across Patient Populations
The open-label study enrolled patients with unresectable or metastatic SSTR GEP-NET who had previously been treated with peptide receptor radionuclide therapy (PRRT) using Lutathera, as well as a PRRT-naïve group. While full data has not yet been released, Sanofi reported that AlphaMedix showed "clinically meaningful" overall response rates (ORR) and prolonged clinical benefits in both patient cohorts.
The therapy also demonstrated improvements in key secondary endpoints, including progression-free survival (PFS) and overall survival (OS), with what the companies described as a "manageable safety profile." Complete results are expected to be presented at the upcoming European Society for Medical Oncology (ESMO) Congress later this month.
Alpha-Emitting Technology Offers Potential Advantages
AlphaMedix distinguishes itself from existing treatments through its use of alpha particle emission rather than beta particles. This approach offers the potential to limit exposure of surrounding healthy tissue to radiation and reduce side effects compared to current therapies. The FDA recognized this potential by granting AlphaMedix breakthrough designation last year for both PRRT-exposed and PRRT-naïve GEP-NET patients.
"These data reinforce our belief that delivering highly potent alpha-emitters directly to cancer cells could potentially offer a meaningful new treatment option for people living with GEP-NETs," said Volker Wagner, chief medical officer at Orano Med.
Strategic Partnership and Market Positioning
Sanofi strengthened its position in radioligand therapy when it acquired a 16% stake in Orano Med, a subsidiary of French nuclear fuel company Orano, for €300 million ($325 million) in October 2023. This investment built upon an earlier three-way alliance for AlphaMedix development with RadioMedix.
The use of lead-212 (212Pb) as the isotope in AlphaMedix also provides a strategic advantage by potentially avoiding supply chain issues that affect companies developing other alpha emitters, such as actinium-225, which is favored by competitors including Novartis/Mariana Oncology, AstraZeneca, Bristol-Myers Squibb, and Bayer.
Competitive Landscape and Market Opportunity
The positive AlphaMedix results represent a direct challenge to Novartis' dominance in the radioligand therapy space. Lutathera, first approved for GEP-NETs in January 2018, generated net sales of $724 million in 2024, representing a 20% increase over the previous year. Novartis' broader radioligand portfolio, which includes the prostate cancer therapy Pluvicto with $1.4 billion in sales, has established the company as the current market leader.
However, competition is intensifying across the sector. ITM reported Phase 3 results with its 177Lu-based ITM-11 earlier this year and plans to file for approval in 2024, while Lantheus has developed a generic version of Lutathera.
GEP-NETs occur in the pancreas and other parts of the gastrointestinal tract from hormone-producing neuroendocrine cells. While these tumors are typically removed by surgery when possible, radioligand therapies have become a crucial second-line treatment option since Lutathera's approval, particularly for patients with limited options after initial treatment failure.
Wagner described the readout as representing "a pivotal movement for 212Pb-based platform," highlighting the potential broader implications for lead-212-based radioligand therapies beyond GEP-NETs.
The ALPHAMEDIX-02 data will form the basis of discussions with health authorities, though the companies have not provided specific details about regulatory filing timelines or geographic scope for potential submissions.
