Sanofi Doubles Down on Radiopharmaceuticals with €5.2 Billion Combined Investment in AlphaMedix and Orano Med

Yesterday (October 17), Sanofi announced that Sanofi and Orano Med (a subsidiary of Orano Group) have reached an agreement to combine their expertise in combating rare cancers, further accelerating the development of next-generation Radioligand Therapy (RLT).

According to the agreement, Sanofi and Orano will jointly invest in a new entity operating under the Orano Med brand, focusing on the discovery, design, and clinical development of next-generation radioligand therapies (RLT) based on the alpha-emitting isotope lead-212 (212Pb). Sanofi will make an equity investment of 300 million euros (approximately 2.313 billion yuan), holding about 16% of the new entity, Orano Med, with a valuation of 1.9 billion euros (approximately 14.648 billion yuan).

At the beginning of last month, Sanofi announced that it had reached a licensing agreement with RadioMedix and Orano Med for RLT, focusing on RadioMedix's AlphaMedix™, an RLT therapy developed for rare cancers.²¹²Pb-DOTAMTATE). According to the agreement, Sanofi will pay RadioMedix and Orano Med an upfront payment of 100 million euros and sales milestone fees of up to 220 million euros (totaling 320 million euros, approximately 2.5 billion RMB), as well as tiered royalties. After the partnership is established, Sanofi will be responsible for the global commercialization of the project, and Orano Med will handle the production of AlphaMedix™ through its global industrial platform.

Looking at the various sub-tracks in the biopharmaceutical industry, radiopharmaceuticals are gradually becoming a battleground for global pharmaceutical giants. In addition to Sanofi, multinational pharmaceutical companies such as Novartis, Bayer, AstraZeneca (AZ), Bristol-Myers Squibb (BMS), and Eli Lilly have also made moves to secure a favorable position in this innovative therapy track.

The collaboration with RadioMedix and Orano Med marks Sanofi's first foray into the radiopharmaceuticals sector. Despite Sanofi’s R&D head Houman Ashrafian stating during the Q2 earnings call that the company currently has no radioactive therapy projects, mentioning, "We are being cautious in this area and considering truly differentiated therapeutic approaches," within just a month, Sanofi's determination to enter the radiopharmaceuticals field became evident through pipeline collaborations and additional equity investments.

The focus of this additional equity investment still revolves around AlphaMedix, a radiopharmaceutical currently in Phase II clinical trials.

AlphaMedix consists of a peptide complex targeting SSTR labeled with Pb-212, which acts as an in vivo generator of alpha particles. It is suitable for subjects with unresectable metastatic somatostatin receptor (SSTR)-positive neuroendocrine tumors (NET). The Pb-212 isotope is particularly suited for SSTR therapeutic applications due to its half-life, high energy, short decay path length, and irreversible damage to double-stranded DNA. This therapy received Orphan Drug Designation (ODD) from the FDA in 2018 and won the TechConnect Innovation Award in 2020.

In February this year, the FDA also granted AlphaMedix Breakthrough Therapy Designation (BTD) for the treatment of adults with unresectable or metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs) expressing somatostatin receptors who are eligible for peptide receptor radionuclide therapy (PRRT).

Its Breakthrough Therapy Designation is based on the results of Phase I and ongoing Phase II clinical trials, which evaluated the safety and efficacy of AlphaMedix. In the Phase I study, AlphaMedix was well-tolerated and significantly reduced tumor burden, with a durable response rate (according to RECIST 1.1, ORR) of 62.5%.

Currently, there is one therapeutic radiopharmaceutical targeting SSTR that has been approved for marketing globally, which is Novartis' Lutathera. Once AlphaMedix therapy is launched, it will quickly compete with Novartis' radiopharmaceutical, Lutathera.

Lutathera is a β-particle radiotherapy based on lutetium-177, which Novartis acquired in 2017 for $3.9 billion through the purchase of Advanced Accelerator Applications. As a peptide receptor radionuclide therapy (PRRT) drug, Lutathera can be used to treat gastroenteropancreatic neuroendocrine tumors (GEP-NETs) that are positive for somatostatin receptors (SSTR).

However, compared with β-particle radiopharmaceuticals, α-nuclide radiopharmaceuticals have unique advantages in tumor treatment. Specifically, α-nuclides emit α-particles during decay, and their linear energy transfer (LET) is nearly a hundred times higher than that of β-nuclides, resulting in significantly better tumor-killing effects. On the other hand, β-nuclides damage single-stranded DNA in tumor cells, which can be repaired, potentially leading to tumor recurrence. However, α-nuclides directly damage double-stranded DNA in tumor cells, causing permanent cell death, and are hailed as "radiation therapy with surgical precision."

In addition, clinical trial data also show that α nuclides can kill cancer cells and trigger tumor immune responses, which have a mutually reinforcing effect with immunotherapy, achieving a "one plus one greater than two" effect in tumor treatment. In terms of safety: the range of α nuclides is short, only a few cells, causing minimal damage to normal tissues and almost no side effects, thus offering higher safety.

This also means that, theoretically, AlphaMedix has potential high efficiency and selectivity in cancer treatment, which may make it more advantageous than β-particle therapy in certain situations. However, the specific efficacy still depends on subsequent clinical data.

AlphaMedix is the result of a collaboration between RadioMedix and Orano Med, with RadioMedix responsible for drug development and Orano Med taking on production responsibilities.

RadioMedix, founded in 2006, has collaborated with multiple pharmaceutical companies as a "nuclear medicine enabler" to develop various pipelines. This includes the company’s first diagnostic product, 64Cu DOTATATE (Detectnet), which received FDA approval in September 2020.^®) and AlphaMedix in collaboration with Orano Med, among others. In addition, RadioMedix is also developing analgesics for the treatment of brain tumors and pancreatic ductal adenocarcinoma (PDAC).

Orano Med, which has received equity investment this time, stands out the most due to its establishment of a Pb-212-based radioligand production facility in France at the beginning of 2024. By mid-year, it had also started construction of the world's first industrial-scale 212Pb radiopharmaceutical manufacturing plant in Brownsburg, near Indianapolis, Indiana, USA. By 2025, this will enable Orano Med to produce 10,000 doses annually on a global scale, with the goal of producing ten times that amount within a decade. Additionally, by being close to major domestic and international distribution networks, reliable transportation of radiopharmaceutical products is ensured. This more directly demonstrates Sanofi's ambition in the nuclear medicine sector.

On one hand, the raw materials of radioisotopes are facing a global shortage. Currently, isotopes are mainly produced through two methods: reactors and accelerators, with a large number of reactors concentrated in Europe and America. It is expected that by 2030, multiple active reactors worldwide will be shut down, leading to a tight supply of medical isotopes globally. The process of the global isotope shortage is arriving faster than anticipated.

On the other hand, limited by the half-life of radioactive isotopes, the drug's activity will decrease within a specific time period, thus requiring timely delivery and administration to patients. Due to the limited dosing time window, these drugs are typically produced in single-dose forms, taking into account transportation distance and cycle for drug delivery. This not only requires mature and complete upstream and downstream industries and radiopharmacy support but also demands the presence of medical institutions with qualifications for clinical use of nuclear medicine within a certain range.

Against this backdrop, even Novartis, known as the "leader in nuclear medicine," has faced capacity and supply chain issues. In the first half of 2023, the global production and supply of Pluvicto encountered problems, leading to distribution delays, drug shortages, patient treatment delays, and hindered promotion, resulting in a situation where patients were "waiting in line but unable to access the medication." It was not until the end of October that the FDA removed Pluvicto from the drug shortage list.

To address the imminent capacity issues, Novartis has accelerated the establishment of production bases over the past five years, including setting up radiopharmaceutical production facilities in Italy, Spain, the United States, and China. In January this year, the FDA approved Novartis' Indianapolis-based production site for the commercial production of Pluvicto, which is currently Novartis’ largest radiopharmaceutical production base, capable of reaching patients across the U.S. within 12 hours. CEO Vas Narasimhan stated that Novartis aims to deliver over 250,000 doses annually by 2024 through the construction of four facilities.

Previously, in September, when Sanofi announced its entry into the nuclear medicine field, according to the Pharmaceutical Economy News, industry insiders analyzed that, considering the upfront payment amount and its proportion at that time, it was not particularly high given that AlphaMedix was in Phase II clinical trials. This strategy also reflects Sanofi's cautious layout in the nuclear medicine field, as well as its rational assessment of the future commercial potential of the AlphaMedix project.

And now, for Sanofi, which aims to challenge Novartis' position in the nuclear medicine sector, increasing its equity investment in Orano Med not only indirectly addresses potential capacity and supply chain issues with AlphaMedix but also serves as an "insurance policy" for Sanofi in the nuclear medicine field — even if AlphaMedix is not entirely successful, Sanofi can still secure a foothold in nuclear medicine through indirect control of production bases.

Reference Article:

1. "Over 2.5 Billion, Major Nuclear Medicine Deal +1" VCBeat

2. "The First Foreign-Invested Nuclear Medicine Production Base Officially Begins Construction in Zhejiang!" VCBeat

3. The Nuclear Medicine Territory of MNC Giants! Novartis Leads, Sanofi Joins with 320 Million Euros, Bayer, AZ and Others in Hot Pursuit - Pharmaceutical Economy News