Novartis' Next Billion-Dollar Radiopharmaceutical Lutathera Advances in China with IND Approval

On February 9, 2025, according to the public information from the Center for Drug Evaluation of the National Medical Products Administration, the clinical trial applications for Lutathera (lutetium [177Lu] oxodotreotide injection) and 68Ga-PSMA-11 (gallium [68Ga] oxodotreotide injection kit), both developed by Novartis, were accepted for public review by the Center for Drug Evaluation of the National Medical Products Administration.

According to the Novartis annual report, in 2024 Lutathera entered Novartis' top 20 brands with global net sales reaching $724 million. Sales are expected to increase further in 2025, and it is anticipated to become the next billion-dollar radiopharmaceutical following Pluvicto (177Lu-PSMA-617, with sales of $1.392 billion in 2024).

Novartis has a forward-looking vision in the layout of the nuclear medicine track.

Lutathera was the main product obtained through the establishment of a radiopharmaceutical technology platform, after Novartis acquired the French company Advanced Accelerator Applications (AAA) for $3.9 billion back in 2017.

Lutathera is the world's first PDC (Peptide-Drug Conjugate) drug. The structure of PDC is similar to that of ADC, with the difference lying in the targeting unit. The targeting unit of ADC is an antibody, while for PDC, it is a peptide. PDC mainly consists of three parts: a peptide, a linker, and a cytotoxin.

In addition, the mechanism of action of PDC is similar to that of ADC. It covalently links targeting peptides and cytotoxins through a cleavable linker within cells, precisely targeting specific receptors on tumor cells, controllably releasing cytotoxins, thereby killing tumor cells; while achieving highly efficient and precise treatment, it reduces damage to other tissues. By using different radionuclides, diagnostic or therapeutic effects can be achieved.

The uniqueness of Lutathera lies in its peptide molecule DOTA-TATE, which is conjugated with Lu-177 through a chelating agent to form a novel compound drug. After being injected into the human body, Lutathera utilizes receptor-ligand targeting recognition to capture tumor cells, thereby delivering the radiopharmaceutical into the tumor tissue. Lu-177 then emits high-energy beta rays to ultimately destroy the tumor cells.

In October 2017, Lutathera was approved for marketing by the European Medicines Agency (EMA), rewriting the treatment landscape for neuroendocrine tumors. In January 2018, Lutathera also successfully received FDA approval, becoming the first FDA-approved radioligand therapy for the treatment of adult patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs). These tumors are positive for somatostatin hormone receptors and include those of the foregut, midgut, and hindgut.

After officially entering the U.S. market, Lutathera's international influence continues to expand.

In 2021, Lutathera was approved for marketing in Japan. In 2024, the FDA approved Lutathera for the treatment of somatostatin receptor (SSTR)-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs) in pediatric patients aged 12 years and older, including foregut, midgut, and hindgut neuroendocrine tumors. Notably, this is the first time the FDA has approved a radiopharmaceutical for the treatment of SSTR-positive GEP-NETs in pediatric patients aged 12 years and older.

In recent years, RDC drugs have become a hot spot in nuclear medicine research and development due to their demonstrated therapeutic potential in the field of oncology and the promotion of Novartis' blockbuster drug Pluvicto.

For patients with advanced cancer, especially those with multiple metastases, RDC drugs offer a new treatment option. Moreover, RDC drugs can facilitate the integration of diagnostics and therapeutics (theranostics) — where the same targeting ligand and linker can be combined with either therapeutic or diagnostic imaging radionuclides. Each therapeutic drug can have a corresponding diagnostic agent, allowing patients to receive timely treatment following diagnosis, thus saving time and improving efficiency. For instance, Novartis' 68Ga-PSMA-11 and lutetium [177Lu]-vipivotide tetraxetan both target PSMA and are used for PET imaging and treatment of prostate cancer.

Among them, 68Ga-PSMA-11 was approved by the FDA in December 2020, becoming the first drug for positron emission tomography (PET) imaging of prostate-specific membrane antigen (PSMA)-positive lesions.

68Ga-PSMA-11 is a radioactive diagnostic agent suitable for patients suspected of having metastatic prostate cancer, as well as for patients suspected of prostate cancer recurrence based on elevated serum prostate-specific antigen (PSA) levels. 68Ga-PSMA-11 is administered intravenously, and once injected, it binds to PSMA and indicates PSMA-positive prostate lesions in body tissues through PET imaging.

Not long ago, on February 6, 2025, according to the CDE official website, the clinical trial application for [225Ac]Ac-PSMA-617 Injection submitted by Novartis was accepted (Acceptance No.: JXHL2500015). [225Ac]Ac-PSMA-617 (AAA817) is an RDC drug targeting PSMA, indicated for prostate cancer.

However, unlike the two approved products mentioned above, the FDA has not yet approved any radiopharmaceuticals based on the Ac-225 radionuclide. Not only Novartis, but any MNC involved in this field could potentially emerge as the ultimate winner.

In China, no original or similar products have been approved for marketing. However, some companies have also joined the research and development wave of Lutetium [177Lu] oxodotreotide.

Xiantong Pharmaceutical is one of the leading companies, with its self-developed Lutetium [177Lu] oxodotreotide injection making smooth progress. It has successfully completed the Phase III clinical study "for the treatment of unresectable or metastatic, progressive, well-differentiated (G1 and G2) adult gastroenteropancreatic neuroendocrine tumors (GEP-NETs) that are somatostatin receptor-positive," and has already completed the enrollment of 196 patients.

In addition, Lutetium [177Lu] Oxodotreotide Injection developed by Tianjin Hengrui, a subsidiary of Hengrui Medicine, was approved by the NMPA for clinical trials in 2023. This not only fills the gap in Hengrui's oncology pipeline for radionuclide precision therapy but also enriches its product portfolio.

In the same year, the generic drug Lutetium [177Lu] Oxodotreotide Injection developed by Atom High-Tech also received the "Drug Clinical Trial Approval Notice" issued by the NMPA. It was approved to conduct clinical trials for the treatment of unresectable or metastatic, progressive, well-differentiated (G1 and G2), and somatostatin receptor-positive adult gastroenteropancreatic neuroendocrine tumors (GEP-NETs). This became another significant progress in the registration of radiopharmaceuticals following the company's therapeutic capsule.

In terms of integrated diagnosis and treatment, Yantai Lancheng Bio, a subsidiary controlled by Dongcheng Pharmaceutical, has developed a diagnostic drug targeting FAP, Fluorine [18F] Fibrostatin Injection, which was approved for clinical use in China at the end of 2022 based on the concept of integrated diagnosis and treatment. In addition, its therapeutic drug targeting FAP, 177Lu-LNC1004, obtained clinical approval in the United States, Singapore, and China in 2023, and was recently granted Fast Track designation by the FDA. Meanwhile, Fabuxin Tian also has a diagnostic drug targeting FAP, Technetium [99mTc]-H7ND, currently in the clinical stage.

Back to Novartis, through acquisitions, it has rapidly built up a radioligand therapy technology platform. One of its two blockbuster products, Pluvicto, has become a billion-dollar molecule, while Lutathera is also showing great potential to become the next big hit. In the Chinese market, in addition to the aforementioned players, China Isotope & Radiation Corporation, Fulllink Pharmaceuticals, and HenePharm have also joined the fray, making the market extremely vibrant.

As Novartis' three nuclear medicine products have been approved for IND in China, domestic companies such as China Isotope & Radiation Corporation and Dongcheng Pharmaceutical will face greater competitive pressure, and the research and development process of domestic nuclear medicine products will further accelerate. However, this also means that upstream isotope production, midstream drug research and development and production, and downstream clinical applications will form a closer collaborative relationship, promoting the coordinated development of the entire industry chain and providing more treatment options for cancer patients in China.

References:

Nuclear Medicine News | Novartis' Original Lutetium [177Lu] Oxodotreotide Injection Enters the Chinese Market

Atomic High-Tech Lutetium [177Lu] Oxodotereotide Injection Approved for Clinical Use in Gastrointestinal and Pancreatic Neuroendocrine Tumors