Novartis Announces Phase III Success of Radioligand Therapy 177Lu-PSMA-617 in Metastatic Castration-Resistant Prostate Cancer

On March 23, Novartis announced that its potential first-in-class targeted radioligand therapy (RLT), 177Lu-PSMA-617, met both primary endpoints in a Phase 3 clinical trial involving patients with advanced prostate cancer. Compared with the best standard of care, 177Lu-PSMA-617 significantly improved overall survival (OS) and radiographic progression-free survival (rPFS) in patients with metastatic castration-resistant prostate cancer (mCRPC). Novartis expects to submit regulatory applications in the United States and the European Union this year.

Prostate cancer is the second most common type of tumor in men worldwide. Over the past decade, the incidence of prostate cancer in China has been on the rise, and it has now become the fifth most common cancer among Chinese men. mCRPC is a severe form of prostate cancer in which the cancer has spread to other parts of the body, and tumors continue to proliferate even when androgen levels in the body are reduced to very low levels. The 5-year survival rate for patients with mCRPC is approximately 15%, and their treatment options are limited, representing a significant unmet medical need.

Radioligand therapy couples radioisotopes with molecules that bind to specific biomarkers expressed by tumors. It is one of the key technology platforms under development by Novartis, standing alongside targeted therapy, immunotherapy, and cell and gene therapy as the four major technological pillars of Novartis’ oncology drug development. Novartis has long been established in this field, with more than 15 R&D projects in its pipeline dedicated to developing next-generation radioligand anticancer therapies. The company previously acquired Advanced Accelerator Applications, a developer of radiopharmaceuticals, along with its FDA-approved peptide receptor radionuclide therapy, Lutathera. Recently, Novartis invested in Aktis Oncology, a startup focused on developing alpha particle-based radiotherapies.

Historically, radiation therapy for cancer has primarily relied on external beam radiation delivery. In contrast, radioligand therapy involves administering drugs carrying radioactive isotopes into the patient’s body, where they specifically bind to biomarkers expressed by tumors, thereby locally releasing radiation energy to destroy tumor cells.

177Lu-PSMA-617 is a candidate radioligand therapy acquired by Novartis in 2018 through its $2.1 billion acquisition of Endocyte. It combines lutetium-177 (177Lu) with a targeting agent that binds to prostate-specific membrane antigen (PSMA). PSMA is highly expressed in more than 80% of prostate cancers, making it a promising therapeutic target. The radiation emitted by 177Lu-PSMA-617 acts only over a very short distance, thereby limiting damage to surrounding healthy cells.

In the randomized, open-label, phase 3 VISION trial, patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) received treatment with either 177Lu-PSMA-617 or best standard of care. These patients had previously been treated with taxanes or androgen receptor–targeted therapies but experienced disease progression. The trial results demonstrated that 177Lu-PSMA-617 met both primary endpoints, significantly improving overall survival and radiographic progression-free survival. Specific data will be presented at an upcoming medical conference.

“The five-year survival rate for patients with mCRPC is less than one in six, highlighting an urgent need for new treatment options. These breakthrough data demonstrate the potential of 177Lu-PSMA-617, and we plan to submit them to regulatory authorities as soon as possible,” said Dr. John Tsai, Chief Medical Officer and Head of Global Drug Development at Novartis.

References:

[1] Novartis announces positive result of phase III studywith radioligand therapy 177Lu-PSMA-617 in patients with advanced prostatecancer. Retrieved March 23, 2021, from https://www.novartis.com/news/media-releases/novartis-announces-positive-result-phase-iii-study-radioligand-therapy-177lu-psma-617-patients-advanced-prostate-cancer

[2] Novartis Oncology Pipeline Update. Retrieved March 23,2021, from https://www.novartis.com/sites/www.novartis.com/files/2020-06-novartis-oncology-pipeline-update-presentation.pdf

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