Novartis China Achieves Milestone with Dual Indications Approval of First Radioligand Therapy Lutetium [177Lu] vipivotide tetraxetan for Advanced Prostate Cancer

In recent decades, the incidence and mortality of prostate cancer in China have continued to rise.^[1]. As the most common malignant tumor in the male urinary and reproductive system, prostate cancer poses a serious threat to male health. Moreover, compared with European and American countries,In China, prostate cancer patients are often diagnosed at a later stage, with a higher proportion of metastatic cases. At the initial diagnosis, 54% of patients have already developed metastases, and their prognosis is relatively poor.^[2]Endocrine therapy is the standard treatment for patients with advanced prostate cancer, but most patients with metastatic prostate cancer will still progress to mCRPC after 18-24 months of treatment.^[3]。

RLT enters the body through intravenous infusion,Targeted ligands recognize and bind to specific PSMA markers on the surface of prostate cancer cells. When circulating in the blood to the tumor site, the radiopharmaceutical (lutetium[¹⁷⁷Lu] enters the tumor cell along with the ligand, continuously releasing β-rays and causing DNA breaks., precisely targeting tumor lesions from "within." Notably, these radionuclides have concentrated energy and a short penetration distance (approximately 2 millimeters), enabling precise, efficient, and low-damage treatment goals.^[4]This mechanism of "targeted therapy" not only effectively eliminates cancer cells but also minimizes radiation toxicity to surrounding healthy tissues.

Lu[¹⁷⁷Lu] The approval of the first indication for tesixipide injection is based on the results of the global Phase III VISION study and the China bridging study. VISION is an international multicenter, randomized, open-label Phase III study.^[5], in PSMA-positive mCRPC patients whose disease progressed after prior treatment with ARPI and taxane-based chemotherapy, lutetium[¹⁷⁷Lu] Tixiviptide combined with SOC can significantly improve patients' radiographic progression-free survival (rPFS) and overall survival (OS).

The study results showed that, compared with the group using standard of care (SOC) alone (n=280),Lutetium [¹⁷⁷Lu] The risk of death in the terexiviptide group (n=551) was reduced by 38%.(OS 15.3 months vs. 11.3 months, HR 0.62, P<0.001),60% reduction in risk of disease progression or death(rPFS 8.7 months vs. 3.4 months, HR 0.40, P<0.001). In addition, the study also showed that lutetium[¹⁷⁷Lu] Tixiviptide in combination with SOC can effectively delay the decline in patients' quality of life, including:Time to Deterioration in Functional Assessment of Cancer Therapy - Prostate (FACT-P) Score(9.7 months vs. 2.4 months, HR 0.46),Delay to Brief Pain Inventory-Short Form (BPI-SF) Pain Intensity Worsening Time(14.3 months vs. 2.9 months, HR 0.45).

These results fully demonstrate that lutetium[¹⁷⁷Lu] Tixiviptide not only improves survival benefits but also significantly enhances the quality of life for patients, opening a new chapter in precise RLT for advanced prostate cancer treatment.

Given the potential negative impact of chemotherapy on quality of life, delaying or even avoiding its use has become an important direction in clinical practice. Statistics show that more than half of Chinese mCRPC patients do not receive docetaxel chemotherapy after the failure of first-line endocrine therapy.^[6]The PSMAfore study, as a randomized, multi-center, open-label Phase III trial, further confirmed the results of lutetium [¹⁷⁷Lu] The significant efficacy of teriparatide in mCRPC patients with disease progression after prior ARPI treatment but without chemotherapy, providing critical support for the drug's second approved indication.^[7]。

The results showed that, compared with the group switching to ARPI,Lutetium [¹⁷⁷Lu] Terixiptide group significantly prolonged the median rPFS of patients(11.60 months vs. 5.59 months, HR 0.49, 95% CI 0.39–0.61),Brings a higher PSA response rate（51% vs. 17%），PSA progression-free time extended to 10.64 months(vs. 4.24 months). Meanwhile, lutetium[¹⁷⁷Lu] Teseptide GroupThe objective response rate (ORR) reached 50% (vs. 15%), with 21% of patients achieving complete lesion remission (4% in the control group)., with a median follow-up time of 24.11 months, the median duration of response (DOR) was not reached [NE] vs. 10.05 months). Additionally, this therapy significantly prolonged the time to deterioration in FACT-P scores (9.17 months vs. 4.60 months) and BPI-SF scores (8.15 months vs. 4.50 months), with a lower incidence of symptomatic skeletal events (SSE) (13% vs. 29%). In terms of safety, compared to switching to ARPI, lutetium[¹⁷⁷Lu] The incidence of treatment-related adverse events ≥ Grade 3 was lower in the tesetrapib group (35.2% vs. 49.1%), most of which were reversible and rapidly recoverable, with good overall tolerability and no impact on subsequent treatment.^[7]。

These results fully demonstrate that lutetium[¹⁷⁷Lu] Tesevipide not only significantly improves disease control and quality of life, but also demonstrates the clinical value of "better when used earlier," offering patients longer and higher-quality survival hope.

The value of scientific research and innovation lies in benefiting more patients. Each achievement in research represents a small step forward in treatment options, but a giant leap of new hope for a patient.

RLT is not only a scientific innovation but also an embodiment of the "patient-centered" concept. Novartis is accelerating the full-chain layout from R&D to production, from clinical research to application. It strategically deploys RLT production bases worldwide to ensure the efficient coordination of drug supply and service systems, allowing innovative therapies to benefit patients in China faster, more steadily, and more broadly.

References:

[1] GLOBOCAN 2022. http://gco.iarc.fr/today/fact-sheets-cancers.

[2] National Health Commission of the People's Republic of China, et al. Guidelines for Diagnosis and Treatment of Prostate Cancer (2022 Edition).

[3] Huang Jian, Zhang Xu. Guidelines for the Diagnosis and Treatment of Urology and Andrology Diseases in China [M]. Beijing: Science Press, 2022.

[4] Nitipir C, Niculae D, Orlov C et al. Update on radionuclide therapy in oncology (Review). Oncol Lett. 2017; 14: 7011-7015.

[5] Sartor O, de Bono J, Chi KN, et al. Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med,2021,385:1091-1103.

[6] He D, Sun Z, Guo J, et al. A multicenter observational study of the real-world use of docetaxel for metastatic castration-resistant prostate cancer in China[J]. Asia Pac J Clin Oncol,2019,15:144-150.

[7] Morris, Michael J, Daniel C, Ken H,et al. 177Lu-PSMA-617 versus a change of androgen receptor pathway inhibitor therapy for taxane-naive patients with progressive metastatic castration-resistant prostate cancer (PSMAfore): a phase 3, randomised, controlled trial. The Lancet, Volume 404, Issue 10459, 1227 - 1239.