Novartis Receives FDA Breakthrough Therapy Designation for 177Lu-PSMA-617 in Metastatic Castration-Resistant Prostate Cancer

Prostate Cancer (Image source: hopkinsmedicine.org)

June 17, 2021 /BioValleyBIOON/ --Novartis(Novartis) recently announced that the U.S. Food and Drug Administration (FDA）has granted Breakthrough Therapy Designation (BTD) to its targeted radioligand therapy 177Lu-PSMA-617 for the treatment of metastatic castration-resistant prostate cancer (mCRPC).

177Lu-PSMA-617 is a radioligand therapy (RLT)., such therapies combine a targeted compound that binds to tumor-expressed biomarkers with a radioactive isotope, inducing DNA damage and inhibiting tumor growth and proliferation. This therapeutic approach can precisely deliver toTumorTargeted delivery of radiation to cells, while limiting damage to surrounding normal tissues.

Metastatic prostate cancer has a poor prognosis, with a 5-year survival rate of approximately 30%.FDABreakthrough Therapy Designation (BTD) was granted to 177Lu-PSMA-617 based on positive results from the pivotal Phase 3 VISION study. This international, prospective, randomized, open-label, multicenter study was conducted in 831 patients with PSMA-PET-positive metastatic castration-resistant prostate cancer (mCRPC) who had disease progression after prior treatment with taxanes and androgen receptor-directed therapies (ARDTs). The efficacy and safety of 177Lu-PSMA-617 (administered as an intravenous infusion of 7.4 GBq every 6 weeks for up to 6 cycles) in combination with best standard of care (SOC) were evaluated and compared with SOC alone.

The results showed that,The study met two primary endpoints., compared with the SOC treatment group, the 177Lu-PSMA-617 + SOC treatment group: (1)Overall survival significantly prolonged (median OS: 15.3 months vs. 11.3 months; p < 0.001)、38% reduction in mortality risk (HR=0.62; 95% CI: 0.52-0.74); (2)Significantly prolonged radiographic progression-free survival (median rPFS: 8.7 months vs. 3.4 months; p < 0.001)、a 60% reduction in the risk of radiographic progression or death (HR=0.40; 99.2% CI: 0.29-0.57)。

These data confirm the potential of 177Lu-PSMA-617 to improve clinical outcomes in patients with PSMA-positive mCRPC. Based on these study results,NovartisA marketing authorization application for 177Lu-PSMA-617 is planned for submission in the United States and the European Union in the second half of 2021. Currently, the company is also conducting two pivotal trials for the treatment of early metastatic prostate cancer (PSMAfore, PSMAddition), with the aim of advancing therapeutic intervention into earlier stages of the disease.

177Lu-PSMA-617 (Image source: embs.org)

Prostate cancer is a cancer that develops in the prostate, a small walnut-shaped gland located in the male pelvis. In castration-resistant prostate cancer (CRPC), tumors continue to show signs of growth despite hormone therapy that lowers testosterone levels, such as elevated prostate-specific antigen (PSA) levels. In metastatic CRPC (mCRPC),TumorThe cancer has metastasized to other parts of the body, such as adjacent organs or bone, and remains refractory to hormone therapy. The 5-year survival rate for patients with mCRPC is approximately 15%.

Despite advances in the treatment of prostate cancer, there remains a very high unmet medical need for new targeted treatment options in patients with mCRPC. More than 80% of prostate cancerTumorhighly expresses a phenotypic biomarker called prostate-specific membrane antigen (PSMA), making it a promisingDiagnosisTargets (imaged via positron emission tomography [PET] scanning) and therapeutic targets for radioligand therapy.

177Lu-PSMA-617 is a PSMA-targeted radioligand therapy developed for the treatment of metastatic castration-resistant prostate cancer (mCRPC). This drug is a precision cancer treatment that combines a targeting compound (ligand) with a therapeutic radioisotope (radionuclide). Following intravenous administration, 177Lu-PSMA-617 binds to prostate cancer cells expressing PSMA (a transmembrane protein), resulting in higher drug uptake in tumors compared to normal tissues. Once bound, radiation (beta particles) from the radioisotope damagesTumorcells, destroying their replicative capacity and/or triggering cell death. The radiation from radioisotopes acts only over a very short distance to limit damage to surrounding cells. (Bioon.com)

Original Source:Novartis receives FDA Breakthrough Therapy designation for investigational 177Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer (mCRPC)