Novartis Submits NDA for 177Lu-PSMA-617 Following Landmark VISION Trial Demonstrating Significant Survival Benefits in Metastatic Castration-Resistant Prostate Cancer
Jun 30, 2021 23:56
CST Updated
23:56
Novartis
Drug Development and Manufacturing
Prostate cancer (Image source: hopkinsmedicine.org)
June 30, 2021 /BioonBIOON/ --Novartis(Novartis) recently announced that the results of the pivotal Phase 3 VISION study evaluating the targeted radioligand therapy 177Lu-PSMA-617 for the treatment of prostate cancer have been published in the *New England Journal of Medicine* (NEJM). The results showed that,In patients with progressive PSMA-positive metastatic castration-resistant prostate cancer (mCRPC), 177Lu-PSMA-617 in combination with standard of care (SOC) significantly improved overall survival (OS) and radiographic progression-free survival (rPFS) compared with SOC.For details, see the NEJM article:Lutetium-177–PSMA-617 for Metastatic Castration-Resistant Prostate Cancer。
177Lu-PSMA-617 is a radioligand therapy (RLT). This class of therapy combines a targeted compound capable of binding to tumor-expressed markers with a radioactive isotope, thereby inducing DNA damage and inhibiting tumor growth and replication.This treatment can preciselyTumorCell-targeted radiation delivery, while limiting damage to surrounding normal tissues.
Previously, the United StatesFDABreakthrough Therapy Designation (BTD) has been granted to 177Lu-PSMA-617 for the treatment of metastatic castration-resistant prostate cancer (mCRPC). The prognosis for metastatic prostate cancer is poor, with a 5-year survival rate of approximately 30%.
NovartisJeff Legos, Global Head of Oncology Development, stated: "We are proud of these data. In prostate cancer patients who have previously received multiple regimens and currently have limited treatment options, 177Lu-PSMA-617 can significantly shrinkTumor, extending the lives of prostate cancer patients. We believe that,As a radioligand therapy, 177Lu-PSMA-617 holds significant potential to improve the prognosis of advanced prostate cancer.. Currently, we have initiated two new Phase III studies for earlier-stage treatment.”
VISION was an international, prospective, randomized, open-label, multicenter study conducted in 831 patients with PSMA-PET-positive metastatic castration-resistant prostate cancer (mCRPC) who had disease progression following prior treatment with taxanes and androgen receptor-directed therapy (ARDT). The study evaluated the efficacy and safety of 177Lu-PSMA-617 (administered as a 7.4 GBq intravenous infusion every 6 weeks for up to 6 cycles) plus standard of care (SOC), compared with SOC alone.
The results showed that the study met the 2 primary endpoints; compared with the SOC treatment group, the 177Lu-PSMA-617 + SOC treatment group: (1)Significantly prolonged overall survival (median OS: 15.3 months vs. 11.3 months; p < 0.001) and a 38% reduction in the risk of death（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) and a 60% reduction in the risk of radiographic progression or death（HR=0.40；99.2%CI:0.29-0.57）。
Additionally, compared with the SOC treatment group, the 177Lu-PSMA-617 + SOC treatment group: (1)Time to first symptomatic skeletal event (SSE) or death was significantly delayed (median time: 11.5 months vs 6.8 months)；p＜0.001；α=0.05; HR=0.50[95%CI:0.40，0.62]）；（2）The overall response rate was significantly higher (ORR: 29.8% vs 1.7%; p < 0.001).
In terms of safety, 9.3% of patients in the 177Lu-PSMA-617 + SOC treatment group experienced serious drug-related treatment-emergent adverse events, compared with 2.4% in the SOC treatment group.
The above data confirm the potential of 177Lu-PSMA-617 to improve clinical outcomes in patients with PSMA-positive mCRPC. Based on these study results,NovartisPlans to submit a marketing application for 177Lu-PSMA-617 in the United States and the European Union in the second half of 2021.
177Lu-PSMA-617 (Image source: embs.org)
Prostate cancer is a cancer that occurs in the prostate, a small, walnut-shaped gland in the male pelvis. In castration-resistant prostate cancer (CRPC), despite testosterone-lowering hormone therapy, the tumor shows signs of growth, such as elevated prostate-specific antigen (PSA) levels. In metastatic CRPC (mCRPC),TumorIt has spread to other parts of the body, such as adjacent organs or bones, and remains unresponsive 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 therapies in patients with mCRPC. More than 80% of prostate cancer`Tumor`Highly expresses a phenotypic biomarker known as prostate-specific membrane antigen (PSMA), making it a promising# DiagnosisTargets (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 a higher uptake of the drug in tumors compared to normal tissues. Once bound, the radiation (beta particles) from the radioisotope damagesTumorcells, impairing their replicative capacity and/or triggering cell death. The radiation emitted by the radioisotope acts only over a very short distance to limit damage to surrounding cells.
Currently, Novartis is also conducting two additional clinical trials to evaluate 177Lu-PSMA-617 for earlier-line treatment of metastatic prostate cancer, including in pre-taxane mCRPC (PSMAfore) and metastatic hormone-sensitive prostate cancer (mHSPC) (PSMAddition). Furthermore,NovartisThe potential of 177Lu-PSMA-617 for early-stage treatment of prostate cancer is also being evaluated. (Bioon.com)