- The approval of the new indication will be in line with Pluvicto®The patient population for the treatment condition has expanded by approximately three times – for use in mCRPC patients who have not undergone chemotherapy after treatment with an androgen receptor pathway inhibitor (ARPI).
- In the global Phase III PSMAfore clinical study, compared to switching ARPI regimens, Pluvicto®Can significantly reduce the risk of disease progression or death by 59%, and extend the median radiographic progression-free survival (rPFS) to more than twice as long.
- In the real world, about half of mCRPC patients cannot receive second-line treatment due to insufficient survival time. It is very necessary to use effective and well-tolerated therapies early on.1
- Multiple radioligand therapy (RLT) production bases in the United States are fully capable of meeting the supply demand after the expansion of indications, and their industry-leading infrastructure can accelerate the delivery of radioligand therapy to patients.
Novartis recently announced that the U.S. Food and Drug Administration (FDA) has approved Pluvicto.®(lutetium Lu 177 vipivotide tetraxetan) is used for patients with metastatic castration-resistant prostate cancer (mCRPC) who are positive for prostate-specific membrane antigen (PSMA), have been treated with an androgen receptor pathway inhibitor (ARPI), and are considered suitable for delayed chemotherapy.
This indication was approved based on the results of the Phase III PSMAfore clinical study, which aligns with Pluvicto®The patient population for treatment conditions expanded by approximately three times. Research results show that, compared to switching ARPI regimens, Pluvicto®Reduced the risk of radiographic progression or death by 59% (HR=0.41; 95% CI: 0.29-0.56; p<0.0001) in PSMA-positive mCRPC patients. In an updated exploratory analysis, Pluvicto®The median imaging-based progression-free survival in the group more than doubled (11.6 months vs. 5.6 months)*.
“Pluvicto®The early use may revolutionize the treatment paradigm for mCRPC patients. Compared to switching to a second ARPI, it offers a more effective targeted therapy to delay disease progression."Michael Morris, M.D., Principal Investigator in the U.S. and Chief of the Prostate Cancer Section in the Genitourinary Oncology Service at Memorial Sloan Kettering Cancer Center, stated"The approval of this indication is an extremely important advancement, opening up a treatment option with clear clinical benefits for mCRPC patients who have received one ARPI treatment but have not undergone chemotherapy."
In the PSMAfore study, the final overall survival (OS) analysis numerically favored Pluvicto.®Group, the hazard ratio was HR=0.91 (95% CI: 0.72-1.14), with no statistical significance. This hazard ratio result was influenced by a high proportion of patients (60.3%) in the control group crossing over to Pluvicto.®The treatment group was affected. After adjustment for crossover, the hazard ratio for overall survival (OS) calculated using the inverse probability of censoring weighting (IPCW) method was 0.59 (95% CI: 0.38-0.91)**.
Other results from the PSMAfore study show that Pluvicto®Demonstrated consistent and better safety profiles. The most common adverse events of all grades were mainly grade 1-2, including dry mouth (61%), fatigue (53%), nausea (32%), and constipation (22%). Pluvicto®Without affecting the patient's ability to receive subsequent chemotherapy.
"PSMA-Targeted Radioligand Therapy Clinical Development Provides Important Direction for mCRPC Treatment."Dr. Oliver Sartor, Chair of the Genitourinary Oncology Disease Group at Mayo Clinic and Director of Radiopharmaceutical Clinical Trials, stated"Clinical trial data show that Pluvicto® can provide eligible patients with a clear clinical benefit in delaying disease progression, offering a new treatment option for such patients."
More than 35,000 men die from prostate cancer each year in the United States, and the incidence rate continues to rise.2About half of mCRPC patients are unable to receive second-line treatment due to insufficient survival time.1Although hormone therapy and chemotherapy are important treatment options for mCRPC, they are not suitable for all patients.3Many patients and doctors tend to avoid or delay chemotherapy due to side effects, and guidelines recommend avoiding the consecutive use of multiple ARPIs.4-7。
"As the number of treatment lines increases, the prognosis of these patients with metastatic prostate cancer continues to deteriorate, and they have long faced limited options and uncertain treatment outcomes."Gina Carithers, CEO and President of the Prostate Cancer Foundation, stated8，“Pluvicto®The expansion of indications brings more possibilities to the prostate cancer patient population and offers more options for patients in the early stages of treatment, enabling them to work with oncologists or urologists to develop the best treatment plan based on their individual needs."
"This time, Pluvicto®The expansion of indications provides nearly three times more patients with additional options, further establishing radioligand therapy as a cornerstone in cancer treatment."Novartis US President Victor Bultó stated"As a pioneer in the RLT field, Novartis is committed to providing education, resources, and practical solutions to healthcare professionals, ensuring that all patients have access to treatment in this severe disease."
About Pluvicto®（lutetium Lu 177 vipivotide tetraxetan）
Pluvicto®It is a radioligand therapy (RLT) administered intravenously, consisting of a targeting ligand combined with a therapeutic radionuclide (lutetium-177). After entering the bloodstream, Pluvicto®Can specifically bind to prostate cancer cells expressing PSMA. After binding, the energy released by the radioactive isotope can destroy the target cells, inhibit their replication ability, and/or induce tumor cell death.
Based on two Phase III studies, Pluvicto®Is currently the only PSMA-targeted drug that significantly improves rPFS and demonstrates good safety in ARPI-treated PSMA-positive mCRPC patients, regardless of whether they have received taxane treatment. Based on the approval of the U.S. Food and Drug Administration (FDA), Pluvicto®It is currently the first and only PSMA-positive mCRPC-targeted RLT that can be used before chemotherapy.
Novartis is exploring Pluvicto®Applications in earlier stages of the disease, including metastatic hormone-sensitive prostate cancer (PSMAddition, NCT04720157) and oligometastatic prostate cancer (PSMA-DC, NCT05939414).
Novartis and Radioligand Therapy (RLT)
Novartis is reshaping the treatment landscape for advanced cancer through Radioligand Therapy (RLT). By directly and precisely delivering therapeutic radiation energy to targeted tumor cells in any part of the body, it is used for the treatment of advanced cancer.
Novartis is developing a broad portfolio of RLT products, exploring new isotopes, ligands, and combination therapies to expand indications beyond gastrointestinal pancreatic neuroendocrine tumors (GEP-NETs) and prostate cancer to include breast cancer, colorectal cancer, lung cancer, and pancreatic cancer. Novartis has established a specialized global supply chain and production network, including advanced manufacturing sites in Millburn, New Jersey, Zaragoza, Spain, Ivrea, Italy, and Indianapolis, Indiana. The new manufacturing site in Carlsbad, California, will serve as the third RLT production facility in the United States, supporting the widespread application of RLT, strengthening the production network, and optimizing drug supply for patients on the West Coast.
Disclaimer
This press release contains forward-looking statements that are defined by the U.S. Private Securities Litigation Reform Act of 1995. Forward-looking statements can generally be identified by words such as “potential,” “can,” “will,” “plan,” “may,” “could,” “would,” “expect,” “anticipate,” “look forward,” “believe,” “committed,” “launch,” “target,” “outcome,” or similar terms, or by express or implied discussions regarding potential marketing approvals, new indications for Pluvicto, or regarding Pluvicto’s future potential revenues. You should not place undue reliance on these statements. Such forward-looking statements are based on our current expectations regarding future events and are subject to significant known and unknown risks and uncertainties. If one or more of these risks or uncertainties materialize, or if the assumptions underlying the forward-looking statements prove incorrect, actual results may differ materially from those described in the forward-looking statements. We cannot guarantee that Pluvicto will be submitted for approval or approved for sale in any market, or that it will gain any additional indications, or that it will be approved within a specified timeframe, nor can we guarantee its commercial success in the future. In particular, our expectations regarding Pluvicto could be affected by, among other things: inherent uncertainties in the research and development process, including clinical trial results and further analysis of existing clinical data; regulatory actions or delays or government regulation generally; global trends toward healthcare cost containment, including government, payor and general public pricing and reimbursement pressures, as well as requirements for increased pricing transparency; our ability to obtain or maintain proprietary intellectual property protection; specific prescribing preferences of physicians and patients; general political, economic and business conditions, including the effects of and efforts to mitigate pandemic impacts; safety, quality, data integrity or manufacturing issues; potential or actual data security and data privacy breaches, or disruptions of our information technology systems; and other risks and factors referred to in Novartis AG’s current Form 20-F on file with the US Securities and Exchange Commission. Novartis provides this press release as of the date hereof and does not undertake any obligation to update any forward-looking statements contained herein as a result of new information, future events or otherwise.
Disclosure: Dr. Sartor was involved in the clinical trial design and served as the chair of the trial steering committee. Dr. Sartor is a paid consultant for Novartis, with fees paid directly to the Mayo Clinic.
* Results observed in the third interim analysis of PSMAfore (NCT04689828) (data cutoff date: February 2024). Pluvicto®In the primary analysis (data cutoff date: October 2022), the centrally confirmed rPFS event was reached as the primary endpoint result.
* *IPCW is a well-established statistical method that requires multiple assumptions.
Statement
1. This press release aims to convey cutting-edge pharmaceutical information and research progress, not for advertising purposes.
2.The product Pluvicto® mentioned in this press release has not yet been approved in China.
3.The information contained in this press release is for reference only. Please follow the advice or guidance of doctors or other healthcare professionals.