Novartis’ blockbuster radioligand therapy Pluvicto has cleared a key milestone on its quest to hit $5 billion in peak sales, securing a U.S. nod in an earlier form of prostate cancer that nearly doubles the number of patients that could benefit from the drug.
Late Friday, the FDA signed off on Pluvicto in tandem with an androgen receptor pathway inhibitor (ARPI) in patients with prostate-specific membrane antigen (PSMA)-positive metastatic hormone-sensitive prostate cancer (mHSPC).
Originally cleared as a post-chemotherapy treatment in PSMA-positive metastatic castration-resistant prostate cancer (mCRPC), Pluvicto moved up the treatment chain last March when the FDA endorsed the nuclear medicine in patients after therapy with an ARPI—a class that includes Pfizer and Astellas’ Xtandi—but before taxane-based chemo.
The new nod in mHSPC, meanwhile, represents Pluvicto’s first foray into an earlier manifestation of prostate cancer, which typically progresses to the castration-resistant form within 20 months, Novartis has said.
With the approval, Pluvicto can now be deployed across all stages of PSMA-positive metastatic prostate cancer, which Novartis says “nearly doubles” the pool of patients eligible for the radioligand med.
Worldwide, more than 186,000 men are diagnosed with mHSPC each year, per Novartis, which added that roughly a third of patients fail to achieve undetectable prostate-specific antigen levels with combinations of ARPI and androgen deprivation therapy (ADT) alone. The company noted that over 80% of prostate cancer patients present with the PSMA biomarker.
The FDA signed off on the drug after reviewing data from the late-stage PSMAddition trial, in which Pluvicto curbed the risk of disease progression or death by 28% in conjunction with standard of care (ARPI and ADT) versus standard of care alone. In a later updated analysis, the Pluvicto combo was shown to reduce the risk of progression or death by 33%, with Novartis flagging a positive overall survival (OS) trend favoring its drug.
Safety was on par with Pluvicto’s known profile. At the time of primary analysis, a little more than half of patients on Pluvicto reported grade 3 or greater adverse events versus 43% of those in the standard care control cohort.
"Patients with metastatic prostate cancer continue to face significant unmet need, underscoring the importance of introducing precision options earlier in the treatment journey,” Victor Bultó, Novartis U.S. president, said in a July 31 statement.
Novartis has pinned $5-billion peak sales hopes on Pluvicto—one of two radiopharmaceuticals that the Swiss pharma has managed to bring to market, alongside Lutathera in gastroenteropancreatic neuroendocrine tumors.
As a radioligand therapy (RLT), Pluvicto weds a targeting compound known as a ligand with the therapeutic radionuclide lutetium-177, which damages target cells.
Pluvicto is the poster child for the broader RLT class. While not the first, it has managed to succeed on the market in a manner validating a wave of more recent R&D efforts surrounding nuclear medicine for targeted cancer treatment.
The therapy faced a bit of a setback earlier this year, however, when Novartis withdrew an application with the European Medicines Agency for Pluvicto as a pre-chemotherapy treatment for PSMA-positive mCRPC, which Novartis CEO Vas Narasimhan credited at the time to “a different perspective on what is the appropriate comparator in this pre-taxane” setting.
Still, the impact of the withdrawal should be limited, according to Novartis, which explained earlier this year that it had not factored that European indication into its peak sales forecast to begin with.