After much delay, Novartis has finally won a key FDA go-ahead for Pluvicto, opening up the radioligand therapy to a much broader prostate cancer population.
The new approval, which triples Pluvicto’s eligible patient population, allows the radiopharmaceutical to treat PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) before taxane-based chemotherapy, Novartis said Friday. Patients will have to have been treated with an androgen receptor pathway inhibitor (ARPI) to be considered.
Pre-chemo mCRPC represents the most important indication in Novartis’ plan for Pluvicto to achieve more than $5 billion in peak sales. Initially cleared by the FDA in 2022 in the post-chemo setting, Pluvicto’s revenue is currently annualizing at about $1.5 billion based on its most recent quarterly number.
“This approval is a significant step forward and should open the doorway to a therapy that has clear clinical advantages for the patient with mCRPC who has progressed on one ARPI and has not received chemotherapy,” Michael Morris, M.D., of Memorial Sloan Kettering Cancer Center, said in a statement Friday.
Morris led the phase 3 PSMAfore trial that supported Pluvicto’s pre-chemo approval.
But nothing worth having comes easy. In Novartis’ case, the PSMAfore trial met its primary endpoint in late 2022. Data presented the following year showed that, compared with a change in ARPI therapy, Pluvicto slashed the risk of progression or death by 59%. Patients who took the radioligand therapy went 9.3 months without disease progression, versus 5.6 months in the control group, according to the primary analysis.
But Novartis had to delay its FDA filing twice to collect more mature patient survival data. The Swiss pharma only started putting its application plan together after overall survival data turned in Pluvicto’s favor in the spring of 2024. Even after the submission, the FDA requested the flexibility to review the final overall survival of PSMAfore, which, luckily for Novartis, remained in Pluvicto’s favor.
The updated Pluvicto label now shows that it helped patients live a median 24.5 months, while those in the control group went 23.1 months. The death risk was 9% in favor of Pluvicto, although it was not statistically significant.
Notably, 60% of patients who were randomized to the comparator arm crossed over to receive Pluvicto after disease progression. After adjusting for the crossovers, Pluvicto was linked to a 41% reduction in the risk of death, according to Novartis.
As Novartis waited for this major expansion opportunity, the company has been busy expanding its manufacturing capacity. After several investments, including winning an FDA go-ahead for an Indianapolis plant to supply commercial Pluvicto, Novartis said Friday that its multiple U.S. facilities can fully meet the demand that comes with the earlier-line approval.
Outside the U.S., the Swiss pharma is also building radioligand therapy production sites in Japan and China.
Besides manufacturing capacity, expanding access in the community setting would be another important factor that will determine Pluvicto’s longer-term growth potential. The radioactive treatment is currently available only through designated treatment centers, which are mainly large hospitals or academic facilities. The company had more than 590 sites opened for Pluvicto, including 350 sites that were actively ordering, CEO Vas Narasimhan said during a conference call in January.
With the earlier-line nod, Novartis wants to ensure that the sites that are already using Pluvicto fully maximize their capacity and to “also accelerate our efforts to get even more sites ready in the community,” Narasimhan said.
Beyond mCRPC, Novartis expects readout this year from the PSMAddition trial for Pluvicto in metastatic hormone-sensitive prostate cancer. By Novartis’ estimate, PSMAddition represents a patient population that’s as large as the current PSMAfore indication.