After two delays spanning more than a year, Novartis is finally gearing up for a high-stakes FDA application to expand the radiotherapy Pluvicto into earlier treatment of prostate cancer.
Novartis made the decision after patient survival data turned in Pluvicto’s favor at another preplanned analysis of the phase 3 PSMAfore trial. The study is pitting the drug against a change of androgen receptor inhibitor in patients with PSMA-positive, metastatic castration-resistant prostate cancer who hadn’t received chemotherapy.
The updated result now includes 75% of deaths before the final analysis of overall survival. Previously, when the trial had accrued 45% of death events, a preliminary trend linked Pluvicto to a 16% increased risk of death before adjusting for patient crossovers.
Leaping into the pre-chemo setting is key in Novartis’ $3 billion-plus peak sales estimate for Pluvicto, which is currently approved for patients after failure on chemotherapy.
In a Thursday press release, Novartis said it plans to file Pluvicto for a pre-chemo approval in the second half of 2024. That leaves another three months at a minimum if the company should file first thing in July. The gap is a bit long considering that the application has already been delayed twice because of immature data. Novartis has been preparing for this day all this time, having expressed much confidence in the 75% data cut.
Although the level of death risks has now flipped between the two trial arms in PSMAfore, question remains as to whether the current positive overall survival trend, at 75% maturity, is strong enough to convince the FDA that it’s sustainable or if it’s just a transient spark.
In response to a Fierce Pharma inquiry about whether even longer-term results will be included in the expected filing, a Novartis spokesperson pointed to the company’s press release, which states that it plans to file based on the latest readout.
The PSMAfore trial first met its primary endpoint in December 2022, as Pluvicto demonstrated a benefit in prolonging the time before tumor progression or death. But the FDA at that time asked to see more mature overall survival analysis, pushing back Novartis’ planned filing date to the second half of 2023.
Data unveiled in October 2023 showed that Pluvicto cut the risk of disease worsening or death by 57% compared with a change of androgen receptor inhibitor. But the negative trend in overall survival at that time again prevented a potential FDA submission.
Novartis has attributed the lackluster overall survival showing in PSMAfore to a high rate of control arm patients who later received Pluvicto following disease progression. At the previous data cut, 84% of control patients had got Pluvicto. After adjusting for crossover, investigators at that time found Pluvicto could reduce the risk of death by 20%.
The FDA has recently repeatedly stressed the importance of any cancer drug application at least not having a negative trend in overall survival to suggest any potential detriment to patients’ life expectancy.
In a very similar case to Pluvicto’s, a phase 3 trial of Bristol Myers Squibb’s CAR-T therapy Abecma was also troubled by high patient crossover in an earlier multiple myeloma treatment setting. An external advisory committee to the FDA recently backed the drug based on a strong progression-free survival benefit and no apparent detriment to patient survival over a relatively longer term.