Pluvicto gets a no in Europe

US and European regulators have long differed in their evaluation criteria for drug filings, a contrast highlighted again by the most recent decisions from the EU's CHMP, which appeared to take a tougher stance than the FDA did previously.

This time, those stricter decisions hit Novartis’s Pluvicto and Bristol Myers Squibb’s Opdualag. On Friday, Novartis revealed that it had withdrawn its type II variation application for Pluvicto to treat adult patients with PSMA-positive metastatic castration-resistant prostate cancer after an androgen receptor pathway inhibitor (ARPI) but prior to chemotherapy, based on data from the PSMAfore trial.

Control arm

The withdrawal was prompted by the CHMP’s concerns that the trial’s control arm, a different androgen-receptor-targeting therapy, was not appropriate. The study had already faced questions around this, as well as overall survival data, which were confounded by a high number of patients crossing over from the control group to Pluvicto. 

In contrast, the FDA approved Pluvicto for the same use last March, although Novartis's filing was delayed by a wait for updated survival results. 

PD-L1 expressers

For Bristol, the story played out a bit differently. Opdualag, a fixed dose combination of Opdivo and the Lag3 inhibitor relatlimab, is approved for first-line melanoma in both the US and Europe, but the indications differ. While the US approval covers both PD-L1-positive and negative patients, in Europe, the drug is approved only for PD-L1-negatives.

In November, Bristol submitted a type II variation to expand the approved population to include PD-L1 expressers. However, the European committee did not recommend use for these patients, though it agreed to include the data in the label.

During the presentation of the Relativity-047 trial results back in 2022, it was noted that, among PD-L1 expressers, patients had roughly the same risk of disease progression or death whether treated with Opdualag or Opdivo. The company pointed out at the time that analyses of these small subgroups were not conclusive due to insufficient statistical power.