ESMO 2023 – Pluvicto’s big splash gets an early preview

Novartis had already disclosed that Pluvicto’s PSMAfore trial had met its primary endpoint. Today investors got a preview of the magnitude of the benefit with Pluvicto over androgen receptor-directed therapy, thanks to the leak of an ESMO late-breaking abstract. 

The data look practice-changing, according to B Riley analysts, who alerted investors to the leak. The bar is now set for the next radiopharmaceutical in line, PNT2002, developed by Point Biopharma, which is soon to become part of Lilly.

PSMAfore flagged

Pluvicto is already approved in post-chemo castration-resistant metastatic prostate cancer; with PSMAfore Novartis hopes to move it into the pre-chemo setting. 

The trial enrolled patients who had progressed on one second-generation androgen receptor pathway inhibitor, such as Zytiga or Xtandi, who were randomised to receive either Pluvicto or a different androgen-receptor-targeting therapy.

The primary endpoint was radiographic progression-free survival. Median rPFS in Pluvicto-treated patients was 12.0 months, versus 5.6 months in the control group, giving a hazard ratio of 0.43, according to the leaked abstract.

These numbers were in line with the 11-13 months and 5-6 months that Jefferies analysts predicted for Pluvicto and control respectively, ahead of both ESMO and the data leak.

Flying the flag: leaked results from PSMAfore

Note: PSMAfore enrolled patients previously treated with an androgen-receptor pathway inhibitor (ARPI), who were randomised to Pluvicto or a different ARPI. Source: B Riley Securities.

Another important factor in Pluvicto’s uptake in this new use will be tolerability. Here, the available data look promising, with a lower rate of grade 3 adverse events with Pluvicto versus control.

More details will be needed, and safety will be something to look at closely when full PSMAfore data are presented at ESMO on Monday. Doctors are particularly concerned about bone marrow toxicity.

ESMO attendees will also be interested in data on overall survival, a key secondary endpoint. Novartis said the presentation would include the second interim OS analysis. 

A filing in the new setting was held up by the FDA asking for a more mature survival analysis; Novartis is planning a submission in the fourth quarter.

Radiopharmaceutical interest grows

Novartis’s new radiopharmaceutical rival Lilly now knows what it will have to show with PNT2002. That PSMA-targeting project’s phase 3 Splash trial, also in pre-chemo castration-resistant metastatic prostate cancer, is due to yield data in the fourth quarter of this year.

Lilly took a gamble by making a move for Point before the Splash readout, but even if the data fall short it might not be a disaster. At the time of the deal Lilly made much of Point’s radiopharmaceutical manufacturing capabilities, suggesting that this was a significant factor. The importance of manufacturing should not be underestimated, with Novartis previously running into supply problems with Pluvicto and Lutathera.

Jefferies analysts also speculated that the deal might have mainly been driven by Point’s early-stage pipeline, in particular the preclinical next-generation PSMA-targeted project, PNT2001. This uses the alpha-emitting radioisotope actinium-225, said to be more potent than the beta-emitting lutetium-177 employed in PNT2002 and Pluvicto.

And Point’s price tag is small change for Lilly, the largest pharma company by market cap.

A bigger question might be why Point sold itself relatively cheaply before its big readout, as a positive result would presumably have helped it command a higher price. In the next few months it should become apparent if Point blinked too soon.

After this story was published ESMO took the decision to reveal all late-breaking abstracts immediately.