The month ahead: August’s upcoming events

August is traditionally the month for holidays, but there are still a few FDA verdicts looming. The most notable is a decision on the DRD2 antagonist dordaviprone for a rare brain cancer, the driver behind Jazz Pharmaceuticals’ $935m swoop for Chimerix earlier this year.

Boehringer Ingelheim’s zongertinib could also get the nod in second-line HER2-mutated NSCLC, although that company is being tight lipped about the project’s exact PDUFA date. Boehringer is a few months ahead of its rival Bayer, whose similarly acting sevabertinib (BAY2927088) was accepted by the FDA in May for the same use, with priority review. A decision on that asset is therefore expected in November.

Rare approval?

Dordaviprone’s filing was based on uncontrolled trials showing a 28% overall response rate, plus median overall survival of 13.7 months, in a cohort of 50 patients. The asset could become the first drug specifically to target H3K27-mutant diffuse glioma; approval would also bring Jazz a valuable rare paediatric disease priority review voucher.

Still, there are hints that all might not be well. A confirmatory first-line trial, Action, is under way, but Jazz noted in its first-quarter earnings call in May that enrolment wasn’t going very well. Indeed, the company said that US recruitment had been paused in anticipation of FDA approval, to stop patients leaving the control arm to get dordaviprone via prescription.

A first interim analysis of Action is due by year-end 2025. Chimerix paid just $39m in cash and $39m in equity for dordaviprone’s originator, Oncoceutics, in 2021, but Jazz has a lot more riding on the project's success.

Outstanding verdicts

Investors are also still awaiting verdicts on several assets that had been expected in previous months. Johnson & Johnson and Genmab’s Darzalex could get the nod in smouldering myeloma (based on the Aquila trial) and in first-line, transplant-ineligible multiple myeloma (based on Cepheus).

Two Lilly projects are in front of the FDA: the SERD imlunestrant in second-line breast cancer, and the non-covalent BTK inhibitor Jaypirca in second-line CLL. The latter already has accelerated approval for third-line CLL, so the latest decision could confirm and expand its use – although there are some doubts after the Bruin CLL-321 trial met its primary endpoint of progression-free survival, but failed to show an overall survival benefit versus standard of care.

Finally, Regeneron’s CD20-targeting T-cell engager odronextamab had been due a decision by 30 July in relapsed follicular lymphoma. That company had previously also hoped for a nod in DLBCL, but didn’t refile for this use following a complete response letter last year.

August’s upcoming events

Source: OncologyPipeline.