FDA red and green lights: August 2025

August saw just two US oncology approvals, of Jazz’s Chimerix-originated Modeyso, and Boehringer Ingelheim’s zongertinib, now branded Hernexeos.

Both gained an accelerated nod: Modeyso for an ultra-rare brain tumour, H3 K27M-mutated diffuse midline glioma, and Hernexeos for relapsed HER2-mutant non-small lung cancer.

Boehringer first

Boehringer has therefore beaten its rival Bayer to the punch; the latter is also developing a targeted small molecule, sevabertinib (BAY2927088). However, Bayer isn’t too far behind: sevabertinib was accepted by the FDA for second-line HER2m NSCLC with priority review in May, making an approval decision likely in November.

Hernexeos might have a slight edge on efficacy: the drug’s label cites an ORR of 75% in the uncontrolled Beamion Lung-1 trial, while at last year’s World Lung meeting sevabertinib produced an ORR of 72% in cohort D of the Soho-1 study – however, this dwindled to 61% in a larger dataset presented at this year’s ASCO.

Liver toxicity looked more pronounced with Hernexeos; indeed, Boehringer only filed the lower dose tested, 120mg, saying this produced the optimal benefit/risk ratio. The drug’s label includes a warning on hepatotoxicity, but the company will be relieved that the FDA didn’t slap on a more serious black box warning.

Hernexeos’s label also highlights left ventricular dysfunction and interstitial lung disease as potential issues.

Meanwhile, sevabertinib showed a relatively high rate of dose reductions and discontinuations, plus one death, in Soho-1. Diarrhoea seems to be a particularly problematic side effect, although Bayer claimed no cases of ILD or pneumonitis in the trial.

Around 2-4% of NSCLC patients are thought to harbour HER2-activation mutations. Both assets are in confirmatory trials in first-line HER2m NSCLC: Beamion Lung-2 for Hernexeos, and Soho-2 for sevabertinib, with data from both expected next year. Boehringer also has hopes in patients with wild-type, but overexpressed or amplified HER2.

Modeyso nod

Jazz, meanwhile, is also looking at a niche with Modeyso: H3 K27M-mutated diffuse midline glioma affects around 2,000 patients per year in the US, according to the company.

Jazz paid $935m to get its hands on the DRD2 antagonist, via its March acquisition of Chimerix, so must believe that sales will justify this outlay.

Modeyso’s approval was based on an overall response rate of 22% among 50 patients who met prespecified criteria in a pooled analysis of five uncontrolled trials. Jazz will need to confirm the drug’s benefit in the confirmatory first-line Action trial, which is due its first interim analysis by year-end 2025.

Selected August 2025 US regulatory decisions in oncology

Source: OncologyPipeline.