FDA red and green lights: April 2025

Of five US oncology approvals in April, four were for checkpoint inhibitors. Bristol Myers Squibb’s Opdivo added two new strings to its bow, while it was better late than never for Akeso, which finally got two nods for penpulimab after a years-long Covid delay. Still, penpulimab is no longer a top priority for Akeso, which is riding high on the PD-(L)1 x VEGF bispecific wave.

Outside checkpoint blockade, there was also full approval for Bayer’s NTRK inhibitor Vitrakvi, confirming an accelerated nod in 2018 for solid tumours with NTRK gene fusion and no alternative therapies.

NTRK fusions are rare, but Bayer paid $400m up front to partner with Loxo on Vitrakvi in 2017, alongside the now-discontinued selitrectinib. In 2019 the German group acquired full rights to both compounds, following Lilly’s purchase of Loxo. The question now is whether that was money well spent; Bayer didn’t split out Vitrakvi sales in its 2024 earnings presentation.

Accelerated to full

Opdivo’s two April green lights also converted accelerated approvals to full. The first was for Opdivo plus Yervoy in front-line MSI-high/mismatch repair-deficient colorectal cancer, based on Checkmate-8HW, setting up yet another checkpoint battle between Bristol and Merck.

Opdivo, with or without Yervoy, got an accelerated nod in 2017 for second-line MSI-high/dMMR colorectal cancer. The latest approval converts the monotherapy use to a full green light, as well as expanding the combo into the front line.

The second April approval was for Opdivo plus Yervoy in first-line liver cancer, based on the CheckMate-9DW trial; that verdict had been expected based on robust data at last year’s ASCO meeting, and follows a 2020 accelerated green light for the combo in second-line liver cancer.

Roche and Astra both have anti-PD-(L)1 combos on the market for first-line liver cancer, in Tecentriq plus Avastin, and Imfinzi plus Imjudo, respectively. Opdivo monotherapy previously failed in this setting in Checkmate-459.

Checkpoint latecomer

Meanwhile, Akeso’s penpulimab became the 12th PD-(L)1 blocker, and the third China-originated checkpoint inhibitor, to gain US approval. The company filed the project with the FDA back in May 2021 for third-line nasopharyngeal carcinoma, but things later went quiet, and the filing was assumed to have been held up by Covid-related travel restrictions and possible CRLs.

Akeso told ApexOnco in 2024 that, although the filing was still “in progress”, the project was no longer a priority, given the group’s work on bispecific MAbs like the PD-1 x VEGF-targeting ivonescimab.

Last month, as well as approving third-line use, the FDA greenlit a first-line nasopharyngeal chemo combo. The question now is whether penpulimab will be launched in the US, something that will depend on Akeso finding a partner.

Selected April 2025 US regulatory decisions in oncology

Notes: AA=accelerated approval; HCC=hepatocellular carcinoma. Source: OncologyPipeline.