FDA red and green lights: February 2025

February might be the month of love, but the FDA only bestowed its favour on three oncology drugs last month: Pfizer/Astellas’s anti-CD30 ADC Adcetris, SpringWorks’ MEK inhibitor Gomekli, and Ono’s CSF-1R inhibitor Romvimza.

Adcetris’s green light, in third-line large B-cell lymphoma ineligible for stem cell transplant or Car-T, is its eighth approval. However, it nearly didn’t happen at all: the drug’s originator, Seagen, deprioritised the third-line Echelon-3 trial on which the latest nod was based, cutting its target enrolment and changing its primary endpoint from PFS to OS.

Despite this, the trial reported a 37% reduction in risk of death with Adcetris plus Revlimid and Rituxan, versus Revlimid and Rituxan alone. Another surprise was that the survival benefit was seen across different levels of CD30 expression, including low expressers.

One question now is how big this indication can become for Adcetris, which sold $1.1bn in 2024, almost all in the US. Competition could come from Roche’s anti-CD79b ADC Polivy, which is indicated for third-line DLBCL, in combination with bendamustine and Rituxan. Anti-CD20 T-cell engagers like AbbVie/Genmab’s Epkinly and Roche’s Columvi also have accelerated approvals for third-line use.

SpringWorks takes on Astra

Meanwhile, SpringWorks now has the tough task of going up against AstraZeneca, after bagging approval for Gomekli (mirdametinib) in adults and children with symptomatic plexiform neurofibromas caused by the genetic condition neurofibromatosis type 1.

Astra’s rival MEK inhibitor Koselugo has been approved for NF1-PN since 2020, but only in children; Gomekli also has the advantage of being available as a dispersible tablet, while Koselugo only comes in capsule form.

Despite this, Koselugo sold $631m in 2024, and could also be heading for adult use: Astra revealed last year that its phase 3 Komet study in adults met its primary endpoint, showing an ORR improvement versus placebo.

Other indications might be on the cards for Gomekli, noted Evercore ISI’s Cory Kasimov, who highlighted an ongoing investigator-sponsored phase 2 study in paediatric low-grade glioma.

Earlier in February Merck KGaA disclosed an interest in acquiring SpringWorks, which also has an approved desmoid tumour therapy, Ogsiveo, although no deal has yet emerged.

Ono challenges Daiichi

The final oncology approval of February will also set up a clash, this time between two Japanese companies. Ono got the go-ahead for its CSF-1R inhibitor Romvimza in adults with tenosynovial giant cell tumour (TGCT) unsuitable for surgical resection.

Daiichi already markets Turalio, which additionally hits KIT and FLT3, for this use. On a cross-trial basis response rates between Romvimza and Turalio look similar, but Romvimza seems more tolerable, and has managed to avoid the black box warning for liver injury and the REMS programme that hit Turalio.

But Ono, which gained Romvimza (vimseltinib) through the $2.4bn purchase of Deciphera, could soon be facing another challenger: Merck KGaA/Abbisko’s pimicotinib recently produced impressive efficacy in its phase 3 Manuever trial. No details of filing plans have yet emerged, however, and there are also doubts about whether TGCT, which affects around 9,000 US patients, could support two players, let alone three.

Selected February 2025 US regulatory decisions in oncology

Source: OncologyPipeline.