GSK's Blenrep's back in US, but with a narrower label

Against the odds, GSK has secured FDA approval for its multiple myeloma therapy Blenrep, three years after it was removed from sale.

Anti-BCMA antibody-drug conjugate (ADC) Blenrep (belantamab mafodotin) has made it back to the US market as a third-line treatment for multiple myeloma, in combination with Takeda's Velcade (bortezomib) and dexamethasone, despite a lengthened FDA review and a vote against its approval by the agency's Oncologic Drugs Advisory Committee (ODAC) in July.

It's not a complete win for GSK, however, as the FDA has not approved a second regimen combining the drug with Bristol Myers Squibb's Pomalyst (pomalidomide) and dexamethasone, possibly related to concerns at the ODAC about ocular toxicity with the ADC that was more pronounced with this regimen.

It has also restricted use of the drug to the third-line setting, while other markets that have approved the drug - including the EU, UK, and Japan - have given the go-ahead for second-line use. It was relaunched in June, starting its rollout in England, although notably only the regimen with Velcade and dexamethasone has been cleared for NHS use.

The narrower label is a blow to GSK's hopes of restoring the fortunes of the would-be blockbuster product, but still a step forward after Blenrep was withdrawn from the market in 2022 as a fifth-line or later therapy for multiple myeloma – two years after launch with an accelerated approval – after failing a confirmatory trial.

With GSK pushing for peak sales of around £3 billion ($4 billion) for the drug, the pace of its rollout – and the impact of its narrow label in the big US market – will come in for close scrutiny.

The resurrection of Blenrep has been driven by results from the DREAMM-7 and DREAMM-8 trials, which demonstrated its ability to improve clinical outcomes when administered alongside other therapies as a second-line option after initial treatment with lenalidomide-based therapy for the incurable bone marrow cancer.

The US label draws on the DREAMM-7 trial, which showed a 51% reduction in the risk of death and tripled median progression-free survival in a third-line or later myeloma population compared to a comparator triple therapy based on Genmab and Johnson & Johnson's anti-CD37 antibody Darzalex (daratumumab).

"As the only anti-BCMA agent that can be administered across healthcare settings, including in community centres where 70% of patients receive care, Blenrep fulfils a major patient need," commented Tony Wood, GSK's chief scientific officer.

GSK has acknowledged that achieving Blenrep sales targets will depend on expanding its use into the first-line setting, and to that end it is running the DREAMM-10 study in newly diagnosed, transplant-ineligible multiple myeloma patients, pitting Blenrep plus lenalidomide and dexamethasone against Darzalex plus lenalidomide and dexamethasone.