In surprise move, GSK pulls Blenrep's accelerated approval only days after confirmatory trial flop

GSK is setting a new standard for speed when it comes to withdrawing an accelerated approval after a confirmatory trial failure.

The British big pharma is pulling Blenrep from the U.S. market at the request of the FDA, the company said Tuesday. The move comes just 15 days after GSK’s announcement that Blenrep failed to top a pairing of Bristol Myers Squibb’s Pomalyst and dexamethasone in relapsed or refractory multiple myeloma after at least two prior lines of therapy.

Blenrep, an antibody-drug conjugate, became the first BCMA-targeted therapy to win an FDA approval back in 2020. At that time, tumor shrinkage data led to an accelerated approval in fifth-line multiple myeloma. Since then, the FDA has approved several BCMA-targeted therapies for late-line myeloma, including CAR-T therapies from Bristol Myers Squibb and a partnership between Johnson & Johnson and Legend Biotech, plus an off-the-shelf bispecific

GSK’s decision to pull Blenrep this fast comes as a surprise because the company has two other phase 3 trials with imminent readouts expected in the first half of 2023. In the past, the FDA has allowed questionable accelerated approvals to remain in place, even after phase 3 flops, when another trial could serve as the new confirmatory study.

Even though Blenrep failed as a monotherapy in the DREAMM-3 trial, triggering the current withdrawal, the two ongoing late-stage studies, DREAMM-7 and DREAMM-8, are testing Blenrep in combinations in an earlier treatment setting for patients who have tried at least one prior line of therapy. But because of the market withdrawal, GSK would have to go through a new biologics license application for Blenrep if those studies are successful, rather than a potentially shorter supplemental application.

Despite the setback, GSK is still standing by its ambition to reach £33 billion in sales by 2031 without contributions from any acquisitions, a company spokesperson told Fierce Pharma. GSK shared the goal last June when it committed to spinning off its consumer group, which eventually became Haleon. At that time, GSK projected that Blenrep could reach over £3 billion in annual sales.

GSK remains confident in Blenrep and its “potential to deliver meaningful results” from the combo trials, the spokesperson said. The company has already reported positive readouts from several trials testing Blenrep in combinations with standard-of-care therapies in earlier lines of treatment, the spokesperson added.

Blenrep’s withdrawal marks the second setback to GSK’s oncology ambitions in recent weeks. Earlier this month, the drugmaker was forced to limit Zejula’s indication in second-line maintenance treatment of ovarian cancer.

Meanwhile, the FDA could be setting an example with GSK about how it wants withdrawals of cancer accelerated approvals to proceed going forward, especially when there’s no unmet medical need.

During a discussion last week with FDA Commissioner Robert Califf, M.D., FDA’s oncology chief Richard Pazdur, M.D., highlighted “taking drugs off the market” after confirmatory trial failures as a major issue on his mind.

“If .. the confirmatory study has clearly failed, then I think the companies have to step up and take these drugs off the market as rapidly as possible,” Pazdur said in his conversation with Califf at the Friends of Cancer Research annual meeting.

 

RELATED: FDA wants confirmatory trials to be underway before granting accelerated cancer nods, Pazdur says

 

The longtime FDA oncology head recalled how hard the agency fought to get Avastin’s breast cancer indication withdrawn more than ten years ago following a confirmatory trial failure, calling the experience “a nightmare.”

Pazdur also mentioned various suggestions being floated in Congress to facilitate rapid removal of drugs, including having the FDA announce the removal and dealing with company disputes through standard regulatory procedures.