Daratumumab

GSK expects Blenrep to be a "material growth driver" over the next few years, Chief Scientific Officer Tony Wood, Ph.D., said on a call with reporters. Three years after its global market withdrawal and months after a negative advisory committee vote, GSK can officially call it a comeback for its multiple myeloma drug Blenrep in the U.S., albeit with a more limited label than anticipated.The FDA decided that the antibody-drug conjugate can return to the U.S. market in a slightly different form, this time as a combination treatment with Takeda’s Velcade (bortezomib) and the corticosteroid dexamethasone (BVd) in adults with relapsed or refractory multiple myeloma who have received at least two prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent. Previously, Blenrep was sold as a monotherapy in fourth-line multiple myeloma. But, when the drug failed a confirmatory trial, GSK pulled the drug from the market two years after its initial approval in 2020.In its effort to bring Blenrep across the FDA finish line again, GSK studied the drug as a second-line therapy as part of the BVd combination and in a separate combination with Bristol Myers Squibb’s Pomalyst (pomalidomide) plus dexamethasone (BPd) in the pivotal DREAMM-7 and DREAMM-8 trials. Although both studies showed statistically significant and clinically meaningful improvements in progression-free survival for their respective regimens, the FDA’s delayed approval is only supported by DREAMM-7 results for BVd and stipulates its use in a later treatment line. The DREAMM-7 trial enrolled patients in the second line of treatment or later, while the new approval covers third-line use and later.In DREAMM-7, the Blenrep combo cut the risk of death by 51% and tripled the control arm's progression-free survival to a median of 31.3 months, compared to 10.4 months for a daratumumab-based triplet. Even in its one approved combination, the drug can still meet an “urgent need for new and novel therapies, as nearly all patients with multiple myeloma experience relapse,” Chief Scientific Officer Tony Wood, Ph.D., said in a press release. “We believe Blenrep can redefine treatment for patients with multiple myeloma in all parts of the world, and we are accelerating its development in earlier lines of therapy to support its use across all stages of this difficult-to-treat cancer,” Wood added. A rocky road to approval  Blenrep’s odds of returning to the U.S. market seemed low after a negative vote from the FDA’s Oncologic Drugs Advisory Committee in July, when committee members couldn’t say that the benefits of the drug outweighed concerns about proposed doses, potential safety issues and the demographics of GSK’s trial population.The FDA also had its qualms, pointing to "high rates of ocular toxicity" in a pre-meeting briefing document. GSK later submitted undisclosed “additional information” to support its Blenrep approval bid, which the FDA took until Oct. 23 to review in a postponed decision.GSK worked with the FDA to address the ocular toxicity concerns through a “streamlined” Risk Evaluation and Mitigation Strategy, it said in the release, proposing simplified patient forms and efficient communication between doctors and eye care specialists to support patient safety. Blenrep will be entering an evolved multiple myeloma treatment market after its prior withdrawal, as CAR-T therapies such as Johnson & Johnson and Legend Biotech’s BCMA CAR-T therapy Carvykti have been gaining momentum over the years. The main contender, however, remains J&J’s leading Darzalex.Although Blenrep beat Darzalex in a head-to-head overall survival comparison last year, GSK might have its work cut out for it in nabbing market share. After all, the established J&J blockbuster is something of an “800-pound gorilla” that looks to remain so, David Dahan, a senior analyst at Citeline, told Fierce Pharma in a recent interview.GSK, meanwhile, points out that its offering is the only anti-BCMA agent that can be administered across healthcare settings, including in community centers, where 70% of patients receive care, Wood noted in the release. The accessibility edge makes for a "very, very competitive product here that’s going to be compelling for community-based physicians—compelling for older, more frail patients,” Chief Commercial Officer Luke Miels said in 2024. GSK previously put Blenrep’s peak sales estimate at more than 3 billion pounds sterling (about $4 billion), although that assumption was based on a nod in the second-line treatment setting. Still, the company maintains that the drug will be a “material growth driver” in the next three to four years, Wood said on a Thursday call with reporters.