GlaxoSmithKline blood cancer drug returns to U.S. market, but new FDA approvals remain limited
GlaxoSmithKline (GSK) has finally received long-awaited FDA approval for its blood cancer drug Blenrep. Three years after the pharmaceutical giant pulled the drug from the market, the FDA has re-approved the drug. But the new regulatory approval for Blenrep announced Thursday is more limited in approach than GSK wanted, and the drug is rejoining a market that has grown and changed since its departure.
Multiple myeloma is a blood cancer that develops in plasma cells, a type of white blood cell. Blenrep is an antibody-drug conjugate (ADC) designed to target BCMA, a protein abundant on the surface of these cancer cells. The FDA granted accelerated approval to Blenrep in 2020 as a fifth-line monotherapy for multiple myeloma. Two years later, Blenrep failed Phase 3 validation testing. GlaxoSmithKline withdrew the product from all global markets but continued clinical testing of the drug.
Blenrep's new submission to the FDA is based on two new pivotal studies, one in combination with Takeda Pharmaceutical's multiple myeloma drug Velcade and another with Bristol Myers Squibb's multiple myeloma drug Pomalyst. Both treatment options use dexamethasone, a corticosteroid. These phase 3 studies, which evaluated the drug combination as second-line or subsequent treatment, achieved statistically significant and clinically meaningful results in terms of progression-free survival measures.
Blenrep's new FDA approval only covers the drug's use in combination with Takeda's drug and as a third-line or subsequent treatment. That's more limited than a new EU approval announced in July that allowed Blenrep to be used in combination with Takeda and BMS drugs as a second-line or follow-up treatment. The FDA said its decision was based on data from 217 patients who received the Blenrep drug combination as third-line treatment. In this population, the median progression-free survival was 31.3 months in the Blenrep group and 10.4 months in the control group. Median overall survival was not reached in the study drug group compared with 35.7 months in the control group. In this pivotal study, 92% of patients reported ocular toxicity, including cases of grade 3 or 4 severity; 83% required dose adjustments to manage this complication.
Ocular toxicity is a widely known side effect of ADCs. The boxed warning on Blenrep's original label highlights blurred vision and vision loss. In May, ocular safety risks led FDA advisory committee members to vote against the drug's benefit/risk profile as part of a combination of second-line multiple myeloma treatments. Another factor that may have contributed to the no vote was the lower proportion of U.S. patients in the study.
The FDA's approval of Blenrep requires a Risk Evaluation and Mitigation Strategy (REMS), a program to monitor and manage the risk of ocular complications. In a conference call with reporters Thursday night, GSK chief scientific officer Tony Wood said Blenrep's new REMS includes optometrists and ophthalmologists. This REMS is simpler than the previous one and will also be digital, allowing clinicians to enter data on mobile devices to reduce administrative burden.
Multiple myeloma is the third most common blood cancer, after lymphoma and leukemia. Wood said the multiple myeloma treatment market is expected to reach $45 billion by 2032. Recurrence is common in this type of cancer, but retreatment with the same drug regimen often doesn't work well, meaning patients need different options.
While Blrenrep's initial approval makes it the first BCMA-targeted therapy for multiple myeloma, the market share has grown. BMS's BCMA-targeted CAR T-cell therapy Abecma is approved as a fifth-line treatment, as is partner Johnson & Johnson and Legend Biotech's Carvykti. Carvykti has since been upgraded to second-line treatment, while Abecma may now be used in third-line treatment. Tecvayli, a bispecific antibody developed by Johnson & Johnson, was approved by the FDA in 2023, bringing a new BCMA-targeted therapy to patients in need of fifth-line treatment.
BMS and Johnson & Johnson's BCMA-targeted cell therapy requires patients to be hospitalized before and after treatment. Blenrep is a 30-minute infusion every three weeks and can be given in a community hospital. That's important, Wood said, because more than 70 percent of U.S. patients are treated in community settings.
Ahead of the FDA's regulatory decision, GlaxoSmithKline said Blenrep's return to the market could generate peak sales of 3 billion pounds ($3.8 billion). These projections are based on U.S. approval of the drug for second-line use. Wood said clinical testing is ongoing to support expanded use of Blenrep, including as an earlier treatment option. He said the studies appropriately represented U.S. patients.
“Our clinical development and evidence generation programs, working closely with the FDA, continue to explore the use of Blenrep in early and all stages of multiple myeloma globally, with additional data expected in 2028,” Wood said.
Photo by GlaxoSmithKline
