The approval covers Blenrep as a monotherapy — that is, without other treatments — in adults who have been treated with at least four prior therapies, have demonstrated disease progression on the last therapy, and whose disease is refractory to at least one proteasome inhibitor, one immunomodulatory treatment, and an anti-CD38 monoclonal antibody. Refractory disease is one that does not respond to treatment.
“The approval of Blenrep marks an important step forward for patients in Europe where nearly 50,000 new cases of multiple myeloma are diagnosed each year,” Hal Barron, MD, chief scientific officer and president of research and development at GSK, said in a press release.
“The EC approval of Blenrep is good news for patients with refractory multiple myeloma whose cancer continues to progress and are in dire need of new treatment options,” added Brian G.M. Durie, MD, chairman of the board of the International Myeloma Foundation. “We appreciate GSK’s efforts to bring this new therapy to patients in the EU and for the commitment to addressing the needs of the multiple myeloma community.”
Blenrep is an antibody-drug conjugate. Specifically, it consists of an antibody that targets the protein BCMA (B-cell maturation antigen), which is found on the surface of myeloma cells. Notably, Blenrep is the first BCMA-targeting therapy to be approved by the EC.
The anti-BCMA antibody is linked to auristatin F, a molecule that is toxic to cells. The basic idea behind the therapy is that the antibody, by targeting BCMA, will specifically deliver the toxin to cancer cells, killing them.
The technology used to link the antibody to the drug was developed by Seattle Genetics, which received a milestone payment from GSK following the EC approval, per a previous agreement between the two companies.
The EC approval, which follows a positive opinion from the European Medicine Agency’s Committee for Medicinal Products for Human Use, was based on data from the open-label clinical trial DREAMM-2 (NCT03525678). The GSK-funded trial enrolled 196 participants, who were treated with Blenrep at one of two doses (2.5 or 3.4 mg/kg) every three weeks.
Nearly a third (32%) of the 97 participants treated with the now-approved dose of 2.5 mg/kg had a response to treatment, with 19% showing a response that was deemed “very good” or better, as assessed by an independent review committee. Three participants had a complete response, which means the cancerous tumor was gone and there was no evidence of disease.
The median duration of the response was 11 months, and median overall survival was 13.7 months.
The most commonly reported adverse events in the 2.5 mg/kg arm of the trial were eye problems (71%). Participants also experienced abnormally low platelet levels (38%), anemia (27%), blurred vision (25%), nausea (25%), fever (23%), increased levels of the liver health marker aspartate aminotransferase (21%), infusion-related reactions (21%), and low numbers of lymphocytes (20%) — a type of immune cell.
The higher dosage had similar efficacy, but a worse safety profile, so GSK only sought approval for the lower dose.
Routine eye exams and blood analyses are recommended for people treated with Blenrep.
“Despite advances in treatment, multiple myeloma remains incurable and patients continue to cycle through therapies, with their prognosis worsening with each relapse,” said Katja Weisel, MD, of the University Medical Centre Hamburg-Eppendorf, a DREAMM-2 investigator.
“The approval of Blenrep, with its novel mechanism of action, represents a new class of treatment that patients can turn to when their cancer stops responding to other standard of care options,” Weisel said.
“I am pleased that today’s news will give patients with limited treatment options access to the first approved anti-BCMA therapy,” Barron added.
GSK is currently sponsoring additional clinical trials, including DREAMM-6 (NCT03544281) and a DREAMM-5 platform trial (NCT04126200), to evaluate Blenrep in combination with other medications to treat myeloma.