“We are pleased the committee recognized the potential for belantamab mafodotin to help patients who have relapsed or refractory multiple myeloma, an incurable disease with limited treatment options,” said Axel Hoos, senior vice president and heat of Oncology R&D for GSK.
It’s a yes for GSK’s multiple myeloma drug belantamab mafodotin.
The U.S. Food and Drug Administration (FDA)’s Oncologic Drugs Advisory Committee (ODAC) unanimously voted, 12 to 0, to recommend GlaxoSmithKline’s belantamab mafodotin as a monotherapy for relapsed or refractory multiple myeloma in patients who have had at least four previous therapies. The previous therapies include an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody. Two members of the committee could not participate in the final vote due to technical communication difficulties.
“We are pleased the committee recognized the potential for belantamab mafodotin to help patients who have relapsed or refractory multiple myeloma, an incurable disease with limited treatment options,” said Axel Hoos, senior vice president and heat of Oncology R&D for GSK. “We look forward to working with the FDA as they complete their review of our Biologics License Application.”
The Adcom was evaluating the company’s BLA based on data from the DREAMM clinical grail program, which included the pivotal DREAMM-2 trial of heavily pre-treated patients whose multiple myeloma was actively progressing despite current standard of care.
The FDA is not required to follow the recommendation of the Adcom, although they often do. The agency granted the drug breakthrough therapy designation in 2017 and gave the BLA priority review designation. It is also under accelerated assessment by the European Medicines Agency.
Belantamab mafodotin is an antibody drug conjugate made up of a humanized anti-B cell maturation antigen (BCMA) monoclonal antibody attached to the cytotoxic drug auristatin F by way of a non-cleavable linker. The linker is licensed from Seattle Genetics and the monoclonal antibody is created using POTELLIGENT Technology licensed from BioWa.
GSK is working to build out its oncology pipeline, and belantamab mafodotin is one of three the company hopes to expand with. The FDA approved the British company’s Zejula (niraparib), an oral, once-daily poly (ADP-ribose) polymerase (PARP) inhibitor by itself in April for advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy. GlaxoSmithKline is hoping to begin a trial with the drug for endometrial cancer by the end of this year.
Analysts with Jefferies believe belantamab mafodotin, if approved, could peak at $1.5 billion. “Not all patients will be willing to accept the ocular toxicity concerns, and we see potential downside risk,” they wrote in a note to clients.
The clinical trials showed belantamab mafodotin affected vision in 17% of patients, including corneal degeneration. The Adcom apparently felt that the benefits of the drug outweighed the vision loss issue. The vision issues have not been observed in other multiple myeloma drugs. The vision problems include dry eyes, blurry vision, and in some cases, severe loss of vision. In 97 patients receiving the lower dose, 44% had at least one instance of severe keratopathy, although no patients lost their vision permanently, according to the company.
The FDA, however, wrote, “FDA disagrees with the Applicant’s statement that permanent changes in vision or damage to the cornea have been avoided to date.”
In the trials, the lower dose of the drug decreased tumors in about a third of patients, adding a median of 15 months of life. That’s approximately twice as long as patients get with other drugs.
The company also indicates they are working to ensure doctors and patients can manage the side effects. This includes providing eye exams before each cycle of belantamab mafodotin and decreasing or delaying the next dose as needed. The FDA was skeptical, however, writing, “There are no therapeutic strategies identified to mitigate the ocular toxicity with belantamab mafodotin. Despite implementing dose modifications, ocular toxicities were recurrent and persistent.”
Philip Hoffman, chairperson of the committee and a professor of medicine at the University of Chicago, stated, “I voted yes for reasons we’ve pretty much heard. I think that it seems clear that this is an active agent. The toxicity is certainly not life-threatening. I do think patients are probably willing to take this risk and I think the mitigation strategy the company has outlined for [eye] exams before each dosing … is reasonable and addresses the concerns.”
