Back in 2015, GlaxoSmithKline traded away its marketed cancer assets and began building its oncology pipeline “pretty aggressively,” as Axel Hoos, the company’s SVP of Oncology R&D, puts it. And those efforts have finally paid off.
The FDA late Wednesday green-lighted Blenrep—formerly known as belantamab mafodotin—a first-in-class antibody-drug conjugate for multiple myeloma patients who have already tried three other options.
While GSK currently has a marketed cancer med in Zejula, that drug came to it in 2018’s buyout of Tesaro. Blenrep, on the other hand, is “our first homemade, new oncology product,” Hoos said.
It’s also the first med approved to target BCMA, which Hoos called “a unique and very attractive” target for treating myeloma. The reason? When targeting BCMA, “the majority of cells you will kill are myeloma cells,” Hoos said. BCMA is not expressed on other healthy tissues throughout the body, making the approach “relatively specific” compared with others used in myeloma.
That’s not to say there aren’t others in development—but unlike those bispecific antibodies and CAR-T therapies, Blenrep is “easy to manufacture and easy to make accessible for patients,” Hoos said.
“If you look at other BCMA-targeting modalities like CAR-T cells, they’re a lot harder to use and harder to manufacture, and then they’re harder to give to a large number of patients because of qualifying or disqualifying clinical features or toxicities,” he added.
That’s not to say Blenrep is without toxicities of its own. Nearly three-quarters of patients in GSK’s phase 2 trial suffered changes to the cornea, or keratopathy—a condition that can result in dry eyes, blurry vision, and even severe vision loss. And FDA staffers were quick to flag the side effects ahead of an advisory committee meeting.
Still, the agency’s advisors voted unanimously in Blenrep’s favor, pointing to data showing the drug could shrink tumors in about one-third of patients and help them live a median 15 months.
GSK, for its part, believes it’s “in a good place to manage” the eye events, and the company put pre-treatment eye exams into its risk management plan for the newcomer.
What’s most concerning about the eye-related side effects “is that they’re new,” Hoos said. “Many people are not familiar with eye toxicity in cancer trials … they’re familiar with a lot of toxicity in cancer trials, but not this one.”
So Glaxo is taking it upon itself to spread the word. “We need to help them understand it,” Hoos said, noting that doctors “need to know how to manage the safety events, if they occur.”
In the meantime, the company will also be working to broaden Blenrep’s treatable patient population by moving the drug into earlier lines of therapy. About 10,000 patients globally receive fourth-line treatment, compared with 65,000 in the first-line setting, Hoos said in a previous interview.
“We’re pretty confident that this compound can be developed for all earlier lines … in combination with other compounds,” he said this week.