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.
Those efforts have finally paid off with a new approval. But just how much remains to be seen, with analysts expecting "limited adoption" for the company's newcomer thanks to a black box warning for eye toxicity.
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 four other options, including an anti-CD38 monoclonal antibody, a proteasome inhibitor and an immunomodulatory agent.
Blenrep will bear a list price of $8,277 per vial, which comes out to an estimated monthly cost of $23,900 based on average patient weight, a GSK spokesperson said by email. "We are committed to helping patients access our medications and offer a variety of access and reimbursement services for all GSK oncology products," she added.
While GSK currently has a marketed cancer med in Zejula, that drug arrived with the company's 2018 Tesaro buyout. 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 healthy tissues throughout the body, making the approach “relatively specific” compared with others used in myeloma.
"This is a significant milestone, and an accomplishment for the drug’s developers," SVB Leerink analyst Geoffrey Porges wrote in a Thursday note to clients.
While there are plenty of other BCMA-targeting therapies in development, 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. But Porges expects the drug's "significant baggage" to result in "disappointing adoption and relatively modest sales."
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 therapy.
What’s most worrisome 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.
But Porges isn't sure it'll get much play. Myeloma patients "now have a variety of treatment options from several generations of different (proteasome inhibitors and immunomodulatory agents) to choose from," he wrote, and "the growing adoption of anti-CD38 antibodies" Darzalex from Johnson & Johnson and Sarclisa from Sanofi "also expanded physicians’ toolbox."
"We expect most usage of Blenrep will be in fourth line and beyond, with limited share in earlier lines," he concluded, forecasting £287 million ($377 million) in global sales in 2021 and £1.47 billion ($1.93 billion) in 2024.