GSK’s antibody-drug conjugate Blenrep has mounted a sizable patient survival benefit among certain multiple myeloma patients in a head-to-head comparison against Johnson & Johnson’s industry-leading Darzalex.
The GSK drug significantly pared down the risk of death by 42% compared with Darzalex in their respective combinations with bortezomib and dexamethasone (Vd) when used as a second- or later-line treatment for myeloma. The result came from a planned interim analysis of the phase 3 DREAMM-7 trial and was presented at the American Society of Hematology annual meeting.
More than half of trial patients were still alive in both arms after a median follow-up of 39.4 months. Based on the current trends, investigators projected that the median overall survival for the Blenrep group would reach 84 months, versus 51 months for those in the Darzalex arm.
As a line chart of death events shows, Blenrep’s survival advantage over Darzalex started to appear from around four months after treatment, later widening and sustaining over time.
Doctors often use five-year survival rates to describe a patient’s prognosis and plan treatments.
“If you’re improving five-year survival rates, you’re doing something really good for patients,” Hesham Abdullah, M.D., GSK’s head of oncology R&D, said in an interview with Fierce Pharma. “I think what you see in the DREAMM-7 overall survival data is the potential for that to happen.”
For now, the estimated three-year overall survival rates were 74% and 60% for the Blenrep and Darzalex arms, respectively.
The latest overall survival win builds on DREAMM-7’s previous success on its primary endpoint, progression-free survival, in which the Blenrep-Vd regimen significantly slashed the risk of progression or death by 59% versus Darazlex-Vd.
In the new analysis, the Blenrep combo also reduced the risk of progression following a subsequent therapy or death by 41%, although the data point doesn’t carry statistical significance.
Based on DREAMM-7 and another positive phase 3 trial, DREAMM-8 for Blenrep’s combination with Bristol Myers Squibb’s Pomalyst and dexamethasone, the FDA has accepted GSK’s application for the BCMA-directed ADC as a second-line myeloma treatment. The agency is set to make a decision by July 23, 2025.
With two positive phase 3 trials under the belt, Blenrep looks likely to return to the U.S. after GSK pulled it off the market late 2022 following a phase 3 monotherapy flop.
GSK is now looking to start a phase 3 trial in the first-line setting shortly, Abdullah said. The DREAMM-10 study will once again pit Blenrep against Darzalex, this time as part of front-line combinations with Bristol Myers Squibb's Revlimid and dexamethasone (Rd). The Darzalex-Rd regimen won the FDA’s approval mid-2019 for newly diagnosed transplant-ineligible myeloma based on the phase 3 MAIA trial showing it reduced the risk of progression or death by 44% over Rd alone.
With various approved combinations, Darzalex is currently the world’s top-selling myeloma drug, generating global sales of $8.6 billion in the first nine months of 2024.
Meanwhile, quadruplets using CD38 antibodies are starting to replace triplets in certain myeloma settings. In September, the FDA cleared Sanofi’s Sarclisa to be used alongside VRd in first-line transplant-ineligible patients. And J&J’s subcutaneous Darzalex, plus VRd, got the go-ahead in transplant-eligible patients in July.
GSK has tested the Blenrep-VRd idea in a phase 1 dose optimization study coded DREAMM-9. Across eight cohorts of altogether more than 100 patients with newly diagnosed transplant-ineligible myeloma, various doses of the quadruplet triggered a complete response rate of 63%, according to an update at the ASH conference.
Ocular toxicity, including decreasing visual acuity, has been a top concern for Blenrep. In DREAMM-7, eye-related side effects led to a 10% rate of treatment discontinuations in the Blenrep arm, according to GSK. In DREAMM-9, ocular events of grade 3 or above were reported in 55% of patients, with higher rates in cohorts testing higher, more frequent doses.
The company says it has worked out a dosing practice to help doctors mitigate eye problems. As to whether doctors will find ocular toxicity easy to manage in the real world, Abdullah pointed to how immune adverse events were initially a big concern for checkpoint inhibitors until doctors got familiar with them.
Moving into the front line, GSK is using lower doses and stretched-out dosing schedules for Blenrep, Abdullah said.