GSK's CAR-T rival Blenrep fails multiple myeloma trial, endangering its accelerated approval

GSK’s dream just turned into a nightmare.

The company’s BCMA-targeted Blenrep has failed a phase 3 trial in relapsed or refractory multiple myeloma. The GSK antibody-drug conjugate didn’t outdo Bristol Myers Squibb’s Pomalyst and low-dose dexamethasone at slowing disease progression or death, the company said Monday.

The DREAMM-3 trial flop is a blow to GSK’s oncology ambitions; the British pharma has projected Blenrep could reach more than 3 billion pounds sterling in peak sales. And it puts Blenrep’s accelerated approval in multiple myeloma in danger.

Blenrep won an FDA accelerated approval in 2020 for treating myeloma patients after four prior therapies based on tumor shrinkage data from a single-arm study. A randomized study comparing Blenrep with standard of care and using progression-free survival as the primary endpoint is required to confirm the drug’s efficacy.

DREAMM-3 pitted Blenrep monotherapy against the Pomalyst-dexamethasone regimen in patients who had received at least two prior lines of therapy. The study found Blenrep had no notable effects on progression-free survival, even though patients who got the GSK drug lived longer without disease progression at the median, going 11.2 months versus seven months. The discrepancy suggests a possible worsening of effect in the Blenrep arm after the median point.

Blenrep also didn’t do much better at shrinking tumors, with a response rate of 41% compared with 36% for the control group. It so far also showed no benefit at preventing deaths. At the time of the analysis, when 37.5% of the trial patients had died, Blenrep and control arms recorded median survival of 21.2 months and 21.1 months, respectively. Patients on the GSK drug had a 14% higher risk of death.

Seeking a silver lining, GSK pointed to a finding that Blenrep had a deeper response, with 25% of patients experiencing a very good partial response or better, compared with 8% for the Pomalyst combo arm. And Blenrep’s duration of response appears better: 76.8% of Blenrep patients were still responding at 12 months, versus 48.4% for the control group. But with the failure on the primary endpoint, those additional data likely don’t matter.

GSK is in the process of sharing the DREAMM-3 data with regulators, and “discussions with health authorities are currently ongoing,” the company said.

Two more phase 3 trials of Blenrep are expected to read out soon in the first half of 2023. The DREAMM-7 study pits Blenrep against Johnson & Johnson’s CD38 antibody Darzalex in their respective combinations with Takeda’s Velcade and dexamethasone in multiple myeloma patients who have previously been treated with at least one prior line of therapy.

The DREAMM-8 trial is also studying Blenrep in the second-line setting, but it’s testing the drug head-to-head against Velcade in their respective combinations with Pomalyst and dexamethasone.

Despite the trial flop, there may be hope for the GSK drug. The FDA has previously allowed cancer accelerated approvals to remain on the market despite a confirmatory fail, especially when another study that could serve as the new confirmatory trial nears a readout. Given the imminent readout from the other two DREAMM studies, the FDA likely won’t act on Blenrep now.

But the FDA’s decision to keep an accelerated approval intact also depends on whether unmet medical need still exists in the drug’s approved use. There, Blenrep’s argument is relatively weak.

After Blenrep’s approval in 2020, the FDA has since cleared two BCMA-targeted CAR-T therapies: Bristol Myers and 2seventy bio’s Abecma in 2021 and J&J and Legend Biotech’s Carvykti in 2022. What’s more, the agency a few days ago just greenlighted J&J’s BCMA bispecific Tecvayli. All of those approvals came in late-line multiple myeloma.

Although all those BCMA nods are currently accelerated approvals based on single-arm tumor response data, BMS in August said Abecma beat standard combo treatments on progression-free survival in the randomized KarMMa-3 study. That phase 3 win puts Abecma on track to a third-line myeloma approval and a conversion of its accelerated approval into a full nod.

Blenrep’s tumor response rate lags the other BCMA drugs out there in cross-trial comparisons, and its uptake shows. As the first BCMA agent on the market, Blenrep sold 36 million pounds ($41 million) in the third quarter, up 32% year over year at constant currencies mainly thanks to Europe. By comparison, Carvykti generated $55 million in the third quarter during its first full quarter on the market. And Abecma brought in $107 million, good for 59% year-over-year growth.