GSK has more trial evidence to support a potential comeback for its withdrawn antibody-drug conjugate Blenrep.
In patients with previously treated multiple myeloma, Blenrep beat Takeda’s Velcade in their respective combinations with Bristol Myers Squibb’s Pomalyst and the corticosteroid dexamethasone, GSK said Thursday.
The readout came earlier than expected during an interim analysis of the phase 3 DREAMM-8 trial. The trial met its primary endpoint as the Blenrep combo significantly extended the time to disease progression or death compared with the Velcade-based regimen. Patients in the study had previously received at least one prior line of therapy.
DREAMM-8 is the second phase 3 trial that GSK has been running to potentially mount a case to bring Blenrep back to the market. In late 2022, the company pulled the BCMA-targeted ADC off the U.S. market as a late-line therapy.
About three months ago, the DREAMM-7 trial also met its primary endpoint of progression-free survival early, showing that Blenrep topped Johnson & Johnson’s Darzalex in their respective combinations with Velcade and dexamethasone.
A GSK spokesperson declined to comment on the company’s regulatory strategy, only saying the drugmaker will share the results with regulators.
It’s unclear if GSK will be able to file with the FDA at the moment. In recent years, the agency has held up several drug submissions by requiring longer follow-ups to confirm no sign of detriment to patients’ life expectancy.
For now, both DREAMM-7 and DREAMM-8 have shown a positive overall survival trend, but the data were immature in both cases.
Results from both trials showed “strong clinical evidence of the robust efficacy” for Blenrep, Hesham Abdullah, GSK’s head of oncology R&D, said in a statement. “If approved, we believe these combinations have the potential to redefine the treatment of relapsed or refractory multiple myeloma and advance the standard of care.”
Still, it wouldn’t be surprising if the FDA proceeds carefully with the drug given that it has previously failed in a phase 3 trial, albeit as a monotherapy. Back in 2022, Blenrep alone couldn’t outdo the Pomalyst-dexamethasone combo when used as a third-line therapy.
The DREAMM-3 flop led GSK to quickly withdraw Blenrep’s accelerated approval in the fifth line, but the company kept the two combo studies running in hopes of one day re-entering the multiple myeloma market.
Data from the recent DREAMM-7 readout showed that Blenrep cut the risk of progression or death by 59% compared with Darzalex in their Velcade-steroid combos.
If the DREAMM-8 results are in line with DREAMM-7, Blenrep could become a $1.6 billion product at peak, analysts at J.P. Morgan wrote in a note Thursday. The team expects GSK to file for re-approval in the second half of this year, which was originally the time frame that GSK was expecting a readout from DREAMM-8.
Analysts at Citi on Thursday assigned the drug risk-adjusted sales of £2.5 billion ($3.19 billion) in 2035. It’s not the £3 billion ($3.83 billion) peak sales estimate that GSK had once targeted, but it’s much better than nothing. For now, GSK’s recently revised outlook of more than £38 billion in risk-adjusted sales by 2031 doesn’t include any contribution from Blenrep.
Still, the J.P. Morgan team noted that Blenrep’s users would be patients who’re unable to receive CAR-T or transplant, and that the drug’s ocular toxicity is a problem.
Elsewhere in the multiple myeloma field, applications for two marketed BCMA CAR-Ts in earlier lines of treatment will be discussed during an FDA advisory committee meeting next week, with overall survival expected to be the focus of the discussion.