Conditional approvals, accelerated assessments and new Phase 3 (DREAMM-3, -7 and -8) data
Blenrep previously received a conditional marketing authorisation (CMA) in the EU, with pivotal data derived from one (DREAMM-2) Phase 2, open label, randomised, two-arm study.1 The primary efficacy endpoint was overall response rate (ORR). The confirmatory Phase 3 DREAMM-32 trial failed to meet its primary endpoint (progression-free survival [PFS]), resulting in the European Medicines Agency (EMA) withdrawing the CMA.3
GlaxoSmithKline (GSK) recently published press releases detailing positive interim results from the DREAMM-74 and DREAMM-85 trials for patients with relapsed or refractory multiple myeloma (MM). These positive results could mark Blenrep's potential return as a promising treatment for relapsed refractory MM.
Overview of Blenrep's clinical trials mentioned in this summary6
| Trial name | Method | Primary Endpoint | Indication |
|---|---|---|---|
| DREAMM-2 | Phase 2 open-label, parallel-assignment trial. Patients received either belantamab mafodotin-blmf, 2.5 mg/kg or 3.4 mg/kg intravenously. | ORR | Relapsed /refractory multiple myeloma (fourth line) |
| DREAMM-3 | Phase 3 open-label, randomised , superiority trial of Blenrep (belantamab mafodotin) monotherapy versus pomalidomide in combination with low dose dexamethasone (PomDex). | PFS | Relapsed/refractory multiple myeloma |
| DREAMM-7 | Phase 3 open-label, rendomised trial evaluating Blenrep (belantamab mafodotin) combined with bortezomib plus dexamethasone (BorDex) versus daratumumab plus BorDex. | PFS | Relapsed refractory multiple myeloma (second line) |
| DREAMM-8 | Phase 3 open-label, randomised trial evaluating Blenrep (belantamab mafodotin), in combination with pomalidomide plus dexamethasone (PomDex), versus a standard of care, bortezomib plus PomDex. | PFS | Relapsed refractory multiple myeloma (second line) |
History of Blenrep's approvals
EMA
In 2020 the EMA granted Blenrep a CMA for the treatment of relapsed/refractory MM in patients who had received at least four prior treatments (fifth line) and were refractory to at least one proteasome inhibitor, one immunomodulatory agent, and an anti-CD38 monoclonal antibody. CMA was based on analyses and positive ORR data that emerged from the DREAMM-2 trial, with the final DREAMM-2 analyses and the additional Phase 3 DREAMM-3 trial serving as GSK’s obligation to confirm the efficacy, safety and benefit-risk of Blenrep.7
The EMA did not grant a full marketing authorisation because the DREAMM-2 trial did not include a comparator arm and because of the limited amount of data available at the time of approval; therefore, Blenrep’s effect on PFS and overall survival (OS) could not be confirmed.7
The EMA considered the final efficacy results from the DREAMM-2 trial to be clinically meaningful.7 The ORR in the DREAMM-2 trial was 31% (97.5% CI: 21%, 43%) and 73% of responders had response durations ≥6 months.8 However, the EMA could not confirm the efficacy of Blenrep because the DREAMM-3 trial did not meet its primary endpoint (PFS) or its secondary endpoint (OS).7
FDA
In 2020 the FDA also granted GSK’s Blenrep accelerated approval as a fifth-line therapy for adults with relapsed/refractory MM.8 The accelerated approval was based on data from the DREAMM-2 trial.
However, the accelerated approval came with a box warning as the safety data from Blenrep’s DREAMM-2 trials resulted in changes to the corneal epithelium. This resulted in severe vision loss and corneal ulcers in patients.8
Promising interim results from the DREAMM-7 and DREAMM-8 trials
In February this year, GSK published a press release about the positive interim data from the DREAMM-7 trial. It reported a statistically significant and clinically meaningful improvement in PFS from Blenrep in combination with BorDex (low dose dexamethasone) (n=243) when compared with daratumumab in combination with BorDex (n=251).4 These results were based on an independent data monitoring committee’s recommendation to unblind the trial early and analyse interim data.
GSK’s DREAMM-7 press release reported that:4
In March of this year, GSK published a second press release explaining that the DREAMM-8 trial met its primary endpoint of PFS.The DREAMM-8 trial compares Blenrep (belantamab mafodotin), in combination with pomalidomide plus dexamethasone (PomDex), versus a standard of care, bortezomib plus PomDex. These results—like those shared from the DREAMM-7 trial—were based on an independent data monitoring committee’s recommendation to unblind the trial early and analyse interim data.
GSK’s DREAMM-8 press release further reported that:5
*DREAMM-8 continues to follow up with participants for OS.
Summary
GSK’s Blenrep has been on an interesting journey. Promising ORR data emerging from the DREAMM-2 trial resulted in the FDA granting an accelerated BLA approval in 2020, and the EMA following suit with a conditional marketing authorisation. However, the confirmatory DREAMM-3 trial failed to meet its primary endpoint of PFS and Blenrep was shown to cause severe ocular side effects. The latest press releases in 2024 reported significant improvements in PFS in the DREAMM-7 and DREAMM-8 trials for Blenrep in combination with standard-of-care regimens, which could mark a turning point for Blenrep, once again as a promising treatment for patients with relapsed/refractory multiple myeloma.
