GSK’s 3 billion pounds sterling peak sales goal for its multiple myeloma drug Blenrep appears increasingly attainable thanks to a key patient survival win.

The antibody-drug conjugate (ADC) has mounted a statistically significant and clinically meaningful improvement over Johnson & Johnson’s Darzalex in extending the lives of patients with previously treated myeloma, according to an update of the phase 3 DREAMM-7 trial GSK provided Thursday.

The two drugs were separately paired with bortezomib—originally Takeda’s Velcade—and the steroid dexamethasone.

Previously, DREAMM-7 had met its primary endpoint of progression-free survival, showing the Blenrep-Vd combo significantly slashed the risk of progression or death by 59% compared with Darzalex-Vd. At the time of that analysis, GSK was optimistic that Blenrep would eventually deliver a survival win, as a preliminary 43% death-risk reduction looked promising to the drugmaker.

Following the initial DREAMM-7 readout and another positive phase 3 readout from the DREAMM-8 trial that’s pitting Blenrep against Velcade in their respective combinations with Bristol Myers Squibb’s Pomalyst and dexamethasone (Pd), also in the second-line setting, GSK last year rekindled its hope that Blenrep could reach 3 billion pounds ($3.8 billion) in peak sales.

At that time, GSK’s chief commercial officer, Luke Miels, said the number was mainly based on potential utilization of the drug as a second-line therapy. The British pharma is also planning to start a new phase 3 trial by the end of 2024 to test Blenrep in patients with newly diagnosed myeloma who are ineligible for stem cell transplants.

During a Thursday call, Miels told reporters that the new overall survival win does not change the 3 billion pound estimate, as the drug has performed in line with GSK’s expectations. But the number could go up if Blenrep succeeds in the first-line setting, he said.

As for the first-line program, Miels said it may involve two separate studies, one for Blenrep in a triplet regimen and the other a quadruplet. In September, Sanofi won an FDA approval for Sarclisa, a direct competitor to Darzalex, to be used in tandem with bortezomib, lenalidomide and dexamethasone in first-line, transplant-ineligible myeloma. And J&J is seeking a rival nod for Darzalex. 

These developments mark a comeback for Blenrep, which was withdrawn from global markets as a late-line therapy in 2022 after failing as a monotherapy in a phase 3 trial. Based on DREAMM-7 and DREAMM-8, GSK has filed Blenrep in the U.S. and EU, among other territories, for approvals in previously treated multiple myeloma.

The question now shifts to the magnitude of Blenrep’s overall survival benefit and how it fares against J&J and Legend Biotech’s CAR-T therapy Carvykti. Both meds target BCMA. In the phase 3 CARTITUDE-4 trial, Carvykti significantly cut the risk of death by 45% compared with PVd or Darzalex-Pd in a similar second-line-plus setting.

Full results from DREAMM-7 will be presented at the upcoming American Society of Hematology meeting in December, GSK said.

Still, it’ll be difficult to make cross-trial comparisons given the different regimens in the trials’ comparator arms. Patients’ underlying characteristics are naturally also not the same between the studies.

As an off-the-shelf therapy, Blenrep will be more easily accessible than Carvykti, even though the latter is a one-time treatment. During a press briefing last year, GSK’s Miels highlighted the fact that CAR-T therapies are only available at a few specialized treatment centers, whereas about 70% of myeloma patients are treated in the community setting.

Looking forward, Blenrep might eventually also have to face bispecific antibodies such as J&J’s Tecvayli and Pfizer’s Elrexfio. Miels has touted Blenrep’s easier-to-manage safety profile as an advantage in those potential matchups. The T-cell engagers are linked to potentially dangerous immune and neuro side effects, while Blenrep’s most notable tolerability problem is eye toxicity. 

During Thursday’s press call, Miels said GSK already has a good handle on adjusting Blenrep’s dosing to manage the blurred vision problem.