Bristol Myers Squibb may be leading the way when it comes to pursuing cereblon E3 ligase modulator (CELMoD) drugs, but today the pharma is standing tall.
BMS shared data at the American Society of Clinical Oncology annual meeting Friday that demonstrated that its CELMoD candidate mezigdomide more than doubled progression-free survival in patients with relapsed or refractory multiple myeloma.
The data come from the 479 patients analyzed in the phase 3 SUCCESSOR-2 trial testing mezigdomide in combination with Amgen’s Kyprolis and dexamethasone versus that pair alone.
Patients in the mezigdomide arm lived without disease progression for an average of 18 months, compared to 8.3 months for those given just Kyprolis and dexamethasone. Overall, the mezigdomide regimen cut the risk of disease progression or death by 52%, BMS reported in a May 29 release.
The pharma had previously announced that the trial hit its primary endpoint of progression-free survival, but is only now divulging the numbers behind the win.
“It’s incredibly exciting,” Anne Kerber, M.D., BMS’ head of late-stage development for hematology, oncology and cell therapy, told Fierce Biotech in an interview ahead of ASCO. Kerber highlighted the fact that mezigdomide managed to nearly triple the complete response rate to 26.7% compared to 8.9% in the control arm, despite patients in the study being heavily pretreated.
It’s still too early to draw conclusions about overall survival rates, Kerber added, but so far it seems like mezigdomide is having an effect there too.
“The overall survival data is immature, but we already start [to] see the curves separate at this very early point in time,” she told Fierce.
Side effects were worse in patients treated with mezigdomide, with 83.7% of patients reporting grade 3 or 4 adverse events related to treatment in the mezigdomide arm vs 56.5% in the control cohort. This safety profile is consistent with prior trials, according to Kerber, and side effects were “nothing unexpected and very well manageable.”
BMS plans to discuss the data with the FDA at some point in the future, Kerber said. The regulator is already considering another of the drugmaker’s CELMoD candidates, iberdomide, for approval in the same indication, with a decision expected by August 17.
CELMoD drugs, which have not yet had an FDA approval, are similar to the pharma’s approved protein degraders thalidomide, Revlimid and Pomalyst. In multiple myeloma, they are designed to target transcription factors called Ikaros and Aiolos, which the cancer relies on.
“These compelling data further validate our targeted protein degradation platform, and cereblon as a critical therapeutic target in multiple myeloma,” Cristian Massacesi, M.D., BMS’ chief medical officer and head of development, said in the release.
“Mezigdomide is a very potent, oral CELMoD and we’re committed to bringing it forward as a potential new standard of care for relapsed/refractory multiple myeloma across multiple settings,” Massacesi added.
Kerber highlighted to Fierce that some of the patients in the SUCCESSOR-2 study had been previously treated with Revlimid and Pomalyst, but mezigdomide still worked. Mezigdomide is also more potent than iberdomide, but the two pair differently with existing medications, leaving room for both in the myeloma care landscape.
Though mezigdomide development is for now focused on later lines of therapy, Kerber said BMS hopes to bring the molecule forward in the treatment paradigm in the same way iberdomide has been.
“The concept in multiple myeloma is really to bring up your best treatments into as early [line] as possible, to really drive very long progression-free survival times,” Kerber said.
Meanwhile, another CELMoD drug, golcadomide, is in the works for patients newly diagnosed with B-cell lymphoma, with fresh data also being shared at this month’s ASCO event.
