The US Food and Drug Administration (FDA) has granted accelerated approval to Bristol Myers Squibb's (BMS) Zenbexus (iberdomide), in combination with daratumumab and hyaluronidase-fihj and dexamethasone (ZDd), for the treatment of adult multiple myeloma patients.

The combination is intended for patients who have previously received at least one line of therapy that included both a proteasome inhibitor and an immunomodulatory agent. 

Zenbexus is the first cereblon E3 ligase modulator (CELMoD) therapy to receive FDA approval for multiple myeloma treatment. 

Continued approval for this indication may depend on verification of clinical benefit in ongoing confirmatory trials.

The review was conducted under the FDA's Project Orbis initiative, which enables concurrent regulatory assessment of the therapy in several other countries.

The approval was based on results from the Phase III EXCALIBER-RRMM trial, which compared Zenbexus plus ZDd (n=207) against daratumumab, bortezomib and dexamethasone (n=213) in patients with relapsed or refractory multiple myeloma.

After a median follow-up of 16 months, 41% of patients treated with the ZDd combination achieved minimal residual disease (MRD)-negative complete response, compared to 21% of patients receiving the comparator regimen.

Safety data showed that 7.8% of patients discontinued ZDd treatment due to adverse reactions. Neutropenia occurred in 90.2% of patients and infections in 78.9%, with serious infections and severe neutropenia observed among trial participants. 

Fatal adverse reactions occurred in 4.9% of patients treated with Zenbexus, with sepsis the only event affecting more than one individual. Other reported reactions included upper respiratory tract infection, pneumonia, diarrhoea and fatigue.

Cristian Massacesi, Chief Medical Officer and Development Head at Bristol Myers Squibb, said the approval of Zenbexus represents meaningful progress for patients living with multiple myeloma and underscores the strength of the company's targeted protein degradation platform, particularly its CELMoD programmes.

Massacesi noted that as the first approved CELMoD, Zenbexus marks the arrival of a new treatment class and an important milestone in the company's efforts to expand treatment possibilities for multiple myeloma patients, adding that the company views this as only the beginning.