The US Food and Drug Administration (FDA) has granted accelerated approval to Bristol Myers Squibb’s (BMS) Zenbexus (iberdomide), along with daratumumab and hyaluronidase-fihj and dexamethasone (ZDd), to treat adult multiple myeloma (MM) 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 said to be the first cereblon E3 ligase modulator (CELMoD) therapy approved by the FDA for MM treatment. Continued approval for this indication may depend on confirmation of clinical benefit in ongoing trials.
In combination with ZDd, Zenbexus received the agency’s decision following results from the Phase III EXCALIBER-RRMM trial.
The study compared Zenbexus, ZDd (n=207) with daratumumab, bortezomib and dexamethasone (n=213) in patients with relapsed or refractory MM.
After a median follow-up of 16 months, 41% of patients treated with ZDd achieved minimal residual disease (MRD)-negative complete response compared to 21% receiving the comparator regimen.
Safety data indicated that 7.8% of patients discontinued ZDd because of adverse reactions.
Serious infections and severe neutropenia were observed, with neutropenia and infections occurring in 90.2% and 78.9% of patients, respectively.
Fatal adverse reactions occurred in 4.9% of patients treated with Zenbexus, with sepsis as the only event affecting more than one individual. Other observed reactions included upper respiratory tract infection, pneumonia, diarrhoea and fatigue.
Bristol Myers Squibb chief medical officer and development head Cristian Massacesi said: “Today’s approval of Zenbexus represents meaningful progress for patients living with multiple myeloma and underscores the power of our targeted protein degradation platform, particularly our CELMoD programmes.
“As the first approved CELMoD, Zenbexus marks the arrival of a new treatment class and is an important milestone in our efforts to expand what is possible for patients with multiple myeloma. And we believe this is only the beginning.
“This approval validates years of scientific research and strengthens our confidence in the potential of this approach as we continue to advance our innovative pipeline on behalf of patients with significant unmet needs.”
This review was conducted under the FDA’s Project Orbis, enabling concurrent regulatory assessment in several other countries.
