Global pharma powerhouse Bristol Myers Squibb has secured accelerated US approval for ZENBEXUS (iberdomide), opening the door to a new class of targeted therapies for patients with multiple myeloma after at least one prior line of treatment.

 

FDA nod to ZENBEXUS -- the first approved cereblon-modulating protein degrader (CELMoD) -- in combination with daratumumab and hyaluronidase-fihj and dexamethasone (ZDd) came in the wake of results from Phase 3 EXCALIBER-RRMM trial.

 

At a median follow-up of 16 months, 41% of patients receiving ZDd achieved an MRD-negative complete response, compared with 21% receiving daratumumab, bortezomib and dexamethasone (DVd).

 

“...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 programs,” said Cristian Massacesi, chief medical officer and head of development at Bristol Myers Squibb. 

 

'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.”

 

CELMoDs are designed to build on the biology of immunomodulatory drugs by modulating the cereblon protein and driving targeted protein degradation.

 

For BMS, the approval represents a major step in its broader targeted protein degradation strategy, an area in which the company has invested for more than two decades.

 

“The FDA approval of iberdomide marks the anticipated arrival of a new therapeutic class for relapsed or refractory multiple myeloma and has the potential to make a meaningful difference for patients,” said Sagar Lonial, lead investigator and chief medical officer of the Winship Cancer Institute of Emory University. 

 

'The strong results observed with the CELMoD-based combination within a familiar triplet approach creates the potential for a new treatment foundation in multiple myeloma.”

 

The EXCALIBER-RRMM study enrolled patients with relapsed or refractory multiple myeloma who had received one to two prior lines of therapy. A total of 939 patients were randomized, with the primary MRD-negativity efficacy analysis based on the first 420 patients enrolled in the relevant treatment groups.

 

The trial continues to evaluate progression-free survival (PFS), its other dual primary endpoint. BMS said full EXCALIBER-RRMM data are expected later this year.

 

In the EXCALIBER-RRMM study, serious adverse reactions occurred in 58.3% of patients receiving ZENBEXUS. Fatal adverse reactions occurred in 10 patients, or 4.9%.

 

Neutropenia was particularly common, occurring in 90.2% of patients receiving the ZENBEXUS combination, while infections occurred in 78.9%. Serious infections occurred in 40% of patients.

 

The most common adverse reactions included upper respiratory tract infection, fatigue, musculoskeletal pain, pneumonia, diarrhea, motor dysfunction, rash, sleep disorders, hypogammaglobulinemia, COVID-19 and constipation.

 

Venous thromboembolic events occurred in 6.4% of patients despite mandatory thromboprophylaxis, while arterial thromboembolic events occurred in 3.4%.

 

For patients and clinicians, the approval expands treatment choices at a critical point in the course of multiple myeloma.

 

“The goal for every person living with multiple myeloma is not simply to live longer, but to live well,” said Heather Cooper Ortner, president and chief executive officer of the International Myeloma Foundation. 

 

“This approval represents an important step forward by expanding treatment options for patients facing their first relapse. Every new option gives patients and their healthcare teams additional choices as treatment needs evolve, as well as renewed hope for the future.”