Bexobrutideg Gains FDA Orphan Drug Status in Waldenström Macroglobulinemia
Bexobrutideg, a first-in-class Bruton’s tyrosine kinase degrader, has been granted orphan drug designation from the FDA in Waldenström macroglobulinemia.
US FDA
- The FDA granted bexobrutideg (NX-5948) orphan drug designation for the treatment of patients with Waldenström macroglobulinemia.
- Bexobrutideg is an orally bioavailable, brain penetrant, Bruton tyrosine kinase(BTK) degrader that previously received fast track designation from the FDA.
- A phase 1a/b NX-5948-301 trial (NCT05131022) is currently evaluating bexobrutideg for the treatment of adult patients with relapsed/refractory B-cell malignancies.
The FDA has granted and orphan drug designation to bexobrutideg, a first-in-class BTK degrader, for the potential treatment of patients with Waldenström macroglobulinemia.1
An ongoing phase 1a/b trial titled NX-5948-301 is currently evaluating bexobrutideg in adult patients with relapsed/refractory B-cell malignancies.2
“The FDA’s orphan drug designation for bexobrutideg…represents an important milestone in our regulatory strategy and underscores the significant unmet medical need for improved treatments for Waldenström macroglobulinemia,” said Arthur T. Sands, MD, PhD, president and chief executive officer of Nurix, in a press release.1 “Granting of the designation highlights bexobrutideg’s potential to provide patients with Waldenström macroglobulinemia a promising new therapeutic option. We are also pleased to announce that our investigational therapy bexobrutideg has been assigned a nonproprietary name reflecting its novel mechanism of action, designated with the unique suffix “deg” for degrader.”
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Bexobrutideg, an investigational, orally bioavailable, brain penetrant, small molecule degrader of BTK, previously showed encouraging safety and efficacy data and early promise of clinical benefit when used as a treatment for patients with Waldenström macroglobulinemia. Early findings from the phase 1a/b trial also showed there to be potential for durable outcomes with bexobrutideg.
In December 2024, the agent was granted fast track designation from the FDA for the treatment of adult patients with relapsed/refractory Waldenström macroglobulinemia who received 2 or more lines of therapy, including a BTK inhibitor.2 In addition to Waldenström macroglobulinemia, bexobrutideg is also being developed for the potential treatment of inflammatory diseases.1
“We are excited that bexobrutideg has been recognized by the USAN Council as a unique entity and member of a new class of small molecule drugs, targeted protein degraders,” said Gwenn Hansen, PhD, chief scientific officer of Nurix, in the press release.1 “The catalytic mechanism of action and event driven pharmacology triggering ubiquitination and proteasomal degradation of a target protein is highly differentiated from inhibitors and allows degraders to eliminate the totality of a protein’s function. In our BTK degrader clinical program, we have also established that degraders can eliminate mutant oncoproteins that have proven to be resistant to inhibitor therapy.”
About the Phase 1a/b Trial of Bexobrutideg
The first-in-human, multicenter, open-label, phase 1a/1b trial is examining the safety and anti-cancer activity of bexobrutideg in patients with advanced B-cell malignancies.3
The phase 1a, dose-escalation portion of the trial included patients aged 18 years and older with relapsed/refractory Waldenström macroglobulinemia, non-Hodgkin lymphoma, chronic lymphocytic leukemia, or small lymphocytic lymphoma who have received at least 2 prior lines of therapy and have an ECOG performance status of 0 or 1. In this portion of the study, patients were given the agent at escalating doses from 50 mg daily to 600 mg daily.
In phase 1b, the dose-expansion portion, patients with Waldenström macroglobulinemia who have relapsed/refractory disease will be enrolled if they have also received treatment with a prior BTK inhibitor. The efficacy of the agent will be assessed at the dose(s) selected in phase 1a of the study in this portion in up to 7 expansion arms of patients with histologically confirmed relapsed/refractory B-cell malignancy indications who have received the specified prior therapies.
The trial is expected to release more data in 2025.
REFERENCES
Nurix announces U.S. FDA orphan drug designation granted to bexobrutideg (NX-5948) for the treatment of Waldenström macroglobulinemia. News release. Nurix Therapeutics. March 17, 2025. Accessed March 18, 2025. https://tinyurl.com/4vm9s6xd
Nurix Therapeutics receives U.S. FDA fast track designation for NX-5948 for the treatment of relapsed or refractory Waldenstrom’s macroglobulinemia. News release. Nurix Therapeutics. December 19, 2024. Accessed March 18, 2025. https://tinyurl.com/2rkcr75n
A study of NX-5948 in adults with relapsed/refractory B-cell malignancies. ClinicalTrials.gov. Updated March 5, 2025. Accessed March 18, 2025. https://www.clinicaltrials.gov/study/NCT05131022
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