Bexobrutideg Receives Orphan Drug Designation in Waldenström Macroglobulinemia

Bexobrutideg, an oral BTK degrader, received orphan drug designation from the FDA for Waldenström macroglobulinemia, following promising phase 1 trial results.

The orally bioavailable agent bexobrutideg (NX-5948) was granted Orphan drug designation by the U.S. Food and Drug Administration (FDA) for the treatment of Waldenström macroglobulinemia (WM), a rare type of non-Hodgkin's lymphoma, according to a news release from Nurix Therapeutics, Inc., and is being evaluated in an ongoing phase 1a/b clinical trial in adult patients with relapsed or refractory B-cell malignancies.

Orphan drug designation is a status granted by the U.S. FDA to drugs and biologics intended to treat rare diseases or conditions, according to the official FDA website, fda.gov, which noted that the regulatory designation is a separate process from seeking approval or licensing.

The news release went on to state that the regulatory decision follows phase 1 trial data which evaluated the first-in-class Bruton’s tyrosine kinase (BTK) degrader which were shared at the 12th International Workshop on Waldenström Macroglobulinemia.

“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. 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,” Dr. Gwenn Hansen, chief scientific officer of Nurix, stated in the news release. “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.”

WM is a rare, slow-growing type of non-Hodgkin lymphoma which occurs when abnormal white blood cells take over the bone marrow, reducing the number of healthy blood cells. This can lead to anemia, increased risk of bleeding and a weakened immune system. Additionally, high levels of a protein called IgM, produced by these abnormal cells, can cause nerve-related symptoms.

In the United States, WM affects approximately 1,200 to 1,900 people each year, with an estimated 12,000 to 19,000 people currently living with the disease. The condition typically progresses over about 10 years. First-line treatment options include chemoimmunotherapy and BTK inhibitor therapy. However, there are currently no approved treatments for patients whose disease progresses after this therapy.

More Information on the Regulatory Decision and Agent Under Investigation

The investigational, orally bioavailable, brain penetrant, small molecule degrader of BTK is currently being evaluated in a phase 1 clinical trial for patients with relapsed or refractory B cell malignancies. Because Nurix has already reported encouraging safety and efficacy data for patients with WM who were treated in the ongoing phase 1a/b clinical trial of bexobrutideg, the company continues to enroll patients with WM onto an ongoing phase 1b expansion cohort of the study. These previous reports of data demonstrated early clinical benefit with treatment, which has the potential for durable outcomes, according to the news release.

The phase 1a portion of the study will determine the safest dose of bexobrutideg and how well patients tolerate it, according to the official trial’s informational page on clinicaltrials.gov. This phase includes adults with relapsed or treatment-resistant B-cell cancers who have already received at least two prior treatments, and have no other effective treatment options available. In the first part of the phase 1b trial, known as the safety expansion phase, researchers will further evaluate the safety of the agent and assess its effectiveness in slowing or shrinking tumors. Contrarily, in the second part of the phase 1b trial, known as the cohort expansion portion, investigators will continue to assess how well bexobrutideg works at the dose determined in the earlier phase.

In 2025, additional clinical data is expected to be shared.

“The FDA’s orphan drug designation for bexobrutideg, also known as NX-5948, represents an important milestone in our regulatory strategy and underscores the significant unmet medical need for improved treatments for [WM],” Dr. Arthur T. Sands, president and chief executive officer of Nurix, concluded in the news release “Granting of the designation highlights bexobrutideg’s potential to provide patients with WM 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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