Nurix Therapeutics, Inc. (Nasdaq: NRIX) has announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to NX-5948, a highly selective degrader of Bruton’s tyrosine kinase (BTK), for the treatment of adult patients with relapsed or refractory Waldenstrom’s macroglobulinemia (WM) after at least two lines of therapy, including a BTK inhibitor. This designation aims to expedite the development and review of the drug, addressing a critical unmet need in patients whose cancer has progressed despite prior BTK inhibitor treatment. The company's stock has shown remarkable strength, delivering a 104% return over the past year.
Arthur T. Sands, M.D., Ph.D., president and chief executive officer of Nurix, stated, “Fast Track designation for NX-5948 is an important recognition of the unmet patient need in Waldenstrom’s macroglobulinemia, particularly in the growing number of patients whose cancer has progressed following BTK inhibitor therapy. This designation follows encouraging safety and efficacy data from our ongoing Phase 1 clinical trial, demonstrating early promise of clinical benefit with potential for durable outcomes. We continue to enroll Waldenstrom’s macroglobulinemia patients in the ongoing Phase 1b expansion cohort and anticipate sharing additional clinical data in 2025.”
Addressing Unmet Needs in Waldenstrom's Macroglobulinemia
Waldenstrom’s macroglobulinemia (WM) is a rare, slow-growing type of non-Hodgkin’s lymphoma characterized by the replacement of normal bone marrow cells by malignant lymphocytic cells that produce monoclonal IgM. This leads to anemia, bleeding, and impaired immune function, with elevated IgM levels potentially causing neurologic symptoms. The incidence of WM ranges from 0.36 to 0.57 per 100,000 people in the United States, affecting approximately 12,000 to 19,000 patients. While first-line treatments include chemoimmunotherapy and BTK inhibitors, there are currently no approved therapies for WM patients after BTK inhibitor failure.
NX-5948: A Novel BTK Degrader
NX-5948 is an investigational, orally bioavailable, brain-penetrant small molecule designed to degrade BTK, a key protein in B-cell malignancies. By selectively eliminating BTK, NX-5948 aims to overcome resistance mechanisms associated with current BTK inhibitors. Nurix has reported that NX-5948 is highly potent against tumor cell lines resistant to existing BTK inhibitor therapies, making it a promising candidate for heavily pretreated CLL/SLL patient populations.
Regulatory Designations and Clinical Development
In addition to the Fast Track designation for WM, NX-5948 previously received Fast Track designation in January 2024 for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) after at least two lines of therapy, including a BTK inhibitor and a B-cell lymphoma 2 (BCL2) inhibitor. Furthermore, in November 2024, the European Medicines Agency (EMA) granted NX-5948 PRIME designation for the treatment of adult patients with relapsed or refractory CLL/SLL after at least a BTK inhibitor and a BCL2 inhibitor.
NX-5948 is currently being evaluated in a Phase 1 clinical trial (NCT05131022) in patients with relapsed or refractory B-cell malignancies. The ongoing Phase 1b expansion cohort is enrolling Waldenstrom’s macroglobulinemia patients, with additional clinical data expected in 2025. Preliminary data presented at the 12th International Workshop on Waldenstrom’s Macroglobulinemia demonstrated an objective response rate of 77.8% (7 of 9 patients) among WM patients treated with NX-5948.
Implications of Fast Track Designation
The FDA's Fast Track designation is intended to facilitate and expedite the development and review of drug candidates that treat serious conditions and fulfill an unmet medical need. This designation allows for more frequent interactions with the FDA to discuss the candidate's development plan and, if relevant criteria are met, eligibility for Accelerated Approval and Priority Review.
