Novel BTK Degrader Earns FDA Fast Track Designation in CLL/SLL

• The FDA has granted fast track designation to BGB-16673 for patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
• BGB-16673 is an oral Bruton tyrosine kinase (BTK)-targeting chimeric degradation activation compound (CDAC).
• Fast track designation is intended to facilitate the development and review of drugs that fill serious unmet medical needs.

BGB-16673, an orally available BTK-targeting CDAC, has been granted FDA fast track designation for patients with R/R CLL or SLL who have been treated with at least 2 prior lines of therapy.¹

FDA fast track designation is intended to facilitate the development and expedite the review of drugs for serious conditions that fill unmet medical needs. With this designation, BeiGene, the sponsor, will be eligible for more frequent meetings and communication with the FDA, as well as accelerated approval and priority review if certain criteria are met.

“When disease progression for patients on BTK inhibitors occurs, there is a need for BTK-targeting agents with a different mode of action given the centrality of this pathway in CLL/SLL. BTK-protein degradation with our BTK CDAC (BGB-16673) may address this unmet need,” said Mehrdad Mobasher, MD, MPH, chief medical officer, hematology, at BeiGene, in a press release. “The FDA’s fast track designation supports our goal of efficiently developing BGB-16673 for these patients, the first investigational drug from our CDAC platform.”

The designation is supported by a phase 1/2 study (NCT05006716). Preliminary efficacy and safety findings were presented at the 2024 European Hematology Association (EHA) Congress.² Here, the overall response rate (ORR) was 67% among 24 response-evaluable patients. The maximum tolerated dose was not observed, and 1 patient experienced a dose-limiting toxicity at the 200-mg dose. Responses were seen at the lowest dose level of 50 mg.

One patient at the 500-mg dose had a treatment-emergent adverse event (TEAE) of grade 3 hypertension, and 2 patients had TEAEs that led to death but were considered unrelated to treatment. The most common TEAEs were contusion (grade 1/2, 31%; no grade ≥3), fatigue (grade 1/2, 31%; no grade ≥3), diarrhea (grade 1/2, 26%; no grade ≥3), and neutropenia (grade 1/2, 31%; grade ≥3 18%). Overall, the treatment was well tolerated.

“We believe BGB-16673 strengthens our hematology leadership and complements [zanubrutinib (Brukinsa)] the backbone for our investigational hematology pipeline. BGB-16673 is the most advanced BTK degrader in the clinic and is well-suited to become an important therapy for patients progressing after BTK [inhibitors] who have limited options,” added Mobasher in the press release.¹

REFERENCES:

1. BeiGene’s BGB-16673 receives U.S. FDA fast track designation for CLL/SLL. News release. BeiGene, Ltd. August 26, 2024. Accessed August 26, 2024. https://tinyurl.com/3kskc2vj

2. Parrondo R, Thompson M, Frustaci AM, et al. Preliminary efficacy and safety of the Bruton tyrosine kinase (BTK) degrader BGB-16673 in patients with relapsed or refractory (R/R) CLL/SLL: results from the phase 1 BGB-16673-01 study. Presented at: 2024 European Hematology Association Hybrid Congress; June 13-June 16, 2024; Madrid, Spain. Abstract S157.