The Food and Drug Administration (FDA) has granted accelerated approval to Ukoniq (umbralisib; TG Therapeutics), for the treatment of adults with relapsed or refractory marginal zone lymphoma (MZL) who have received at least 1 prior anti-CD20-based regimen; and in adults with relapsed or refractory follicular lymphoma (FL) who have received at least 3 prior lines of systemic therapy.
Ukoniq is the first oral inhibitor of phosphoinositide 3 kinase (PI3K) delta and casein kinase 1 (CK1) epsilon. PI3K delta is expressed in normal and malignant B-cells; CK1 epsilon has been implicated in the pathogenesis of cancer cells, including lymphoid malignancies.
The approval was based on data from the open-label, multi-cohort phase 2 UNITY-NHL Trial (Clinicaltrials.gov: NCT02793583), which included a total of 69 patients with MZL, who received at least 1 prior therapy, including an anti-CD20 containing regimen, and 117 patients with FL who received at least 2 prior systemic therapies, including an anti-CD20 monoclonal antibody and an alkylating agent. The primary end point was overall response rate (ORR) as assessed by an independent review committee (IRC) according to the Revised International Working Group Criteria.
Results showed that the ORR was 49% (95% CI, 37.0-61.6) and 43% (95% CI, 33.6-52.2) in the MZL and FL groups, respectively. In the MZL group, 16% and 33% of patients achieved complete and partial responses, respectively, with a median duration of response that was not reached (95% CI, 9.3-NR). In the FL group, 3.4% and 39% of patients achieved complete and partial responses, respectively, with a median duration of response of 11.1 months (95% CI, 8.3-16.4). Continued approval may be based on a confirmatory trial.
Serious adverse reactions that occurred in 2% or more of patients, were diarrhea-colitis, pneumonia, sepsis, and urinary tract infection. The most common adverse reactions (incidence greater than or equal to 15%) were increased creatinine, diarrhea-colitis, fatigue, nausea, neutropenia, ALT increase, AST increase, musculoskeletal pain, anemia, thrombocytopenia, upper respiratory tract infection, vomiting, abdominal pain, decreased appetite, and rash.
Ukoniq is supplied as 200mg strength tablets in 120 count bottles. According to the Company, commercial launch is underway.
- TG Therapeutics announces FDA accelerated approval of Ukoniq™ (umbralisib). [press release]. New York, NY; TG Therapeutics: February 5, 2021.
- Ukoniq [package insert]. New York, NY: TG Therapeutics, 2021.