On February 5, 2021, the Food and Drug Administration granted accelerated approval to umbralisib (Ukoniq, TG Therapeutics), a kinase inhibitor including PI3K-delta and casein kinase CK1-epsilon, for the following indications:
- Adult patients with relapsed or refractory marginal zone lymphoma (MZL) who have received at least one prior anti-CD20-based regimen;
- Adult patients with relapsed or refractory follicular lymphoma (FL) who have received at least three prior lines of systemic therapy.
Approval was based on two single-arm cohorts of an open-label, multi-center, multi-cohort trial, UTX-TGR-205 (NCT02793583), in 69 patients with MZL who received at least one prior therapy, including an anti-CD20 containing regimen, and in 117 patients with FL after at least 2 prior systemic therapies. Patients received umbralisib 800 mg orally once daily until disease progression or unacceptable toxicity.
Efficacy was based on overall response rate (ORR) and duration of response (DOR) using modified 2007 International Working Group criteria assessed by an independent review committee.
For patients with MZL, the ORR was 49% (95% CI: 37.0, 61.6) with 16% achieving complete responses. Median DOR was not reached (95% CI: 9.3, NE) in these patients. For patients with FL, the ORR was 43% (95% CI: 33.6, 52.2) with 3% achieving complete responses. Median DOR was 11.1 months (8.3, 16.4).
The most common (>15%) adverse reactions, including laboratory abnormalities, were increased creatinine, diarrhea-colitis, fatigue, nausea, neutropenia, transaminase elevation, musculoskeletal pain, anemia, thrombocytopenia, upper respiratory tract infection, vomiting, abdominal pain, decreased appetite, and rash. Serious adverse reactions occurred in 18% of patients, most often from diarrhea-colitis and infection. Diarrhea-colitis and transaminase elevation were the most common reasons for dose modifications.
The prescribing information provides warnings and precautions for adverse reactions including infections, neutropenia, diarrhea and non-infectious colitis, hepatotoxicity, and severe cutaneous reactions.
The recommended umbralisib dose is 800 mg taken orally once daily with food until disease progression or unacceptable toxicity.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
This application was granted priority review for the MZL indication and orphan drug designation was granted for the treatment of MZL and FL. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.
The MZL and FL indications were granted accelerated approval based on overall response rate. Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.
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