General Information

The FDA withdrew approval of Ukoniq in June of 2022 following a safety review showing an increased risk of death in patients taking Ukoniq.

Ukoniq (umbralisib) is a kinase inhibitor. 

Ukoniq is specifically indicated for the treatment of adult patients with relapsed or refractory marginal zone lymphoma (MZL) who have received at least one prior anti-CD20-based regimen and for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL) who have received at least three prior lines of systemic therapy.

Ukoniq is supplied as a tablet for oral administration. The recommended dosage of Ukoniq is 800 mg taken orally once daily with food until disease progression or unacceptable toxicity. The tablets should be swallowed whole. Do not crush, break, cut, or chew tablets. Ukoniq should be taken at the same time each day. If vomiting occurs, do not take an additional dose; continue with the next scheduled dose. If a dose is missed, take a missed dose unless it is less than 12 hours until the next scheduled dose.

Mechanism of Action

Ukoniq (umbralisib) is an oral inhibitor of phosphoinositide 3 kinase (PI3K) delta and casein kinase 1 (CK1) epsilon. PI3K-delta is known to play an important role in supporting cell proliferation and survival, cell differentiation, intercellular trafficking and immunity and is expressed in both normal and malignant B-cells. CK1-epsilon is a regulator of oncoprotein translation and has been implicated in the pathogenesis of cancer cells, including lymphoid malignancies. 

Side Effects

Adverse effects associated with the use of Ukoniq may include, but are not limited to, the following:

• laboratory abnormalities: increased creatinine
• diarrhea-colitis
• fatigue
• nausea
• neutropenia
• transaminase elevation
• musculoskeletal pain
• anemia
• thrombocytopenia
• upper respiratory tract infection
• vomiting
• abdominal pain
• decreased appetite
• rash

Clinical Trial Results

Ukoniq for the treatment of MZL and FL was granted accelerated approval by the FDA based on overall response rate in clinical studies. Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

The efficacy of Ukoniq monotherapy was evaluated in two single-arm cohorts within the Phase 2 UNITY-NHL clinical trial, an open-label, multi-center, multi-cohort study with patients receiving Ukoniq 800 mg once daily. The MZL cohort included 69 patients who received at least 1 prior therapy, including an anti-CD20 regimen. The FL cohort included 117 patients who received at least 2 prior systemic therapies, including an anti-CD20 monoclonal antibody and an alkylating agent. The primary endpoint was independent review committee (IRC) assessed overall response rate (ORR) according to the Revised International Working Group Criteria. The ORR in the MZL arm was 49% and the ORR in the FL arm was 43%.