On 5 February 2021, the US Food and Drug Administration (FDA) granted accelerated approval to umbralisib (Ukoniq, TG Therapeutics), a kinase inhibitor including PI3K-delta and casein kinase CK1-epsilon, for the following indications:<\/p>\n
Approval was based on two single-arm cohorts of an open-label, multi-centre, multi-cohort study, 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. <\/p>\n
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.<\/p>\n
For patients with MZL, the ORR was 49% (95% confidence interval [CI] 37.0, 61.6) with 16% achieving complete responses. Median DoR was not reached (95% CI 9.3, NE) in these patients.<\/p>\n
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).<\/p>\n
The most common (><\/u>15%) adverse reactions, including laboratory abnormalities, were increased creatinine, diarrhoea-colitis, fatigue, nausea, neutropenia, transaminase elevation, musculoskeletal pain, anaemia, thrombocytopenia, upper respiratory tract infection, vomiting, abdominal pain, decreased appetite, and rash. Serious adverse reactions occurred in 18% of patients, most often from diarrhoea-colitis and infection. Diarrhoea-colitis and transaminase elevation were the most common reasons for dose modifications.<\/p>\n
The prescribing information provides warnings and precautions for adverse reactions including infections, neutropenia, diarrhoea and non-infectious colitis, hepatotoxicity, and severe cutaneous reactions.<\/p>\n
The recommended umbralisib dose is 800 mg taken orally once daily with food until disease progression or unacceptable toxicity.<\/p>\n
Full prescribing information for Ukoniq is available here<\/a>.<\/p>\n This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA\u2019s assessment.<\/p>\n This application was granted priority review for the MZL indication and orphan drug designation was granted for the treatment of MZL and FL.<\/p>\n The MZL and FL indications were granted accelerated approval based on ORR. Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials.<\/p>\n Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA\u2019s MedWatch Reporting System.<\/p>\n For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact FDA\u2019s Oncology Center of Excellence<\/a> Project Facilitate<\/a>.<\/p>\n