{"entity":{"id":"umbralisib","kind":"drug","name":"Umbralisib","aka":[],"tldr":"A PI3K inhibitor for marginal zone and follicular lymphoma approved in 2021 and withdrawn in 2022 after the UNITY-CLL trial suggested more deaths.","summary":"Umbralisib is an oral inhibitor of PI3K-delta and casein kinase 1 epsilon, designed to retain the B-cell activity of the class while reducing its immune-mediated toxicities such as colitis and hepatitis. In UNITY-NHL, response rates were around 45 to 50% in relapsed marginal zone and follicular lymphoma, and the FDA granted accelerated approval in February 2021. The UNITY-CLL trial, which combined umbralisib with ublituximab, suggested a possible overall-survival detriment in the experimental arm. TG Therapeutics withdrew the drug in 2022 and the FDA revoked the approval. The episode contributed to the FDA's broader 2022 review of PI3K inhibitors in blood cancers. Umbralisib illustrates why accelerated approvals depend on confirmatory data: a good response rate did not translate into patients living longer.","status":"withdrawn","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Umbralisib","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Umbralisib"}],"tags":["gap-fill"],"related":[],"cancers":["follicular-lymphoma","cll"],"sections":[],"technologies":["kinase-inhibitors"],"targets":["pik3ca"],"drugs":[],"companies":["tg-therapeutics"],"institutions":[],"pathways":["pi3k-akt-mtor"],"terms":[],"trials":["nct03801525","nct02793583","nct04624633"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Ukoniq","modality":"Oral PI3Kδ / CK1ε inhibitor","mechanism":"PI3K delta inhibition with casein kinase 1 epsilon inhibition, intended to reduce immune-mediated toxicity of the class.","approvals":[{"region":"US","year":2021,"indication":"Relapsed marginal zone lymphoma and follicular lymphoma","note":"Withdrawn 2022"}],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[{"date":"2021-02-05","type":"accelerated-approval","region":"US","note":"Accelerated approval on a surrogate endpoint, with a confirmatory trial required.","indication":"Adult patients with relapsed or refractory marginal zone lymphoma (MZL) who have received at least one prior anti-CD20- based regimen"},{"date":"2021-02-05","type":"accelerated-approval","region":"US","note":"Accelerated approval on a surrogate endpoint, with a confirmatory trial required.","indication":"Adult patients with relapsed or refractory follicular lymphoma (FL) who have received at least three prior lines of systemic therapy"},{"date":"2022-05-31","type":"withdrawal","region":"US","note":"Withdrawn: the indication came off the label 1.3 years after its accelerated approval.","indication":"Adult patients with relapsed or refractory marginal zone lymphoma (MZL) who have received at least one prior anti-CD20- based regimen"},{"date":"2022-05-31","type":"withdrawal","region":"US","note":"Withdrawn: the indication came off the label 1.3 years after its accelerated approval.","indication":"Adult patients with relapsed or refractory follicular lymphoma (FL) who have received at least three prior lines of systemic therapy"}]},"route":"/drugs/umbralisib/","neighbours":{"cancer":[{"id":"cll","kind":"cancer","name":"Chronic lymphocytic leukaemia","route":"/cancers/cll/"},{"id":"malt-lymphoma","kind":"cancer","name":"Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma)","route":"/cancers/malt-lymphoma/"},{"id":"follicular-lymphoma","kind":"cancer","name":"Follicular lymphoma","route":"/cancers/follicular-lymphoma/"}],"technology":[{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"target":[{"id":"pik3ca","kind":"target","name":"PIK3CA / PI3K-alpha","route":"/targets/pik3ca/"}],"company":[{"id":"tg-therapeutics","kind":"company","name":"TG Therapeutics","route":"/companies/tg-therapeutics/"}],"pathway":[{"id":"pi3k-akt-mtor","kind":"pathway","name":"PI3K / AKT / mTOR","route":"/pathways/pi3k-akt-mtor/"}],"trial":[{"id":"nct04624633","kind":"trial","name":"Acalabrutinib, Umbralisib, and Ublituximab (AU2) In Relapsed and Untreated CLL","route":"/trials/nct04624633/"},{"id":"nct02793583","kind":"trial","name":"Study to Assess the Efficacy and Safety of Ublituximab + Umbralisib With or Without Bendamustine and Umbralisib Alone in Patients With Previously Treated Non-Hodgkins Lymphoma","route":"/trials/nct02793583/"},{"id":"nct03801525","kind":"trial","name":"Study to Assess the Efficacy and Safety of Ublituximab in Combination With Umbralisib and Venetoclax Compared to Ublituximab in Combination With Umbralisib in Subjects With CLL (ULTRA-V)","route":"/trials/nct03801525/"}],"term":[{"id":"approval-withdrawal","kind":"term","name":"Indication withdrawal","route":"/terms/approval-withdrawal/"}]}}