FDA Extends PDUFA Date for Ublituximab Plus Umbralisib BLA and sNDA in CLL/SLL

Following a submission of updated survival data, the FDA has extended the Prescription Drug User Fee Act date for ublituximab/umbralisib in chronic lymphocytic leukemia and small lymphocytic lymphoma.

The FDA has decided to extend the Prescription Drug User Fee Act (PDUFA) date for the ublituximab/umbralisib (U2; Ukoniq) biologics license application (BLA) and supplemental new drug application for chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) to June 25, 2022, according to a press release from developer TG Therapeutics.1

The company had submitted data from an updated overall survival (OS) analysis to the FDA on February 2022. The submission constituted a major amendment to the applications, prompting the FDA to extend the PDUFA date to allow for a full review of the submissions.

“As mentioned on our earnings call earlier this week, we believed an extension of the PDUFA date was a likely scenario especially given the proposed timing of the upcoming ODAC [Oncologic Drugs Advisory Committee] meeting. We hope this extension provides the time needed to give proper attention and review to the U2 BLA/sNDA. We continue to believe in the potential of U2 to provide a meaningful treatment option to patients with CLL and SLL,” Michael S. Weiss, chairman and chief executive officer at TG Therapeutics, said in the press release.

In particular, the FDA raised questions for the ODAC meeting, including the risk-benefit of U2 in CLL/SLL and relapsed/refractory marginal zone lymphoma or follicular lymphoma. Part of the risk-benefit analysis will review adverse effects (AEs), discontinuations because of AEs, and dose modifications.

In February 2022, the FDA placed a partial clinical hold on all trials of U2 in patients with CLL and non-Hodgkin lymphoma after concerns arose from an early OS analysis of the UNITY-CLL trial.2

OS was a secondary efficacy outcome, and was not included in the primary analysis; as such, it wasn’t included in the BLA or sNDA. Also of note, the trial was not powered for OS. Due to this, the FDA requested early OS analysis from the trial as part of the ongoing BLA and sNDA review.

Important, as of the cut-off date of September 2021, a non-statistically significant imbalance was observed that favored the control arm (HR, 1.23). When deaths related to COVID-19 were excluded, however, the study arms appeared balanced with no statistically significant OS differences between the cohorts (HR, 1.04).

Previous findings from the phase 3 UNITY-CLL trial (NCT02612311) prespecified interim analysis indicated that the primary end point of statistically significantly improved progression-free survival (PFS) had been met (P <.0001).3 At the time the study read out, the trial was stopped due to the superior efficacy. PFS benefit by independent review committee was observed in patients who were previously untreated or refractory.


  1. TG Therapeutics announces extension of U.S. FDA BLA/sNDA PDUFA date for ublituximab plus UKONIQ® (U2) to treat patients with CLL and SLL. News release. TG Therapeutics. March 3, 2022. Accessed March 3, 2022. https://bit.ly/3tp7wbn
  2. TG Therapeutics falls 30% as CEO discloses partial clinical hold on blood cancer trials. News release. TG Therapeutics. January 28, 2022. Accessed March 3, 2022. https://yhoo.it/3rWhKPL
  3. TG Therapeutics announces positive topline results from the UNITY-CLL phase 3 study evaluating the combination of umbralisib and ublituximab (U2) for the treatment of patients with chronic lymphocytic leukemia. News release. TG Therapeutics. May 5, 2020. Accessed March 3, 2022. https://bit.ly/3HEoCXZ