Umbralisib Developer Seeks FDA Approval In Marginal Zone Lymphoma and Follicular Lymphoma

A rolling submission of a New Drug Application (NDA) for umbralisib (TGR-1202) has been initiated by drug developer, TG Therapeutics, Inc, which is requesting accelerated approval of the agent from the FDA for the treatment of patients with previously treated marginal zone lymphoma (MZL) and follicular lymphoma (FL). The company reported in a press release that one application was considered to be acceptable for both drugs and the NDA will be completed in the first half of 2020.¹

“We are extremely pleased to have initiated our first NDA submission for umbralisib and to have received guidance from the FDA to include both MZL and FL in a single NDA. This is an extremely important milestone for us, as it brings us one step closer to potentially offering a novel treatment option to patients with previously treated MZL and FL,” stated Michael S. Weiss, the executive chairman and chief executive officer of TG Therapeutics. “I want to thank the patients, their families and the research teams who participated in these important trials and helped advance umbralisib, and the TG team for working tirelessly to initiate this NDA submission.”

Umbralisib, a dual inhibitor of PI3K-δ and CK1-ε, is currently being studied in the phase IIb UNITY-NHL study (NCT02793583), which includes subpopulations of patients with MZL and FL. The study is evaluating ublituximab (TGTX-1101) plus umbralisib with or without bendamustine and umbralisib alone as a treatment for patients with previously treated non-Hodgkin lymphoma (NHL).¹

The most recent data show that the study has already met its primary end point of overall response rate in patients with FL. The target ORR was between 40% and 50%, and all patients who were diagnosed with FL (n = 118) met the target.²

Interim data reported in early 2019 showed that responses were also observed in patients with MZL (n = 42). The ORR was 52%, which included a complete response rate of 19% and a partial response rate of 33% (95% CI, 8.4-not reached). Stable disease was not estimated in these patients and the clinical benefit rate was 88%. The efficacy data also showed an 86% reduction in tumor burden in the MZL cohort. The median time to initial response was 2.7 months in these patients. The estimated progression-free survival, the secondary end point of the study, at 12 months was 66%. The median PFS was not reached in this cohort.³

The combination of ublituximab and umbralisib did not result in any unexpected toxicities in patients with MZL. The most common adverse events (AEs) observed were diarrhea, nausea, and fatigue. These AEs were mostly grade 1. Grade 3 or higher AEs did occur and included neutropenia (13%), diarrhea (10%), and alanine aminotransferase/aspartate aminotransferase (10%).³

The UNITY-NHL study is an ongoing study enrolling patients with relapsed or refractory NHL who have an ECOG performance status of 0 to 2. The study excludes individuals who have had major surgery, chemotherapy, or immunotherapy, or show evidence of hepatitis B virus, hepatitis C virus or known HIV infection. Individuals with NHL who have undergone an autologous hematologic stem cell transplant within 6 months of the study or those who had prior therapy with a PI3K δinhibitor, were also excluded from the trial.

References

1. TG Therapeutics initiates rolling submission of New Drug Application (NDA) to US Food and Drug Administration for umbralisib as a treatment for patients with previously treated marginal zone lymphoma or follicular lymphoma [news release]. New York, New York: TG Therapeutics, Inc; January 16, 2020.https://bit.ly/2QYaNwg. Accessed January 16, 2020.
2. TG Therapeutics announces positive results from the UNITY-NHL phase 2b pivotal trial evaluating umbralisib monotherapy in patients with relapsed/refractory follicular lymphoma [news release]. New York, New York: TG Therapeutics, Inc; October 28, 2019.https://bit.ly/3agFUuU. Accessed January 16, 2020.
3. TG Therapeutics reports positive interim data from UNITY-NHL phase 2b trial evaluating umbralisib monotherapy in patients with marginal zone lymphoma at the 2019 AACR annual meeting [news release]. New York, New York: TG Therapeutics, Inc; April 1, 2019.https://bit.ly/3ajr9XU. Accessed Janaury 16, 2020.