The FDA granted Orphan Drug Designation to umbralisib, an investigational oral PI3K delta inhibitor as treatment for patients with follicular lymphoma, according to a press release from TG Therapeutics. This designation follows a New Drug Application for treatment of marginal zone lymphoma and follicular lymphoma, which was submitted to the FDA in October 2019, based on results from the phase IIb UNITY-NHL study.
The FDA granted an Orphan Drug designation to umbralisib (TGR-1202), an investigational oral PI3K delta inhibitor, as a treatment for patients with follicular lymphoma (FL), according to a press release from TG Therapeutics. This designation follows aNew Drug Application for umbralisib for the treatment of patients with marginal zone lymphoma (MZL) and FL, which was submitted to the FDA in October 2019, based on results from the phase IIb UNITY-NHL study (NCT02793583).1
In October 2019,TG Therapeutics announced that the study had met its primary end point of overall response rate(ORR), as determined by Independent Review Committee (IRC) assessment for all treated patients with FL. The target ORR for treatment with umbralisib was 40% to 50%, and all patients achieved an ORR in the target range.2
UNITY-NHL is evaluating the efficacy and safety of umbralisib in combination with ublituximab (TGTX-110) with or without bendamustine (Treanda) and of umbralisib alone in patients with previously treated non-Hodgkin lymphomas. All arms were experimental.
In the umbralisib plus ublituximab arm, patients received oral umbralisib and intravenous ublituximab daily. The umbralisib monotherapy arm follows the same dosing. In the triplet arm of umbralisib plus ublituximab plus bendamustine, chemotherapy is administered intravenously daily and umbralisib and ublituximab follow dosing from the other 2 arms.
The secondary end point of the study was progression-free survival, which considered from the date of randomization through the date of the first documented progression for up to 2 years.
Patients were eligible to enroll in the study given they had a diagnosis of non-Hodgkin lymphoma which could include diffuse large B-cell lymphoma, FL, mantle cell lymphoma, and MZL. Patients were required to be relapsed or refractory to prior standard therapy and could not be a candidate for high-dose therapy or autologous stem cell transplant (ASCT). Participants were also required to have an ECOG performance status of 0 to 2. Patients in the FL cohort had previously received at least 2 prior lines of therapy, including an anti-CD20 regimen and an alkylating agent.
The study excluded patients who had any major surgery, chemotherapy, or immunotherapy within 21 days of beginning treatment in the study. Patients were also ineligible for UNITY-NHL if they showed evidence of hepatitis B or C virus, infection from human immunodeficiency virus, has ASCT within 6 months of study entry, or prior therapy with a PI3K delta inhibitor.
“The receipt of orphan drug designation for umbralisib to treat patients with FL is another important milestone in the development and anticipated commercialization of umbralisib in MZL and FL,” said Michael S. Weiss, executive chairman and CEO of TG Therapeutics, in a statement. “We were pleased to announce last year that both the MZL and FL cohorts of the UNITY-NHL trial met their primary end points and have commenced our first rolling submission for these indications. We are excited by the progress so far and look forward to the completion of this submission targeted in the first half of this year.”