FDA Grants Fast Track Designation to PI3K Inhibitor ME-401 for Patients with FL

April 3, 2020

The FDA granted fast track designation to ME-401, an investigational selective oral inhibitor of PI3K delta, for the treatment of adult patients with relapsed or refractory follicular lymphoma.

The FDA granted fast track designation to ME-401, an investigational selective oral inhibitor of phosphatidylinositol 3-kinase (PI3K) delta, for the treatment of adult patients with relapsed or refractory follicular lymphoma who have received at least 2 prior systemic therapies, according to MEI Pharma, the agent’s developer.1

The company is currently conducting TIDAL (Trials of PI3K Delta in Hon-Hodgkin’s Lymphoma), which is a phase II trial assessing ME-401 in patients with relapsed or refractory lymphoma after failure of at least 2 prior systemic therapies, including chemotherapy and an anti-CD20 antibody. 

“This designation holds several important advantages to expedite the development and regulatory review of ME-401 as we work diligently to deliver it as a new potential treatment option for patients and their physicians,” Daniel P. Gold, PhD, president and chief executive officer of MEI Pharma, said in a press release. “We remain very encouraged by the maturing body of ME-401 clinical data, and we are excited to continue expanding the opportunity that ME-401 holds to provide a meaningful impact in the treatment of B-cell malignancies.”

Patients in the phase Ib study are administered 60 mg ME-401 once daily for two 28-day cycles, and then on an intermittent schedule of once daily dosing for the first 7 days of each subsequent 28-day cycle (i.e. the intermittent schedule or IS).2 In a previous cohort of monotherapy patient in the study, participants were treated with ME-401 administered continuously once daily or were switched to IS after cycle 2 was completed (i.e. the continuous schedule or CS).

In October 2019, MEI reported updated interim data from the phase Ib clinical trial. At the time of the update, over 95 patients were enrolled, of which 73 patients with relapsed or refractory follicular lymphoma or relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) patients were evaluable for efficacy. 

The data demonstrated that ME-401 achieved a high overall response rate of 81% among all evaluable follicular lymphoma and CLL/SLL patients. Moreover, the overall response rate was 78% and 89% in the 55 and 18 patients with follicular lymphoma or CLL/SLL, respectively. Additionally, high rates of response and durability were observed in patients administered ME-401 on the IS and CS regimens. 

ME-401 was found to be well-tolerated, and no grade 4 or grade 5 adverse events of special interest have been observed in the trial. Among notable drug related grade 3 adverse events, the most common was diarrhea or colitis at 5.0% (3 of 57) on IS dosing and 23% (9 of 39) on CS dosing. However, patients on the IS dosing regimen showed significantly improved overall tolerability.

Subject to the results and upon completion of the phase II clinical trial, the company is planning a submission to the FDA to support an accelerated approval marketing application.

In addition to the TIDAL study, MEI is also conducting a multi-arm, open-label, phase Ib dose escalation and expansion trial evaluating ME-401 as a monotherapy and in combination with other therapies such as rituximab (Rituxan) or agents such as zanubrutinib (Brukinsa) in patients with relapsed or refractory B-cell malignancies. 

References:

1. MEI Pharma Announces Fast Track Designation Granted by U.S. FDA for ME-401 For the Treatment of Adult Patients with Relapsed or Refractory Follicular Lymphoma [news release]. San Diego, California. Published March 31, 2020. investor.meipharma.com/2020-03-31-MEI-Pharma-Announces-Fast-Track-Designation-Granted-by-U-S-FDA-for-ME-401-For-the-Treatment-of-Adult-Patients-with-Relapsed-or-Refractory-Follicular-Lymphoma. Accessed April 3, 2020. 

2. MEI Pharma. ME-401. MEI Pharma website. Published 2019. meipharma.com/our-programs/me-401. Accessed April 3, 2020.