The U.S. Food and Drug Administration (FDA) has granted fast track designation to MEI Pharma‘s investigational compound ME-401 for treating follicular lymphoma patients who received at least two prior therapies.
A therapy candidate is put on the FDA’s fast track if it can treat serious conditions and fill an unmet clinical need, either because no treatments are currently available or because the potential treatment offers significant benefits over approved therapies.
The designation is intended to speed the therapy’s development and possible approval by providing more frequent meetings with the FDA and discussions of development plans.
“We are pleased to report that we have received Fast Track designation for ME-401,” Daniel P. Gold, PhD, president and CEO of MEI Pharma, said in a press release. “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.”
ME-401 is a potent and selective inhibitor of PI3K delta, a protein involved in the signaling, development, and survival of immune B-cells, and often implicated in lymphomas mediated by this type of cell, including follicular lymphoma. By blocking this protein’s activity, ME-401 is designed to prevent cancer cells from replicating, which results in their death.
Other agents targeting PI3K delta also tend to kill normal B-cells, causing severe immune-related side effects that limit their clinical use. But ME-401 is designed for an intermittent dosing regimen that might reduce its toxicity while maintaining efficacy.
An ongoing Phase 1b trial (NCT02914938) exploring the safety and efficacy of ME-401 has demonstrated its safety and effectiveness across a series of B-cell lymphomas, including follicular lymphoma.
The trial — currently recruiting — plans to enrol 177 patients with relapsed or refractory follicular lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, and other B-cell lymphomas.
Patients receive a 60 mg dose of ME-401, alone or in combination with rituximab. While the standard ME-401 treatment regimen is to take this dose continuously every day, some patients were moved to an intermittent dosing schedule in which they took ME-401 only on the first week of each four-week cycle.
Results revealed a response to treatment in 78% of follicular lymphoma patients. These responses were durable — with more than half of patients still responding to treatment after a median follow-up of 9.2 months — and were significantly higher than the responses reported for similar approved therapies (42%–59%).
Response rates were similar when ME-401 was used as a single agent (79%) or in combination with rituximab (78%), suggesting that rituximab brought no benefit to patients.
As expected, severe immune-related side effects were lower among patients receiving ME-401 in an intermittent schedule (11%) than continuously (30%), but the treatment’s efficacy was not compromised with the intermittent schedule.
A global Phase 2 trial called TIDAL (NCT03768505) was later designed to confirm the risks and benefits of the intermittent schedule over the continuous one in relapsed or refractory follicular lymphoma.
The trial is ongoing and recruiting up to 166 participants across 93 clinical sites in North America, Europe, Asia, New Zealand, and Australia.
Participants must have received at least two prior lines of therapy, including a CD20 antibody and a chemotherapy regimen containing an alkylating agent or a purine analogue. They will be randomly assigned ME-401 in a continuous or an intermittent dosing regimen, but all will receive it continuously in the first two cycles.
The main goal is to compare response rates between the two groups. Secondary measures include duration of responses, proportion of complete responses, time to disease progression or death, and overall survival. Safety and how ME-401 behaves in the body — in terms of absorption, distribution, metabolism, and excretion — will also be assessed.
Pending positive results from TIDAL, MEI Pharma is planning to file a new drug application with the FDA asking for ME-401’s accelerated approval for relapsed or refractory follicular lymphoma.
