The U.S. Food and Drug Administration (FDA) has granted orphan drug status to eFT508, which treats diffuse large B-cell lymphoma (DLBCL) by inhibiting proteins associated with the disease.
The designation is offered only to therapies meant to treat rare diseases — those affecting fewer than 200,000 Americans. It qualifies eFT508’s maker, eFFECTOR, for treatment-development incentives, including tax credits for clinical testing.
“Diffuse large B-cell lymphoma is an aggressive disease for which patients badly need additional treatment options,” Steve Worland, PhD, president and chief executive officer of eFFECTOR, said in a news release. “We hope that eFT508, a selective translation regulator that blocks multiple oncogenic growth and proliferation pathways, as well as activates anti-tumor immunity, will prove effective in treating patients afflicted with this devastating disease.”
EFT508 is an oral, selective inhibitor of the MNK1 and MNK2 proteins. The two kinases play roles in multiple tumor-promoting signaling pathways, and regulate many disease-driving proteins, including checkpoint proteins. EFT508 works as a one-two punch against tumor cells: It targets and kills the cells directly. And it prevents tumor cells from tricking the immune system into failing to recognize them as foreign cells and eliminating them.
In preclinical models of hematological cancer, published in Blood, eFT508 treatment prevented the proliferation of multiple DLBCL cell lines. It also prevented the proliferation of human lymphoma cells in seven mice models.
In addition, the drug showed promise as a treatment foe blood cancers when combined with standard-of-care chemotherapy and targeted therapies, including Imbruvica (ibrutinib) and Venclexeta (venetoclax).
Based on the findings, eFFECTOR recently started a Phase 1 and 2 clinical trial (NCT02937675) to assess the safety, pharmacokinetics, pharmacodynamics, and anti-tumor activity of eFT508 in lymphoma patients. The open-label, sequential-group, dose-escalation, and cohort-expansion study will enroll up to 96 patients with previously treated lymphomas.
The study will be conducted in two parts. In Part 1, the escalation phase, multiple eFT508 doses will be evaluated to determine the maximum tolerated dose and a dose recommended for further evaluation. Patients will receive oral eFT508 daily for 21-day cycles.
In Part 2, the expansion phase of the trial, the recommended Phase 2 dose will be further tested for effectiveness.
EFFECTOR is already conducting an additional Phase 1/2 trial in patients with solid tumors (NCT02605083).