The US Food and Drug Administration (FDA) has granted orphan drug designation for IMO-8400, an antagonist of the endosomal Toll-like receptors (TLRs) 7, 8 and 9, for the treatment of Waldenström’s macroglobulinemia (WM).
The designation provides the drug’s maker, Idera Pharmaceuticals, with certain incentives, including eligibility for federal grants, research and development tax credits, and 7 years of marketing exclusivity if the product is approved.
Preclinical studies have shown that, in WM and other B‐cell lymphomas characterized by the MYD88 L265P oncogenic mutation, TLR signaling is overactivated. And this enables tumor cell survival and proliferation.
About 90% of WM patients are reported to harbor the MYD88 L265P mutation.
In research presented at the 2014 AACR Annual Meeting, investigators showed that IMO-8400 decreased the viability of mutated WM cells and diffuse large B-cell lymphoma (DLBCL) cells in vitro. The drug also decreased tumor growth and prolonged survival in mice with MYD88 L265P-positive DLBCL.
Now, Idera is conducting a phase 1/2 trial (NCT02092909) of IMO-8400 in patients with WM who have a history of relapse or failure to respond to one or more prior therapies. The protocol includes 3 dose-escalation cohorts of IMO-8400 administered subcutaneously.
The trial’s independent data review committee has completed its review of 4-week safety data from the second dose cohort (1.2 mg/kg/week) and has determined that Idera may open enrollment in the third dose cohort (2.4 mg/kg/week).
Final 24-week safety and clinical activity data are anticipated in the second half of 2015.
Aside from WM, Idera is pursuing clinical development of IMO-8400 in DLBCL patients harboring the MYD88 L265P mutation and in rare autoimmune diseases, including dermatomyositis.
