FDA grants priority review to selinexor for penta-refractory myeloma

The FDA granted priority review to selinexor for the treatment of patients with penta-refractory multiple myeloma, according to the agent’s manufacturer.

Selinexor (KPT-330, Karyopharm Therapeutics) is a first-in-class, oral selective inhibitor of nuclear export compound.

The drug binds with and inhibits the nuclear export protein XPO1, leading to the accumulation of tumor suppressor proteins in the cell nucleus. The goal of treatment is selective induction of apoptosis in cancer cells while sparing healthy cells.

“As a potential new therapy with a novel mechanism and compelling clinical profile, we believe oral selinexor, if approved, will provide a meaningful therapeutic option for patients battling highly resistant, penta-refractory myeloma,” Sharon Shacham, PhD, MBA, founder, president and chief scientific officer of Karyopharm, said in a company-issued press release. “The acceptance of this new drug application for review and grant of priority review mark significant milestones for the selinexor program, and further underscores the high level of unmet need in this patient population. We look forward to working with the FDA during the review process.”

The priority review designation applies to use of selinexor for patients who have received at least three prior lines of therapy, including regimens comprised of an alkylating agent; a glucocorticoid; the immunomodulatory drugs lenalidomide (Revlimid, Celgene) and pomalidomide (Pomalyst, Celgene); the proteasome inhibitors bortezomib (Velcade, Takeda/Millennium) and carfilzomib (Kyprolis, Amgen); and the anti-CD38 monoclonal antibody daratumumab (Darzalex, Janssen).

Eligible patients must have disease refractory to at least one proteasome inhibitor, at least one immunomodulatory drug, daratumumab, glucocorticoids and their most recent antimyeloma therapy.

The FDA previously granted fast track and orphan drug designations to selinexor for the same indication.

The FDA based these designations on topline results of the multicenter, single-arm, phase 2b STORM study, which included 122 patients with heavily pretreated penta-refractory myeloma.

Patients received 80 mg oral selinexor twice weekly plus 20 mg low-dose dexamethasone twice weekly. Overall response rate served as the primary endpoint. Secondary endpoints included duration of response and clinical benefit rate.

The FDA is expected to make a decision on approval of the agent by April 6, 2019.