by C. H. Weaver M.D. updated 2/2019
The U.S. Food and Drug Administration (FDA) has granted Fast Track designation to an oral Selective Inhibitor of Nuclear Export (SINE) compound selinexor for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy.1 The Fast Track designation was based on the multi-center, single-arm Phase 2b STORM (Selinexor Treatment of Refractory Myeloma) study in approximately 122 patients with heavily pretreated, penta-refractory multiple myeloma.
Selinexor (KPT-330) is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound. Selinexor functions by binding with and inhibiting the nuclear export protein XPO1 leading to the accumulation of tumor suppressor proteins in the cell nucleus. This reinitiates and amplifies their tumor suppressor function and is believed to lead to the selective induction of apoptosis in cancer cells, while largely sparing normal cells.
Vogl and colleagues have now published the results of a larger clinical trial evaluating selinexor in combination with dexamethasone in patients with multiple myeloma that is refractory to current therapies.2 They evaluated selinexor and dexamethasone in patients who were refractory to lenalidomide, pomalidomide, bortezomib, carfilzomib, and anti-CD38 antibodies (daratumumab or isatuximab), having been previously treated with an average of 7 different treatment regimens.
Overall the therapy was well tolerated and 21% of these refractory patients responded to treatment with selinexor + dexamethasone. Selinexor maintains its “Fast Track” designation and continues to be evaluated in clinical trials.
The FDA’s Fast Track program facilitates the development of drugs intended to treat serious conditions and that have the potential to address unmet medical needs. A drug program with Fast Track status is afforded greater access to the FDA for the purpose of expediting the drug’s development, review and potential approval. In addition, the Fast Track program allows for eligibility for Accelerated Approval and Priority Review, if relevant criteria are met, as well as for Rolling Review, which means that a drug company can submit completed sections of its New Drug Application (NDA) for review by FDA, rather than waiting until every section of the NDA is completed before the entire application can be submitted for review.
Kumar SK, Lee JH, Lahuerta JJ, et al. Risk of progression and survival in multiple myeloma relapsing after therapy with IMiDS and bortezomib: a multicenter international myeloma working group study. Leukemia. 2012;26(1):149-157.