Selinexor Gains FDA Fast Track Designation for Refractory Multiple Myeloma Patients

Selinexor, the lead oral therapy developed by Karyopharm Therapeutics, received Fast Track designation by the U.S. Food and Drug Administration (FDA), for the treatment of refractory multiple myeloma patients — those who have not responded to at least three prior lines of therapy.

Karyopharm’s hopes for Selinexor are based on the positive results obtained in clinical trials currently evaluating the therapy for multiple myeloma patients.

The Fast Track designation, given to therapies intended to treat serious health conditions, can accelerate the therapy’s development and approval by facilitating the FDA’s process.

“The designation of Fast Track for selinexor represents important recognition by the FDA of the potential of this anti-cancer agent to address the significant unmet need in the treatment of patients with penta-refractory myeloma that has continued to progress despite available therapies,” Sharon Shacham, PhD, MBA, founder, president and chief scientific officer of Karyopharm, said in a press release.

“We are fully committed to working closely with the FDA as we continue development of this potential new, orally-administered treatment for patients who currently have no other treatment options of proven benefit.” he added.

Selinexor is what’s known as a Selective Inhibitor of Nuclear Export, or SINE, compound. The compound induces the accumulation of tumour-suppressor proteins inside the cell nucleus, believed to selectively lead to the death of cancer cells, while sparing normal ones.

The Phase 2b STORM trial (NCT02336815) showed that patients with penta-refractory or quad-refractory multiple myeloma, who have been through three or more prior lines of therapy, responded positively to a combination of Selinexor with low-dose dexamethasone.

In the study, a patient is considered penta-refractory if he or she had received prior treatment with an alkylating agent, a glucocorticoid, two immunomodulatory drugs — Revlimid (lenalidomide) and Pomalyst (pomalidomide) , two proteasome inhibitors — Velcade (bortezomib) and Kyprolis (carfilzomib), and the monoclonal antibody Darzalex (daratumumab), and whose disease does not respond to at least one proteasome inhibitor, one immunomodulatory drug, Darzalex, and glucocorticoids and their most recent anti-myeloma therapy.

The trial, which is still recruiting participants, is testing a regimen of oral Selinexor (80 mg) combined with dexamethasone (20 mg), both given twice weekly in each four-week cycle. Its main goal is to determine the proportion of patients achieving a partial or a complete response to treatment.

Meanwhile, two other trials are underway to evaluate the efficacy and safety of Selinexor.

Positive preliminary results were reported for the Phase 1b/2 STOMP trial (NCT02343042) that is evaluating Selinexor plus low-dose dexamethasone combined with other approved therapies.

More recently, the Phase 3 BOSTON trial was launched to evaluate a combination of Selinexor, low-dose dexamethasone, and Velcade (NCT03110562) for relapse and refractory multiple myeloma.

In addition, a Phase 1 trial (NCT01607892) already completed, evaluated the efficacy of Selinexor alone or in combination with dexamethasone, for refractory multiple myeloma or  Waldenstrom’s macroglobulinemia, a type of lymphoma.

Overall, 25 percent of patients, largely myeloma patients, responded in some degree to treatment, with the combo therapy being the most efficient regimen.

In total, more than 2,300 patients have already received Selinexor, which is also being evaluated for other cancer types.