The company has begun the process of submitting a new drug application to the U.S. Food and Drug Administration, which is expected to be completed in the second half of 2018.
In the U.S., selinexor, formerly known as KPT-330, has received orphan drug status for multiple myeloma and fast track status for multiple myeloma patients who failed three prior therapies. These designations are now expected to support and expedite the FDA’s regulatory review.
Karyopharm also expects to submit a marketing authorization application with a request for conditional approval to the European Medicines Agency in the beginning of 2019 for the same indication.
“We believe that selinexor has the potential to address the critical unmet need for patients with highly resistant, penta-refractory myeloma, where the disease is no longer responsive to standard approved therapies,” Sharon Shacham, PhD, founder, president, and chief scientific officer of Karyopharm, said in a press release.
Penta-refractory patients are those who received prior treatment with the two immunomodulatory therapies, Revlimid (lenalidomide) and Pomalyst (pomalidomide), the two proteasome inhibitors, Velcade (bortezomib) and Kyprolis (carfilzomib), and the anti-CD38 antibody, Darzalex (daratumumab).
These patients have also not responded to at least one proteasome inhibitor and one immunomodulatory therapy, Darzalex, and their most recent therapy.
STORM included nearly 150 patients with penta-refractory disease, who received 80 mg of selinexor along with low-dose dexamethasone at 20 mg, given twice a week in four-week cycles.
Top-line data announced in April showed that 25.4% of these patients responded to treatment, including two patients who achieved a complete response and 29 who had partial or very good partial responses.
“We are proud of the positive Phase 2b STORM study results underlying this application and we will work expeditiously to complete the submission this year,” Shacham said.
Selinexor is an oral selective inhibitor of nuclear export, or SINE, that targets the XPO1 protein. By inhibiting proteins from exiting the nucleus, this investigational treatment promotes the accumulation of tumor-suppressing proteins in the nucleus of cancer cells, inducing their death while sparing healthy cells.
If the medicine is approved, Karyopharm will need to confirm the benefits of selinexor in additional studies. To this end, the company is already conducting a Phase 3 trial (NCT03110562) to test if adding selinexor to a combination of Velcade and low-dose dexamethasone delays disease progression and extends patients’ lives.
The company is also testing selinexor with standard myeloma treatments in a Phase 1/2 trial (NCT02343042). Both studies are still recruiting participants.
Preliminary data from these trials revealed that selinexor improves the anti-cancer response in patients with refractory myeloma. These results were recently presented at the European Hematology Association annual meeting in Stockholm.