FDA Delays Decision on Selinexor’s Approval for Heavily Treated Multiple Myeloma

The U.S. Food and Drug Administration is delaying its decision on a new drug application (NDA) seeking approval of selinexor in combination with dexamethasone for patients with multiple myeloma who failed at least three prior therapies.

This means that the FDA will decide whether to approve the oral treatment by July 6, three months later than the original April 6 date.

Karyopharm Therapeutics’ application, now under priority review, specifically addresses treatment of patients who have received at least three previous therapies and whose disease is refractory to at least one proteasome inhibitor, one immunomodulatory agent, and an antibody medication targeting the CD38 cell surface protein — found at high levels on multiple myeloma cells.

In a Feb. 26 meeting, the FDA’s Oncologic Drugs Advisory Committee (ODAC) recommended the agency wait for the findings of the Phase 3 BOSTON clinical trial (NCT03110562), which is assessing if adding selinexor to treatment with Velcade (bortezomib) and low-dose dexamethasone delays disease progression and extends the lives of patients with relapsed or refractory multiple myeloma.

The committee’s recommendation is considered but is non-binding regarding the FDA’s final decision on whether to approve selinexor.

After the meeting, and at the FDA’s request, Karyopharm submitted additional clinical information, which allowed the agency to extend the decision date by three months.

“We look forward to the continued collaboration with FDA in trying to meet the needs of patients with relapsed refractory multiple myeloma,” Sharon Shacham, PhD, Karyopharm’s founder, president, and chief scientific officer, said in a press release.

Selinexor is a selective inhibitor of nuclear export. It suppresses the function of a protein called XPO1, often found at higher levels in tumor cells, which exports tumor suppressor proteins out of the cell’s nucleus. Selinexor induces the accumulation of these tumor suppressors in the nucleus, leading to selective death of tumor cells.

The NDA was based on results from the Phase 2b STORM trial (NCT02336815), where selinexor was given in combination with low-dose dexamethasone to myeloma patients who did not respond to treatment with two immunomodulatory therapies, Revlimid (lenalidomide) and Pomalyst (pomalidomide), and two proteasome inhibitors, Velcade and Kyprolis (carfilzomib).

A subset of these patients, known as penta-refractory, also did not respond to an anti-CD38 monoclonal antibody, such as Darzalex (daratumumab) or isatuximab.

The most recent results of this trial showed a 25.4% response rate in penta-refractory patients, including two cases where the tumors completely disappeared. Responses lasted a median of 4.4 months.

Karyopharm has also submitted a marketing authorization application to the European Medicines Agency for conditional approval, which was granted accelerated assessment.

In the U.S., selinexor received orphan drug designation for multiple myeloma, as well as fast track status for people with multiple myeloma who failed three prior treatments.

The treatment is also being tested in the Phase 1/2 STOMP trial (NCT02343042), which is assessing adding selinexor to treatment regiments with Velcade, Pomalyst, Revlimid, Darzalex, and Kyprolis. Overall, 63% of the multiple myeloma patients responded to the combo approach, including 13% complete responses and 18% very good partial responses. The median time without disease worsening was 9.2 months.

Selinexor has also been granted fast track status for the treatment of patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not eligible for stem cell transplants. This decision was based on results from the Phase 2b SADAL study (NCT02227251), which showed partial or complete tumor disappearance in more than one-third of heavily treated DLBCL patients.