Karyopharm Therapeutics said today that its lead product candidate selinexor (KPT-330) is unlikely to meet its primary endpoint in a Phase II study assessing the cancer treatment in relapsed/refractory acute myeloid leukemia (AML).

Karyopharm said a planned interim analysis of the Phase II Selinexor in Older Patients with Relapsed/Refractory AML (SOPRA) trial led its independent Data Safety Monitoring Board and the company to conclude that selinexor will not show statistical significance for overall survival (OS), the study’s primary endpoint.

However, Karyopharm and the board agreed that patients who showed complete response following selinexor treatment could continue on the selinexor arm or the physician’s choice arm following discussion with their physicians, since those patients showed a greater OS benefit compared to physician’s choice. Among selinexor patients, 13% showed complete recovery with or without full hematologic recovery, versus 3% of physician’s-choice patients.

Some patients remained on selinexor for over a year, but that did not generate statistically superior OS compared to physician’s choice, Karyopharm said.

“While we are disappointed with the overall outcome, we are pleased that 60 mg of single-agent selinexor dosed twice per week was well-tolerated and carried no increased risk of sepsis or febrile neutropenia,” Karyopharm CEO Michael G. Kauffman, M.D., Ph.D., said in a statement. “At Karyopharm, our primary focus remains the advancement of selinexor in relapsed or refractory multiple myeloma, where we believe we have a clear path to regulatory approval.”

Karyopharm plans to continue clinical development of selinexor in AML through trials in multiple combination regimens, including with chemotherapy, citing what it termed encouraging data to date.

In SOPRA, 176 r/r AML patients were randomized 2:1 to receive either oral selinexor (60 mg twice per week) or one of four physician’s choice therapies: best supportive care (BSC), or BSC plus azacytidine (Vidaza®), decitabine (Dacogen®), or low-dose cytosine arabinoside (LD-AraC).

SOPRA’s primary endpoint was OS, with a target of a 75% improvement from 3 months in the physician’s-choice arm to 5.2 months with selinexor.

Selinexor is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE™) compound designed to bind with and inhibit the nuclear export protein XPO1 (also called CRM1), leading to the accumulation of tumor suppressor proteins in the cell nucleus. That activity is believed to lead to the selective induction of apoptosis in cancer cells, while largely sparing normal cells.

Selinexor is being assessed in several mid- and later-phase clinical trials, including in multiple myeloma with low-dose dexamethasone (STORM) and backbone therapies (STOMP), in diffuse large B-cell lymphoma (SADAL), and in liposarcoma (SEAL).

This year, Karyopharm plans to launch a Phase III combination study of selinexor with Takeda-marketed bortezomib (Velcade®) and low-dose dexamethasone (BOSTON) in multiple myeloma patients.

Investors sent shares down nearly 13% from yesterday’s close, to $12.05 as of 10:01 a.m.








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