Karyopharm slumps, then leaps on selinexor multiple myeloma data

Karyopharm Therapeutics’ stock took a bit of a roller-coaster ride Monday—it dipped 15% as investors waited for an update on the phase 2b trial of selinexor in patients with refractory multiple myeloma. It then jumped 26% after hours on positive topline data from the trial.

The multicenter, single-arm STORM study investigated selinexor, an oral, selective inhibitor of nuclear export, in 122 patients with penta-refractory multiple myeloma, meaning that they had been treated with, and stopped responding to, five different treatments for their disease.

Each patient was dosed with 80 mg of selinexor in combination with 20 mg of dexamethasone twice a week. The overall response rate was 25.4%, which includes two complete responses and 29 partial responses. The median duration of response was 4.4 months. The most common adverse events—nausea, vomiting, fatigue and reduced appetite—were “primarily low grade and manageable.”

“Despite numerous advances in myeloma treatment, currently available therapies are insufficient to address the increasing number of patients with highly resistant, penta-refractory myeloma, where the disease has ultimately become non-responsive to approved therapy,” said Paul Richardson, M.D., director of clinical research for the Jerome Lipper Multiple Myeloma Center at the Dana-Farber Cancer Institute.

“Selinexor’s targeted inhibition of nuclear export could potentially expand the armamentarium of treatment options significantly in this important population for which no other established treatment is readily available,” Richardson said.

Karyopharm aims to file an NDA for selinexor in multiple myeloma by the end of the year, with plans to submit a marketing authorization application to the EMA in 2019.

The Newton, Massachusetts-based biotech recently sold off a neurological drug, KPT-350, to Biogen in a deal potentially worth $217 million. It did so as “part of our broader strategy of partnering our non-oncology assets while we focus on our primary objective of executing the development of oral selinexor,” Karyopharm CEO Michael Kauffman, M.D., Ph.D., said at the time.

Analysts at Jefferies were impressed, saying in a note to clients: "Top-line penta-refractory data in multiple myeloma (MM) exceeded our expectations. The ORR at 25.4% (benchmark was ~20%) indicates a 95% CI of 18% to 34%, which, impressively, is superior to historical Darzalex in quad-refractory. We believe the new data affirm the importance of sel's differentiated MOA. Sel's convenience, accumulating combo data and confirmatory ph.III should fuel this story into launch and beyond -- the new data establish an inflection point."