Benzinga | Oct 21, 2021 12:11PM EDT

Karyopharm Announces Dosing Of First Patient In A Phase 2 Study Investigating Oral Eltanexor In HMA Refractory Myelodysplastic Syndrome

Karyopharm Therapeutics Inc. (NASDAQ:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced dosing of the first patient in the Phase 2 expansion of an ongoing open-label Phase 1/2 study investigating eltanexor, a novel oral, Selective Inhibitor of Nuclear Export (SINE) compound, as a single-agent or in combination with approved and investigational agents in patients with several types of hematologic and solid tumor cancers (KCP-8602-801; NCT02649790). The Phase 2 expansion is designed to evaluate eltanexor monotherapy in patients with hypomethylating agents (HMA) refractory, intermediate or high-risk myelodysplastic syndrome (MDS). The primary endpoint for this Phase 2 expansion is overall response rate (ORR) with the secondary endpoints of determining progression-free and overall survival.

Initiation of the Phase 2 expansion follows encouraging results from the Phase 1 portion of the study where single-agent eltanexor showed activity in patients with high-risk, relapsed MDS that was refractory to HMAs. In that study (Sangmin, et al. EHA 2021), eltanexor demonstrated a 53% ORR and a median overall survival of 9.9 months, comparing favorably to historical controls. At the recommended Phase 2 dose of 10 mg, eltanexor monotherapy was well tolerated with low incidence and grade of gastrointestinal events. Exacerbation of cytopenias occurred in 20-40% of patients. Based on these promising signals, the study has been expanded to include an additional 83 patients with the first patient recently dosed.

"MDS is a group of diseases characterized by ineffective production of the components of the blood due to poor bone marrow function, leading to a high risk of transformation into acute leukemia. HMAs are the current standard of care for patients with newly diagnosed, higher-risk MDS, however only 40-60% patients respond, with these responses typically lasting less than two years. As such, prognosis in HMA refractory disease is poor, with a median overall survival of four to six months. With no agents currently approved for primary HMA refractory MDS, the need for novel, efficacious agents is critical. Based on the promising signal observed in the prior Phase 1 study, we are pleased to initiate dosing in the Phase 2 expansion and look forward to updating you on the progress of this important study in the future," said Sharon Shacham, PhD, MBA, Co-Founder and Chief Scientific Officer of Karyopharm.