On May 3, 2023 Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported interim data from the Phase 2 portion of the open-label Phase 1/2 study of single-agent eltanexor in patients with higher R/R myelodysplastic neoplasms (Press release, Karyopharm, MAY 3, 2023, View Source [SID1234630928]). The data, featured in a poster presentation at the 17th International Congress on Myelodysplastic Syndromes, showed that eltanexor has promising single-agent efficacy with a generally manageable safety profile.

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As of the February 8, 2023 data cut-off date, 30 patients had been treated with 10mg eltanexor, oral, on Days 1-5 of each week. Eltanexor demonstrated a 27% overall response rate (ORR) in the intent-to-treat (ITT) population and a 31% ORR in the efficacy evaluable population. Median overall survival (mOS) was 8.7 months in both populations. Transfusion independence rate for red blood cells and/or platelets was 29%.

Eltanexor was generally well-tolerated and manageable. The most common adverse events (AEs) were asthenia (47%), diarrhea (43%), and nausea (33%), the majority of which were Grade 1-2. The most common Grade ≥3 treatment-emergent AEs were neutropenia (30%), thrombocytopenia (26.7%), and asthenia (16.7%).

"Existing first-line treatments for higher risk MDS are not typically curative; approximately half of these patients do not respond. Upon progression, median overall survival for these higher risk, relapsed or refractory MDS patients is approximately four to six months. There is a critical need for novel and more effective treatment options for this patient population," said Reshma Rangwala, MD, PhD, Chief Medical Officer of Karyopharm. "We are encouraged by the improved overall survival observed to date with eltanexor in this higher risk patient population. These preliminary results are promising and reinforce the potential of XPO1 inhibition to provide meaningful clinical benefit to patients with relapsed/refractory myelodysplastic neoplasms."

Approximately 12,000 to 20,000 people in the United States are diagnosed with MDS each year, with an estimated 87,000 new cases each year worldwide3. HMAs are the current standard of care for newly diagnosed, higher risk MDS patients, who are not candidates for transplant. However, only about 50% of patients respond, with these responses typically lasting less than two years.4 The prognosis of higher risk relapsed/refractory disease is poor, with a median overall survival of four to six months.1,2 There are a limited number of novel agents currently in clinical development for relapsed refractory MDS.

About Eltanexor

Eltanexor (KPT-8602) is an investigational novel SINE compound that functions by binding with, and inhibiting, the nuclear export protein, XPO1, leading to the accumulation of tumor suppressor proteins in the cell nucleus. This reinitiates and amplifies their tumor suppressor function and is believed to lead to the selective induction of apoptosis in cancer cells, while largely sparing normal cells.

In preclinical models, eltanexor has a broad therapeutic window with minimal penetration of the blood brain barrier and, therefore, has the potential to serve as another SINE compound for cancer indications. Following oral administration, animals treated with eltanexor show lower percentage of body weight loss and improved food consumption than animals similarly treated with selinexor. This allows more frequent dosing of eltanexor, enabling a longer period of exposure than is possible with selinexor.

Eltanexor is an investigational medicine and has not been approved by the United States Food and Drug Administration or any other regulatory agency.