FDA Grants Fast Track Designation to Eltanexor Monotherapy in R/R Myelodysplastic Syndromes


Results from a phase 1/2 trial highlighted improved clinical outcomes for patients receiving eltanexor monotherapy for relapsed/refractory myelodysplastic syndrome.

The FDA has granted fast track designation to eltanexor (KPT 8602, ATG 016) monotherapy for patients with relapsed/refractory intermediate-, high-, or very high–riskmyelodysplastic syndrome (MDS), according to a press release from Karyopharm Therapeutics.1

A phase 1/2 trial (NCT02649790) is currently underway investigating eltanexor in patients with relapsed/refractory MDS.2 Eltanexor is an investigational selective inhibitors of nuclear export (SINE) compound that functions by binding with the nuclear export protein XPO1. This results in the accumulation of tumor suppressor proteins in the cell nucleus. This mechanism boosts tumor suppression function and could induce selective apoptosis in cancer cells and spare healthy cells.

Notably, preclinical models showed that eltanexor demonstrated a broad therapeutic window with minimal penetration to the blood-brain barrier. Due to this, investigators theorize that the it has potential as another SINE compound for the treatment of cancer. Moreover, animals that were treated with eltanexor showed less percentage of weight loss and improved food consumption compared with selinexor (Xpovio). In addition to this designation by the FDA, the European Commission granted orphan medicinal product to eltanexor for the treatment of MDS in the European Union. The FDA has previously granted eltanexor monotherapy orphan drug designation for MDS.3

“These recent designations from the FDA and European Commission reinforce eltanexor's potential to improve clinical outcomes for patients with relapsed/refractory MDS,” Richard Paulson, president, and chief executive officer of Karyopharm, said in the press release. “We are dedicated to advancing our ongoing clinical trials and remain committed to bringing eltanexor to these patients and their families as a new treatment option.”

Previous phase 1 results were presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting assessing eltanexor monotherapy in patients with hypomethylating agent–refractory MDS. A total of 20 patients enrolled on the trial, 15 of whom were evaluable for efficacy with a median age of 76 years. Patients had a median of 2 prior lines of treatment, and 93% had a high- or intermediate 2–risk disease per International Prognostic Scoring System criteria.

The trial evaluated those given eltanexor at a dose of 10 mg (n = 5) or 20 mg (n = 15) every day for 5 days per week of a 28-day cycle.

Overall, 35% of patients had a bone marrow complete response (CR) and 25% achieved stable disease. Of those evaluable for efficacy, 47% had a bone marrow CR and 33% had stable disease. In the 10 mg group, the bone marrow CR was 60% and 40% of patients achieved stable disease. In the 20 mg group, the bone marrow CR rate was 40% and 20% had stable disease.

Hematologic improvement and transfusion independence for at least 2 weeks was reported in 4 patients, with an additional 2 patients having trilineage hematologic improvement. The overall survival (OS) for the 7 patients who had a bone marrow CR was 11.86 months vs 8.67 months for those who did not have a bone marrow CR (HR, 0.27; P = .05). For patients with disease control, the median OS was 9.86 months vs 3.15 months for those who had progressive disease (HR, 0.38; P = .09). Of note, adverse effects were low-grade, dose-dependent, and reversible.


  1. Karyopharm granted regulatory designation for eltanexor for the treatment of myelodysplastic syndromes. News Release. Karyopharm Therapeutics. July 20, 2022. Accessed July 21, 2022. https://bit.ly/3zpvqId
  2. Lee S, Mohan S, Knupp J, et al. Updated overall survival of eltanexor for the treatment of patients with hypomethylating agent refractory myelodysplastic syndrome. J Clin Oncol. 2021;39(suppl 15):e19037. doi:10.1200/JCO.2021.39.15_suppl.e19037
  3. Karyopharm received orphan drug designation from the FDA for eltanexor for the treatment of myelodysplastic syndromes. News Release. January 24, 2022. Accessed July 21, 2022. https://bit.ly/3znInSG
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