FDA Grants Orphan Drug Designation to Eltanexor for Myelodysplastic Syndrome

For the treatment of patients with myelodysplastic syndrome, the FDA has granted an orphan drug designation to eltanexor.

A novel oral, selective inhibitor of nuclear export (SINE) compound, eltanexor (KPT-8602), has been granted orphan drug designation by the FDA for the treatment of patients with myelodysplastic syndrome (MDS), according to a press release from Karyopharm Therapeutics, Inc.1

Preclinical research around elanexor showed that it may increase expression of type 1 interferon on interferon stimulating genes like ISG15 and ISG54. The agent targeted XPO1, which is overexpressed in many cancer types and correlates with poor prognosis in patients.2

Treatment with elanexor in patients with MDS, as well as other hematologic malignancies and solid tumors, is underway in a phase 1/2 trial (KCP-8602-801; NCT02649790). The open-label study is evaluating the safety, tolerability, and efficacy of the agent in 119 patients. In part 1 of the study, the coprimary end points are determining the maximum-tolerated dose (MTD) and recommended phase 2 dose, as well as overall response rate (ORR), duration of response (DOR), overall survival (OS), clinical benefit rate (CBR), duration of CBR, disease control rate (DCR), and duration of disease control. As a secondary end point, part 1 of the study will look at pharmacokinetics.

In part 2 of the study, the coprimary end points include ORR, MTD, and progression-free survival (PFS), while secondary end points are OS, 6-month OS, PFS, DCR, DOR, and transfusion dependence or independence.

The study allows patients who are 18 years of age or older with adequate hepatic and renal functions. For the MDS cohort specifically, patients are required to have relapsed/refractory high-risk disease, and documented diagnosis of MDS with 5% to 19% myeloblasts in the bone marrow according to the 2016 World Health Organization classification. The study also requires that patients have a documented marrow histopathology by recent bone marrow biopsy, intermediate, high- or very-high-risk MDS by IPSS-R, HMA (primary)-refractory MDS, an ECOG performance status of < 2.

Patients cannot have imminent risk of AML transformation, newly diagnosed, intermediate/high-risk MDS, or prior therapy for MDS. The study also excludes patients who have IPSS-R very low or low-risk MDS, Participants who demonstrate doubling of their bone marrow blast percentage within 4 weeks prior to Screening and have absolute blast percentage of > 15% at the time of screening, those who previously underwent transplant, those previously treated with either chemotherapy, azacitidine, decitabine or other demethylating agents; or lenalidomide (Revlimid), thalidomide (Thalomid), or pomalidomide (Pomalyst). Patients with active graft-versus-host disease of grade 2 or higher, or who are taking concurrent use of corticosteroids equivalent of prednisone at a dose > 0.5 mg/kg are ineligible for the study.

With an orphan drug designation for the treatment of patients with MDS, the developer of eltanexor will be eligible for certain development incentives from the FDA. Currently, the agent has no approved indication in the United States.

"We are pleased to receive the FDA's orphan drug designation for eltanexor in MDS and believe it reinforces eltanexor's potential to improve clinical outcomes for patients with HMA-refractory MDS," said Richard Paulson, president and chief executive officer of Karyopharm, in a press release.1 "We are focused on advancing our ongoing clinical trials and remain steadfast in our commitment to bringing this new treatment option to patients and their families."


1. Karyopharm receives orphan drug designation from FDA for eltanexor for the treatment of myelodysplastic syndromes. News release. January 24, 2022. Accessed January 25, 2022. https://bit.ly/3ICnkOc

2. Study of the safety, tolerability and efficacy of KPT-8602 in participants with relapsed/refractory cancer indications. Clinicaltrials.gov. Accessed January 25, 2022. https://bit.ly/3KEYjUd