FDA Grants Fast Track Designation to Eltanexor for R/R Myelodysplastic Syndrome

Following positive phase 1 study results for eltanexor monotherapy in patients with relapsed or refractory intermediate, high-, or very high-risk myelodysplastic syndrome, the FDA has granted the drug fast track status.

The FDA has granted fast track designation to the development of single-agent eltanexor (KPT-8602) for the treatment of patients with relapsed or refractory intermediate, high-, or very high-risk myelodysplastic syndrome (MDS), according to a press release issued by Karopharm Therapeutics.1

Eltanexor is a novel oral, selective inhibitor of nuclear export (SINE) compound that was previously granted orphan drug designation by the FDA. Outside of the United States, the agent has been deemed an orphan medicinal product for the treatment of MDS by the European Commission (EC).

"These recent designations from the FDA and EC reinforce eltanexor's potential to improve clinical outcomes for patients with relapsed/refractory MDS, “said Richard Paulson, president and chief executive officer of Karyopharm, in a 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."

Eltanexor is currently being evaluated in a phase 1/2 study of patients with relapsed/refractory cancer indication, which includes a cohort of patients with MDS (NCT02649790).

The first-in-human, multi-center, open-label clinical study of eltanexor is being conducted in 2 parts. During the first portion, patients are administered eltanexor at escalating doses. The second portion is the dose-expansion stage.2

In part 1, 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. Part 2 will investigate the coprimary end points of ORR, MTD, and progression-free survival (PFS). The part-2 secondary end points include OS, 6-month OS, PFS, DCR, DOR, and transfusion dependence or independence.2

Previously, data were reported from a subgroup of 20 patients with hypomethylating agent (HMA)-refractory MDS treated during phase 1 of the study.3 The results showed that eltanexor monotherapy has activity in high-risk HMA-refractory MDS. Moreover, patients who achieved marrow complete response (mCR) had prolonged median overall survival (mOS) compared with patients who did not achieve an mCR or those with progressive disease (HR, 0.27; P =.05 and HR, 0.23; P =.0, respectively).

Of the 20 patients with HMA-refractory MDS enrolled in the study, 15 were evaluable for efficacy. The median age of the cohort was 76 years (range, 62-89 years). The patients had a median of 2 prior treatment regimen (range, 1-4 regimens). Importantly, 93% of the cohort were high- or intermediate-risk per the International Prognostic Scoring System (IPSS).

A mCR was observed in 35% of the overall population, and 25% had stable disease (SD), which showed DCR of 60%. Of the efficacy evaluable patients, the mCR was 47% with SD in 33%. Results also showed that the lower dose of eltanexor (10 mg) achieved a higher mCR (60%) compared with the 20 mg cohort (40%).

Hematologic improvement was observed in 4 patients in the study. The patients became transfusion independent for at least 8 weeks.

For the phase 2 portion of the study, patients are being recruited. To be eligible for inclusion in the study, patients must be 18 years of age or older with adequate hepatic and renal functions. For the MDS cohort in particular, patients must 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. It is also required 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, and an ECOG performance status of < 2.


1. Karyopharm granted regulatory designations for eltanexor for the treatment of myelodysplastic syndromes. News release. Karyopharm Therapeutics. July 20, 2022. Accessed July 21, 2022. https://bit.ly/3IVqBJI

2. Study of the safety, tolerability and efficacy of KPT-8602 in participants with relapsed/refractory cancer indications. ClinicalTrials.gov. Updated July 1, 2022. Accessed July 21, 2022. https://clinicaltrials.gov/ct2/show/NCT02649790

3. 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. 2022;39(15). doi:10.1200/JCO.2021.39.15_suppl.e19037