Eltanexor Gets FDA Fast Track Status and Orphan Medicinal Product Designation in Europe for MDS

Pipeline Report: July 2022

Eltanexor has been granted a fast track designation from the FDA and an orphan medicinal product designation from the European Commission for use as a potential therapeutic option in patients with myelodysplastic syndromes.

myelodysplastic syndrome

Eltanexor (KPT-8602) has been granted a fast track designation from the FDA for use as a single agent in the treatment of patients with relapsed or refractory, intermediate-, high-, or very high–risk myelodysplastic syndromes (MDS).1 The European Commission (EC) also decided to designate the agent as an orphan medicinal product for use in this disease in the European Union.

The investigational SINE compound binds with and inhibits the nuclear export protein XP01; this leads to tumor suppression protein accumulation in the cell nucleus. This process serves to reinitiate and strengthen the tumor suppressor function and has been hypothesized to lead to selective induction of apoptosis in cancer cells, largely sparing normal cells.

The efficacy, safety, and tolerability of the agent is currently under investigation in patients with relapsed or refractory cancers, including MDS, as part of a phase 1/2 trial (KCP-8602-801; NCT02649790).2

“These recent designations from the FDA and EC reinforce eltanexor’s potential to improve clinical outcomes for patients with relapsed/refractory MDS,” Richard Paulson, president and chief executive officer of Karyopharm Therapeutics, Inc., stated 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 has been shown to result in a lower percentage of loss of body weight and improved food consumption vs selinexor (Xpovio) in animal models. Based on these preclinical data, investigators have hypothesized that more frequent dosing is possible with the agent than with selinexor; this allows for a longer period of drug exposure.

Additional findings from an investigator-sponsored, phase 1 trial demonstrated that single-agent eltanexor produced an overall response rate (ORR) of 53% in patients with MDS that was refractory to hypomethylating agents (HMAs). In these patients, the agent also resulted in an overall survival (OS) of 9.9 months; this favorably compares with the 4- to 6-month survival that has historically been observed in this population.

Initial data from the cohort of patients with HMA-refractory MDS included in the phase 1 portion of the ongoing, open-label, phase 1/2 trial have been reported. To participate, patients were required to have high-risk or intermediate-2 disease per the International Prognostic Scoring System (IPSS), and myeloblasts ranging from 5% to 19%.2 They also needed to be at least 18 years of age and have adequate hepatic and renal function.

If patients underwent a major surgical procedure within 4 weeks prior to day 1 of cycle 1, had impaired cardiac function or significant cardiac disease, known symptomatic brain metastases, select prior malignancies, or uncontrolled active severe systemic infection requiring parenteral antibiotics, antivirals, or antifungals within 1 week of treatment, they were excluded.

Data from a subgroup analysis presented during the 2021 ASCO Annual Meeting focused on 15 evaluable patients.3 The drug was evaluated at 10 mg in 5 patients and 20 mg in 15 patients; the agent was administered daily for the duration of 5 days each week of a 28-day cycle.

In the 15 evaluable patients, the median age was 76 years (range, 62-89); the majority of patients (93%) had IPSS high- or intermediate-2–risk disease, and the median number of prior treatments received was 2 (range, 1-4).

In the 20 total patients, 35% experienced a marrow complete response (mCR) and 25% achieved stable disease. Moreover, the disease control rate was 60% in these patients. In the 15 patients evaluable for efficacy, the mCR was 47% with the agent, and 33% achieved stable disease. All patients who received eltanexor at 10 mg derived clinical benefit; 60% had a mCR and 40% had stable disease. Among those who received the agent at 20 mg, the mCR was 40% and 30% had stable disease with treatment.3

Additional findings showed that a total of 4 patients experienced hematologic improvement (HI) and became transfusion independent for at least 8 weeks; this included 2 patients with trilineage HI.3

The median OS was found to be significantly longer in the 7 patients who experienced a mCR with the agent compared with those who did not, at 11.86 months and 8.67 months, respectively (HR, 0.27; P = .05). Those who achieved a mCR with eltanexor also experienced a longer OS than those who experienced progressive disease (n = 3); the median OS in the latter population was 3.15 months (HR, 0.23; P = .04).3

The 12 patients who achieved disease control with eltanexor were found to also experience a numerically longer OS compared with those who experienced disease progression; the median OS in these groups was 9.86 months vs 3.15 months, respectively (HR, 0.38; P = .09). Moreover, those with HI had a median OS of 10.58 months with the agent.3

Previously, in January 2022, the FDA granted an orphan drug designation to eltanexor for use as a potential therapeutic option in patients with MDS.4


  1. Karyopharm granted regulatory designations for eltanexor for the treatment of myelodysplastic syndromes. News release. Karyopharm Therapeutics, Inc. July 20, 2022. Accessed July 21, 2022. https://bit.ly/3omoHrY
  2. Study of the safety, tolerability and efficacy of KPT-8602 in participants with relapsed/refractory cancer indications. ClinicalTrials.gov. Updated December 30, 2021. 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. 2021;39(suppl 15):e19037. doi:10.1200/JCO.2021.39.15_suppl.e19037
  4. Karyopharm receives orphan drug designation from FDA for eltanexor for the treatment of myelodysplastic syndromes. News release. Karyopharm Therapeutics, Inc.; January 24, 2022. Accessed July 21, 2022. https://bit.ly/35lX8sH
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