Karyopharm encouraged by interim study results of blood cancer treatment, eltanexor

Karyopharm announced interim data from the phase 2 study of eltanexor on Wednesday (May 3).

The data showed that eltanexor has promising single-agent efficacy with a generally manageable safety profile.

After the February 8, 2023, data cut-off date, 30 patients had been treated orally with 10mgs of eltanexor on days one to five of every week. This showed 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%.

It was generally well-tolerated and manageable with the most common adverse events being asthenia, diarrhea and nausea, the majority of which were grade 1-2. The most common grade 3 or above treatment-emergent AEs were neutropenia, thrombocytopenia and asthenia.

Chief medical officer of Karyopharm, Reshma Rangwala, said: “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.

 “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.”

The company’s research found that approximately 12,000 to 20,000 people in the United States are diagnosed with this type of blood cancer each year, with an estimated 87,000 new cases each year worldwide.

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.

The company said that 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.

It also noted that 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.