'Compelling results from Karyopharm study using combination of drugs to treat myelofibrosis

By Liza Laws

- Last updated on GMT

© Getty Images
© Getty Images

Related tags Clinical trial Pharmaceutical industry myelofibrosis AACR nausea

Symptom improvements have been hailed as ‘very compelling’ after results from a phase 1 study into a combination of drugs to treat myelofibrosis prove positive.

Pharma company, Karyopharm Therapeutics, works on producing cancer therapies and announced the updated results on Tuesday (April 18). The study is evaluating the safety and efficacy of once-weekly selinexor in combination with ruxolitinib in patients with treatment-naïve myelofibrosis.

The disease means bone and marrow fibrosis and relates to the development of fibrous or scar tissue. The scar tissue builds up in the bone marrow and blood cells can’t develop properly. It can affect people of any age but usually targets middle-aged and older people, the average age at diagnosis is 65.

The data, featured in a poster presentation at the American Association for Cancer Research (AACR) annual meeting held this year (2023), show that rapid, deep, and sustained spleen responses and robust symptom improvement were achieved at both weeks 12 and 24, in patients treated with selinexor 60mg in combination with ruxolitinib.

The data cut-off date was February 24, by which time 24 patients had been assigned to either a 40mg or 60mg once weekly dose of selinexor with the ruxolitinib. They all began treatment more than 24 weeks beforehand.

Both the 40mg and 60mg dose levels of selinexor were generally well tolerated and manageable, allowing most patients to remain on therapy, up to 68 weeks, as of the data cut-off date.

Common side-effects regardless of grade that were experienced with both drugs included nasusea and anemia which were slightly higher in the 60mg dose and fatigue which was slightly lower in the higher dose. 

Adverse events excperienced with both doses of selinexor in combination with ruxolitinib were anemia, thrombocytopenia and neutropenia. 

There were two treatment-related discontinuations, one due to thrombocytopenia and one due to peripheral neuropathy. Three-quarters of the nausea were grade one, were mostly transient and didn't lead to treatment-related discontinuations. Nausea rates and grades were reduced for patients who received prophylactic antiemetics. Meaningful weight gain was noted during the last week despite the nausea. 

Reshma Rangwala, chief medical officer of Karyopharm. “We are enthusiastic about the impressive spleen volume reductions and robust symptom improvement that have been observed with the 60mg dose of selinexor and ruxolitinib combination at week 24, which represent very meaningful improvements relative to the current standard of care of ruxolitinib alone.”

He explained the data suggested that the combination of selinexor and ruxolitinib has the potential to be a transformative therapy for first line myelofibrosis patients. He said the company was ‘very encouraged’ by the preliminary data showing rapid normalization in platelets and stability of hemoglobin levels, as potential evidence of disease modification for these patients.

He added: “We look forward to building upon these findings as we plan the initiation of a pivotal phase 3 study in front-line myelofibrosis later this quarter.”

Haris Ali is a doctor at the City of Hope Comprehensive Cancer Center.

He said: “There remains significant unmet need in the treatment of myelofibrosis, with less than half of patients achieving an SVR35 with the current standard of care therapy.

“The spleen responses and symptom improvements seen across all patients with the 60mg selinexor dose is very compelling. These data suggest this tolerable and unique combination of XPO1 and JAK inhibition has the potential to significantly improve these key efficacy measures for first line myelofibrosis patients.”

Both the efficacy and safety data support the 60mg dose of selinexor as the recommended dose in combination with ruxolitinib. A double-blind, randomized, phase 3 trial of selinexor 60mg in combination with ruxolitinib versus placebo in combination with ruxolitinib in JAKi treatment-naïve patients with myelofibrosis is expected to initiate in the first half of this year.

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