Dive Brief:
- Karyopharm Therapeutics’ multiple myeloma drug Xpovio helped people with the blood disorder myelofibrosis on a key measure of health, but didn’t help reduce their symptoms when combined with the approved drug Jakafi in a Phase 3 trial, the company said Tuesday.
- The company said it plans to discuss the data with the Food and Drug Administration, aiming to seek an extended approval for Xpovio, its only marketed drug and source of revenue. Approval in myelofibrosis could be “transformative” for Karyopharm by tripling Xpovio revenue, which stood at $115 million in 2025, RBC Capital Markets analyst Brian Abrahams wrote in a note to clients.
- Following release of the data, Karyopharm announced it is raising $30 million from a private placement with healthcare investment firm RA Capital. Shares fell as much as 15% in Tuesday morning trading.
Dive Insight:
Myelofibrosis stems from bone marrow scarring that impedes the body’s ability to produce healthy blood cells. Symptoms include fatigue resulting from anemia, along with joint pain, frequent infections and a swollen spleen — the last a result of overwork from both filtering diseased blood cells and trying to make more healthy ones.
Spleen volume reduction has been used as a “surrogate endpoint” in clinical trials to demonstrate efficacy of myelofibrosis medicines, as it has been linked to better survival. Incyte’s Jakafi, the first targeted drug for myelofibrosis, won approval based on that measure.
In its fresh Phase 3 trial results, Karyopharm included a second endpoint called total symptom score.
The company recruited 353 people with myelofibrosis in the trial, randomizing two-thirds to receive Xpovio plus Jakafi and one-third to receive Jakafi and a placebo. At week 24, 50% of the enrollees who got the combination had a 35% reduction in their spleen volume, compared with 28% who took Jakafi and a placebo, a statistically significant difference.
But on total symptom score, there was no significant difference. The combination arm improved almost 10 points, while improvement in the Jakafi-plus-placebo group was roughly 1 point higher.
Karyopharm also noted a “signal” toward improved overall survival. About 5% of the people who got Xpovio and Jakafi died, compared with 10% in the control arm. However, the difference can’t be calculated as statistically significant. Karyopharm said it will continue to follow trial participants to determine if it can detect a such a difference.
“The stakes are high” in Karyopharm’s efforts to persuade the FDA and other regulators to approve Xpovio in myelofibrosis, Abrahams wrote. Despite having more than $100 million in sales from the drug, along with more than $30 million in revenue from international commercial partners, the company is still losing money — $196 million in 2025 alone. Those losses are accruing in spite of restructuring and layoffs conducted more than two years ago.
Still, Abrahams believes Karyopharm has a shot. “The data are clearly imperfect, but between spleen, survival, and hints of disease modification, we believe there is enough here to warrant regulatory discussions and an appetite among clinicians to have this in their treatment arsenal,” he wrote.
