Karyopharm Therapeutics announced on Mar. 25 that its multiple myeloma drug Xpovio showed mixed results in a Phase 3 clinical trial for myelofibrosis, meeting only one of two primary endpoints. Following the announcement, the company's shares closed at $5.44, marking an 18.3% decrease from the previous closing price.
The company said it plans to discuss "the totality of the data" with the Food and Drug Administration to explore potential regulatory pathways for Xpovio in this new indication. However, analysts at Jefferies said, "We see low chance of conventional FDA approval w/ current dataset," according to a note sent to investors.
Xpovio is an oral nuclear export inhibitor that was approved in 2019 for use with dexamethasone in patients with relapsed or refractory multiple myeloma who have undergone at least four prior lines of therapy. Last year, Karyopharm reported $114.9 million in revenue from Xpovio and forecasts U.S. product revenue between $115 million and $130 million this year.
In the SENTRY study, more than 350 patients with myelofibrosis who had not previously received JAK inhibitors were treated either with a combination of Xpovio and ruxolitinib or placebo plus ruxolitinib. At week 24, half of those receiving the combination achieved at least a 35% reduction in spleen volume compared to 28% on ruxolitinib alone—a statistically significant difference that was sustained through week 36.
However, the regimen did not meet its other co-primary endpoint related to symptom improvement; patients on Karyopharm’s combination saw less improvement than those on ruxolitinib alone. A key opinion leader consulted by RBC Capital Markets said that ruxolitinib’s symptomatic benefits are so robust that it may be difficult for any drug to outperform it on this measure.
Karyopharm highlighted "promising" overall survival outcomes from its trial data, reporting a reduction in risk of death by 57% compared to controls when using the combination therapy. While some caution remains about whether these survival signals will persist over time, analysts noted that significant survival benefits could outweigh missing symptom score improvements if confirmed by further research.
The company intends to present its overall survival data to regulators as part of efforts toward expanding Xpovio's indications but has not provided a timeline for possible filings.
