After gaining approval to treat multiple myeloma and generating sales of $120 million in its third full year on the market, Karyopharm’s Xpovio has stagnated in the clinic and in the market.
On Tuesday, the Massachusetts company provided results from a phase 3 trial that it hopes can help the nuclear transport modulator regain some of its momentum. But investors aren’t sharing in the company’s enthusiasm, with shares falling sharply after the readout and a separate financial development at the company.
Testing Xpovio (selinexor) in combination with Incyte and Novartis’ blockbuster Jakafi (ruxolitinib) in patients with first-line myelofibrosis (MF), the study met one of its two primary endpoints, with the combo demonstrating a statistically significant improvement in spleen volume reduction of 35% or more (SVR35) compared to Jakafi and placebo.
The experimental combo produced spleen responses in 50% of patients, compared to a 28% figure for the control arm, Karyopharm said in a press release.
The trial did not achieve its co-primary endpoint, however, it came up short on patient-reported symptom scores after 24 weeks compared to baseline. As measured by the Absolute Total System Score (Abb-TSS), patients on the combo reported a 9.9-point improvement, compared to a 10.9 improvement for those on Jakafi and placebo.
On a Tuesday morning conference call, Karyopharm CEO Richard Paulson called the data an “important milestone” for the company and “an encouraging step forward” for patients who have MF.
“These results suggest the potential to improve on key dimensions of treatment benefit in a disease where patients and physicians continue to need better options,” Paulson said, adding that the company plans to meet with the FDA to discuss the data and a potential submission for approval in the indication.
Naturally, Karyopharm focused on the spleen volume aspect of the trial, in which the combo produced rapid and sustained results. After 12 weeks, 49% of patients on the combo achieved SVR35 compared to 20% in the control arm. The durability of the combo was demonstrated at week 36 by 47% of patients achieving the standard compared to 23% of those on Jakafi and placebo.
Additionally, the company said the trial results indicated a positive overall survival signal for the combo. Karyopharm added that post-hoc analyses at weeks 12 and 24 suggest SVR35 “may predict overall survival.” The company will continue to monitor patients in the trial to evaluate overall survival.
“The early, the sustained, the substantial proportion of patients that achieved that SVR really demonstrates that meaningful benefit, layered on top of the promising overall survival signal and a manageable safety and tolerability profile really suggest a positive benefit,” Reshma Rangwala, M.D., Ph.D., Karyopharm’s chief medical officer, said during the call. “We look forward to engaging with the FDA on the totality of that data.”
Separately on Tuesday, Karyopharm revealed a new financing arrangement with RA Capital Management, under which it will generate $30 million in proceeds from the sale of 1.03 million shares of its common stock for $6.79 each. This likely played some role in the company’s share movement Tuesday.
Karyopharm has struggled in recent years, with its share price declining more than 95% over the last 5 years. After the twin news releases Tuesday, shares were down some 17%.
After gaining three FDA nods in a span of 17 months for Xpovio, the FDA rejected an expansion bid for the drug to be used as a maintenance therapy in endometrial cancer. In each of the last four years, annual sales have been stagnant, toggling between $112 million and $120 million.
In 2023, the company executed a round of layoffs, reducing its headcount by 20%. Last year came another 20% reduction. It opened this year with 228 employees, down from 442 at the start of 2022.