Karyopharm’s Expovio has stalled in the clinic and market after gaining approval for the treatment of multiple myeloma and achieving sales of $120 million in its third year on the market.
On Tuesday, the Massachusetts company provided results from a Phase 3 trial that it hopes will help its nuclear transportation modulator regain momentum. But investors didn’t share the company’s enthusiasm, and the stock price plummeted after the company’s initial public offering, which revealed other financial conditions for the company.
By testing Expovio (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 combination demonstrating a statistically significant greater than 35% improvement (SVR35) in spleen volume reduction compared to Jakafi and placebo.
Karyopharm said in a press release that the experimental combination caused spleen reactions in 50% of patients, compared to 28% in the control group.
However, the trial did not meet its co-primary endpoint due to poor patient-reported symptom scores after 24 weeks compared to baseline. As measured by Absolute Total System Score (Abb-TSS), patients who received Jakafi and placebo reported an improvement of 10.9 points, compared to patients who received the combo reported an improvement of 9.9 points.
Karyopharm CEO Richard Paulson said on a conference call Tuesday morning that the data is an “important milestone” for the company and “an encouraging step forward” for patients with MF.
“These results suggest the potential for improving key aspects of treatment efficacy in diseases where patients and physicians continue to need better options,” Paulson said, adding that the company plans to discuss the data and potential indication filings with the FDA.
Naturally, Karyopharm focused on the spleen volume aspect of this test, where this combination produces rapid and long-lasting results. After 12 weeks, 49% of patients in the combination group achieved SVR35, compared with 20% of patients in the control group. Durability of the combo was demonstrated with 47% of patients achieving baseline at week 36, compared to 23% of patients receiving Jakafi plus placebo.
Additionally, the company said trial results show a positive overall survival signal for this combination. Karyopharm added that post-hoc analyzes at weeks 12 and 24 suggested that SVR35 “may be predictive of overall survival.” The company will continue to monitor patients during the trial to assess overall survival.
“The significant proportion of patients who achieve that SVR early and sustainably, in addition to encouraging overall survival signals and a manageable safety and tolerability profile, are actually demonstrating that meaningful benefit, suggesting a real positive benefit,” Reshma Rangwala, MD, Karyopharm’s chief medical officer, said in a conference call. “We look forward to working with FDA on the completeness of that data.”
Separately on Tuesday, Karyopharm disclosed a new financing arrangement with RA Capital Management in which it plans to sell 1.03 million common shares at $6.79 per share for proceeds of $30 million. This may have played a role in the company’s stock move on Tuesday.
Karyopharm has struggled in recent years, with its stock price falling more than 95% over the past five years. The stock price fell about 17% after the two pieces of news were announced on Tuesday.
After winning FDA approval three times in 17 months for Expovio, the FDA rejected a bid to expand the drug’s use as a maintenance treatment for endometrial cancer. Annual sales for each of the past four years have been stagnant, hovering between $112 million and $120 million.
The company implemented a series of layoffs in 2023, reducing the number of employees by 20%. Last year it was reduced by another 20%. The company opened this year with 228 employees, down from 442 in early 2022.
