Karyopharm Reports Mixed Study Result, Raises $30 Million

Rare Daily Staff

Karyopharm Therapeutics reported mixed but promising results from a clinical trial in myelofibrosis, a rare blood cancer, and simultaneously secured $30 million in funding from a leading biotech investor to help carry its drug program forward.

In the phase 3 SENTRY study, researchers tested whether adding Karyopharm’s oral cancer drug Xpovio to the standard myelofibrosis medicine ruxolitinib could improve outcomes for people starting treatment for the disease.

Myelofibrosis affects the bone marrow’s ability to make healthy blood cells and often causes an enlarged spleen, severe fatigue, abdominal discomfort, and other debilitating symptoms. Currently approved treatments are limited to JAK inhibitors such as ruxolitinib, which can shrink the spleen and ease symptoms but do not work for everyone and may not fully control the disease over time.

Xpovio is an oral cancer medicine that contains the active ingredient selinexor, a targeted drug that blocks a transport protein called exportin 1 (XPO1) inside cells. By inhibiting XPO1, it keeps tumor‑suppressor and growth‑regulating proteins inside the cell nucleus, which can reactivate the cell’s own defenses and trigger cancer cell death while largely sparing normal cells.

The SENTRY trial enrolled 353 patients who had not previously received a JAK inhibitor and randomly assigned them to receive Xpovio plus ruxolitinib or ruxolitinib plus placebo. After 24 weeks, 50 percent of patients on the combination achieved at least a 35 percent reduction in spleen volume—a key measure known as SVR35—compared with 28 percent of those on ruxolitinib alone, a difference the company said was statistically significant. Spleen responses appeared quickly, with nearly half of patients on the combination reaching SVR35 by week 12, and were largely maintained through week 36.

However, the combination did not improve symptom burden beyond what ruxolitinib alone delivered. Both groups reported similar reductions in a standardized total symptom score at 24 weeks, so the trial missed its second main goal tied to symptom improvement. Although that endpoint fell short, Karyopharm and trial investigators emphasized two potentially important signals: overall survival and markers that may hint at underlying disease change.

In an early analysis of survival, patients on Xpovio plus ruxolitinib had an estimated 57 percent lower risk of death than those on ruxolitinib alone, though longer follow‑up is needed to confirm the benefit. Patients who achieved the deep spleen response tended to have better survival outcomes, reinforcing the idea that spleen shrinkage may be more than just a comfort measure. On a genetic level, 32 percent of patients on the combination achieved at least a 20 percent reduction in key driver mutations such as JAK2, MPL, and CALR, compared with 24 percent in the control arm, a possible sign of underlying disease impact that will need more study.

Clinicians involved in the trial framed the data as a step toward building on the benefits of JAK inhibitors rather than replacing them. John Mascarenhas of the Icahn School of Medicine at Mount Sinai said the combination “meaningfully improved spleen response” and showed “a promising signal in overall survival,” noting that reducing spleen volume remains one of the most important goals in myelofibrosis because of its association with longer life.

The side‑effect profile of the Xpovio–ruxolitinib combination was broadly in line with what doctors have already seen from each drug when used separately. The most common treatment‑emergent side effects in the combination arm included low platelets, anemia, nausea, constipation, and low neutrophil counts, with some of these events occurring more often than in the ruxolitinib‑only arm. Serious side effects were more frequent with the combination, and more patients stopped treatment because of side effects, though the rate of progression to acute leukemia was the same in both arms.

On the same day it released the SENTRY topline results, Karyopharm announced that RA Capital Management led a $30 million financing. Karyopharm agreed to sell just more than 1 million shares of common stock and about 3.4 million pre‑funded warrants, along with additional warrants tied to upcoming phase 3 results of Xpovio in endometrial cancer. If all of the accompanying warrants are exercised, Karyopharm could receive an additional $44 million on top of the initial $30 million.

The company said the new capital, together with existing cash and revenue, should allow it to fund operations into late third quarter 2026. Karyopharm plans to take the SENTRY data to the U.S. Food and Drug Administration to discuss whether the results are strong enough to support approval of Xpovio plus ruxolitinib for frontline myelofibrosis.