Karyopharm Therapeutics has announced a favorable regulatory update regarding its Phase 3 SENTRY trial in myelofibrosis, along with its third-quarter 2024 financial results. The company is changing the co-primary endpoints of the SENTRY trial to absolute Total Symptom Score (TSS), a move supported by the FDA, leading investigators, and patient advocacy organizations. This adjustment is expected to increase the overall confidence in the trial's success. Top-line data from SENTRY is anticipated in the second half of 2025. The company's Q3 2024 total revenue reached $38.8 million, including $29.5 million from U.S. XPOVIO net product revenue. Karyopharm is narrowing its full-year 2024 total revenue guidance to $145-$155 million. The company's existing cash, cash equivalents, and investments are expected to fund planned operations into Q1 2026. Selinexor's potential in myelofibrosis and endometrial cancer represents approximately $1 billion in potential annual U.S. peak revenues each.
SENTRY Trial Endpoint Update
The co-primary endpoint in the Phase 3 SENTRY trial of selinexor in combination with ruxolitinib for JAK inhibitor-naive myelofibrosis patients will now be the absolute change in total symptom score (Abs-TSS) at Week 24. This replaces the previous endpoint of total symptom score improvement of ≥ 50% (TSS50). Spleen Volume Reduction ≥35% (SVR35) at Week 24 will remain a co-primary endpoint. The two co-primary endpoints will be tested sequentially, starting with SVR35 followed by Abs-TSS. The trial's sample size is being proactively increased to approximately 350 patients to further enhance statistical power.
According to Dr. John Mascarenhas, Principal Investigator of the Phase 3 SENTRY trial, the change to Abs-TSS as a co-primary endpoint signifies a new era in the evaluation of combination therapy and reflects a growing willingness by the FDA to incorporate more sensitive methods of evaluating symptoms in trials with active comparators.
Clinical Data and Market Opportunity
Phase 1 trial data of selinexor plus ruxolitinib showed promising results, with all evaluable patients achieving SVR35 at any time and 79% achieving SVR35 at week 24. The combination also demonstrated rapid, deep, and sustained improvements in average TSS, with an average reduction of 18.5 points compared to baseline. This compares favorably to the 11 to 14 point reduction observed with ruxolitinib alone in prior Phase 3 trials. Karyopharm estimates a $1 billion annual U.S. peak revenue opportunity in myelofibrosis, within a multi-billion dollar market.
Endometrial Cancer Program
Karyopharm is also advancing selinexor for endometrial cancer, particularly in patients with TP53 wild-type tumors. Exploratory subgroup data from the SIENDO trial presented at ASCO revealed a median PFS of 28.4 months for selinexor versus 5.2 months for placebo in this population (HR=0.44). In the MMR proficient subgroup, selinexor demonstrated a median PFS benefit of 39.5 months compared to 4.9 months for placebo (HR=0.36). The pivotal XPORT-EC-042 Phase 3 trial in TP53 wild-type endometrial cancer is ongoing, with top-line data expected in early 2026. The company estimates a $1 billion annual U.S. peak revenue opportunity in endometrial cancer.
Third Quarter 2024 Financial Results
Key financial highlights from Karyopharm's third quarter 2024 results include:
- Total revenue: $38.8 million, compared to $36.0 million in Q3 2023
- U.S. XPOVIO net product revenue: $29.5 million, compared to $30.2 million in Q3 2023
- R&D expenses: $36.1 million, compared to $35.6 million in Q3 2023
- SG&A expenses: $27.6 million, compared to $30.8 million in Q3 2023
- Net loss: $32.1 million, or $0.26 loss per share, compared to $34.5 million, or $0.30 loss per share in Q3 2023
- Cash, cash equivalents, and investments: $133.9 million as of September 30, 2024
Karyopharm is narrowing its full-year 2024 guidance, with total revenue expected to be in the range of $145 to $155 million and U.S. XPOVIO net product revenue in the range of $110 to $115 million. R&D and SG&A expenses are projected to be between $255 and $265 million. The company expects its current financial resources to fund planned operations into the first quarter of 2026.
