Karyopharm Therapeutics recently announced that the U.S. Food and Drug Administration (FDA) has accepted its supplemental New Drug Application (sNDA) for Xpovio (selinexor), seeking approval for a new indication for the treatment of patients with multiple myeloma (MM) who have received at least one prior therapy. The FDA expects to make a decision by the end of the first quarter of 2021.
This sNDA is based on positive topline results from the Phase III BOSTON study. This study evaluated the efficacy and safety of once-weekly Xpovio in combination with once-weekly Velcade (bortezomib) and low-dose dexamethasone (SVd) and twice-weekly Velcade in combination with low-dose dexamethasone (Vd) in patients with relapsed or refractory MM who have received 1-3 prior lines of therapy. Vd is a standard treatment for MM.
The results showed that the study met its primary endpoint: compared with the vitamin D (Vd) treatment group, the SVd treatment group had a 47% increase in progression-free survival (PFS) of 4.47 months (median PFS: 13.93 months vs. 9.46 months), and a significant 30% reduction in the risk of disease progression or death (HR=0.70, p=0.0066). Previously, the SVd treatment group had also shown a significant improvement in overall response rate (ORR) compared to the Vd treatment group. No new safety signals were observed in the SVd treatment group in this study, and there was no imbalance in mortality between the two groups.
Dr. Sharon Shacham, Founder, President, and Chief Scientific Officer of Karyopharm, stated, “This sNDA acceptance brings us closer to making Xpovio available to more MM patients. If approved, we believe Xpovio will be an important new, oral, once-weekly treatment option, in combination with once-weekly Velcade (bortezomib), for the treatment of MM patients who have received at least one prior therapy.”
The active pharmaceutical ingredient in Xpovio is selinexor, a first-in-class, oral, selective nuclear export inhibitor (SINE) compound that works by binding to and inhibiting the nuclear export protein XPO1 (also known as CRM1). This leads to the accumulation of tumor suppressor proteins in the cell nucleus, which reactivates and amplifies their tumor-suppressive function, resulting in selective apoptosis of cancer cells without significantly affecting normal cells.
In the United States, Xpovio has been approved by the FDA for two oncology indications for the treatment of pentadal refractory multiple myeloma (MM) and relapsed or refractory diffuse large B-cell lymphoma (DLBCL): (1) in combination with dexamethasone for patients with relapsed or refractory multiple myeloma (RRMM) who have received at least four prior lines of therapy and are refractory to at least two proteasome inhibitors (PIs), at least two immunosuppressants (IMiDs), and one anti-CD38 monoclonal antibody; and (2) for the treatment of adult patients with relapsed or refractory DLBCL, including DLCBL caused by follicular lymphoma (FL), who have received at least two prior lines of systemic therapy.
Xpovio is the first and only FDA-approved nuclear export inhibitor (SINE), and the first approved drug targeting a novel myeloma target (XPO1) since 2015. Furthermore, Xpovio is currently the only approved single-agent oral therapy for the treatment of relapsed or refractory DLBCL.
If this sNDA is approved, Xpovio will provide an important addition to the treatment modality for patients with relapsed or refractory MM. Currently, Karyopharm is evaluating the potential of selinexor in multiple mid-to-late stage clinical trials for a range of hematologic malignancies and solid tumors, including multiple myeloma (MM), diffuse large B-cell lymphoma (DLBCL), liposarcoma (SEAL study), endometrial cancer, and recurrent glioblastoma.
