FDA Approves XPOVIO for Multiple Myeloma

Karyopharm Therapeutics announced the U.S. Food and Drug Administration (FDA) has approved XPOVIO® (selinexor), the Company's first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) medicine, in combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy. XPOVIO was previously approved under the FDA's Accelerated Approval Program for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody.

"Today's U.S. approval broadens the existing label for XPOVIO and allows Karyopharm to offer a new, highly active, treatment option to a significantly expanded patient population," said Sharon Shacham, PhD, MBA, Founder, President and Chief Scientific Officer of Karyopharm. "We believe the expanded reach of XPOVIO will address a critical need for patients with multiple myeloma given its novel mechanism of action, convenient oral administration and established rapid and sustained efficacy profile. The XPOVIO label expansion approval was supported by the pivotal Phase 3 BOSTON study, which was recently published in The Lancet. This approval was made possible by the patients, caregivers and physicians who participated in the clinical development of XPOVIO, as well as our global, dedicated Karyopharm team that has worked tirelessly to advance this innovative therapy to the greater multiple myeloma community."

"We plan to immediately launch XPOVIO in this earlier-line indication by leveraging our established commercial infrastructure and growing account base of academic institutions and community-based oncology practices," said Michael G. Kauffman, MD, PhD, Chief Executive Officer of Karyopharm. "In parallel to our commercial initiatives in the U.S., we continue to collaborate with the European Medicines Agency (EMA) on the Marketing Authorization Application (MAA) of XPOVIO with the goal of further growing the global reach of XPOVIO to more patients in need."

In addition to multiple myeloma, XPOVIO is also approved for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy.

The FDA approval of XPOVIO's expanded indication is supported by the results of the BOSTON study, a multi-center, Phase 3, randomized study (NCT03110562), which evaluated 402 adult patients with relapsed or refractory multiple myeloma who had received one to three prior lines of therapy. The study was designed to compare the efficacy, safety and certain health-related quality of life parameters of once-weekly XPOVIO (selinexor) in combination with once-weekly Velcade® (bortezomib) plus low-dose dexamethasone (SVd) versus twice-weekly Velcade® plus dexamethasone (Vd). The primary endpoint of the study was progression-free survival (PFS) and key secondary endpoints included overall response rate (ORR), rate of peripheral neuropathy, and others. Additionally, the BOSTON study allowed for patients on the Vd control arm to crossover to the SVd arm following objective (quantitative) progression of disease verified by an Independent Review Committee (IRC). The BOSTON study was conducted at over 150 clinical sites internationally.

Although the study had one of the highest proportions of patients with high-risk cytogenetics (~50%) as compared with other Velcade-based studies in previously treated multiple myeloma, the median PFS in the SVd arm was 13.9 months compared to 9.5 months in the Vd arm, representing a 4.4 month (47%) increase in median PFS (hazard ratio of 0.70; p=0.0075). The SVd arm also demonstrated a significantly greater ORR compared to the Vd arm (76.4% vs. 62.3%, p=0.0012). Importantly, SVd therapy compared to Vd therapy showed consistent PFS benefit and higher ORR across several important subgroups.