Transition from Conditional to Full Marketing Authorization

On July 18, 2022, the European Commission converted the conditional marketing authorization for Nexpovio (selinexor) to a full marketing authorization. The initial conditional approval was granted on March 26, 2021, and the conditions were met through the submission of additional clinical data. The approved indication is for adult patients with multiple myeloma who have received at least one prior therapy, either in combination with bortezomib and dexamethasone, or in combination with dexamethasone in patients with multiple myeloma who have received at least four prior lines of therapy and are refractory to multiple agents. In the United States, the drug is marketed as Xpovio and received approval on July 3, 2019, for the indication of patients with multiple myeloma who have received at least four prior lines of therapy, and on December 18, 2020, for the indication of patients with multiple myeloma in combination with bortezomib and dexamethasone (SVd).

XPO1 Inhibition Mechanism and BOSTON Clinical Trial Data

Selinexor is an oral small molecule that selectively inhibits nuclear export protein XPO1, leading to the accumulation of tumor suppressor proteins in the nucleus and inducing cancer cell death. The pivotal Phase 3 BOSTON study, which served as the basis for full approval, compared selinexor, bortezomib, and dexamethasone (SVd) once weekly to bortezomib and dexamethasone (Vd) in patients with one to three prior lines of therapy. The median progression-free survival was 13.93 months versus 9.46 months, with a hazard ratio of 0.70 and a p-value of 0.0075, and the objective response rate was 76.4% versus 62.3%. This established the efficacy of adding an oral XPO1 inhibitor to a proteasome inhibitor-based regimen; however, management of toxicities such as thrombocytopenia, nausea, and fatigue is a prerequisite for expanding the use of the drug.

Menarini to Handle Commercialization in Europe

Karyopharm Therapeutics (KPTI) entered into an exclusive licensing agreement with Menarini Group in December 2021 for the commercialization of selinexor in the European Economic Area, the United Kingdom, Switzerland, and other regions. Karyopharm is eligible to receive an upfront payment of $75 million, as well as development, regulatory, and sales milestone payments of up to $225 million, plus tiered double-digit royalties on net sales. Menarini's wholly-owned subsidiary, Stemline Therapeutics B.V., is the marketing authorization holder and commercialization entity in Europe, so Karyopharm will secure a portion of product sales as royalties instead of incurring local sales organization costs. The total of $277.5 million represents the sum of the upfront payment and potential milestone payments, excluding royalties and equity investments.

Large Market, but High Competition

The global market for multiple myeloma is projected to reach $29.24 billion in 2025 and $31 billion in 2026. Nexpovio competes with Darzalex (daratumumab, CD38), Velcade (bortezomib, proteasome inhibitor), and Revlimid (lenalidomide, CRBN) in the standard-of-care regimens, and in relapsed patients, Carvykti (ciltacabtagene autoleucel, BCMA) and other bispecific antibodies are also expanding treatment options. Therefore, while full approval reduces regulatory uncertainty, market share will depend on reimbursement by individual European countries, management of toxicities, and placement in the treatment algorithm. Oral administration and the unique XPO1 mechanism of action are advantages, but the approval itself does not guarantee superiority over competing drugs.