Karyopharm Therapeutics and the Menarini Group announced that the European Commission (EC) has granted Marketing Authorisation for NEXPOVIO (selinexor), a first-in-class, oral exportin 1 (XPO1) inhibitor, in combination with once-weekly bortezomib (Velcade) and low-dose dexamethasone (SVd) for the treatment of adults with multiple myeloma who have received at least one prior therapy.
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this approval for the extension of NEXPOVIO's indication in the European Union, the conditional marketing authorisation is now converted to a full approval.
The marketing authorisation, which marks the second indication for NEXPOVIO, is valid in all 27 member states of the EU as well as Iceland, Liechtenstein, Norway, and Northern Ireland.
Stemline Therapeutics B.V., a wholly owned subsidiary of the Menarini Group, will be responsible for all commercialization activities in Europe.
The approval follows a positive opinion granted in May 2022 by the CHMP based on results from the Phase 3 BOSTON study that demonstrated once-weekly SVd resulted in a statistically significant reduction in the risk of disease progression or death compared to standard twice-weekly bortezomib plus dexamethasone (Vd) regimen.
The results from the BOSTON study were published in The Lancet (Grosicki, et al.) in November 2020.
The Marketing Authorisation is based upon the Phase 3 BOSTON (Bortezomib, Selinexor and Dexamethasone) study, which was a multi-center, randomized study (NCT03110562) that 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 SVd versus twice-weekly Vd. The primary endpoint of the study was progression-free survival and key secondary endpoints included overall response rate, rate of peripheral neuropathy, and others.
NEXPOVIO, which is marketed as XPOVIO in the U.S., has been approved in the following oncology indications by the European Commission: in combination with dexamethasone for the treatment of multiple myeloma in adult patients who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, two immunomodulatory agents and an anti-CD38 monoclonal antibody, and who have demonstrated disease progression on the last therapy; and in combination with bortezomib and dexamethasone for the treatment of adults with multiple myeloma who have received at least one prior therapy.
The expanded NEXPOVIO indication now allows adult patients with multiple myeloma to be treated in earlier lines of therapy.
The indication for NEXPOVIO is valid in the EU Member States as well as Iceland, Liechtenstein, Norway, and Northern Ireland. NEXPOVIO is also approved in the UK under a Conditional Marketing Authorisation.
The extension of indication in combination with bortezomib and dexamethasone for the treatment of adults with multiple myeloma who have received at least one prior therapy is currently under review by Medicines and Healthcare Products Regulatory Agency.
NEXPOVIO is a first-in-class, oral exportin 1 (XPO1) inhibitor. NEXPOVIO functions by selectively binding to and inhibiting the nuclear export protein exportin 1 (XPO1, also called CRM1). NEXPOVIO blocks the nuclear export of tumor suppressor, growth regulatory and anti-inflammatory proteins, leading to accumulation of these proteins in the nucleus and enhancing their anti-cancer activity in the cell.
The forced nuclear retention of these proteins can counteract a multitude of the oncogenic pathways that, unchecked, allow cancer cells with severe DNA damage to continue to grow and divide in an unrestrained fashion.
The most frequent adverse reactions (≥30%) of selinexor in combination with dexamethasone were nausea, thrombocytopenia, fatigue, anaemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatraemia, neutropenia and leukopenia.
The most commonly reported serious adverse reactions (≥3%) were pneumonia, sepsis, thrombocytopenia, acute kidney injury, and anaemia.
Infections: Infection was the most common non-haematological toxicity. Upper respiratory tract infection and pneumonia were the most commonly reported infections with 25% of reported infections being serious and fatal infections occurring in 3% of treated adult patients.
Patients 75 years and older had a higher incidence of discontinuation due to an adverse reaction, higher incidence of serious adverse reactions, and higher incidence of fatal adverse reactions. ■