On February 21, 2023 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, and the Menarini Group ("Menarini"), a privately-held, leading international pharmaceutical company, reported that the United Kingdom’s (UK) Medicines and Healthcare Products Regulatory Agency (MHRA) has granted full Marketing Authorization 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 adult patients with multiple myeloma who have received at least one prior therapy (Press release, Karyopharm, FEB 21, 2023, View Source [SID1234627443]). With this approval extending NEXPOVIO’s indication in Great Britain, the conditional marketing authorization is now converted to full approval. Stemline Therapeutics B.V., a wholly owned subsidiary of the Menarini Group, will be responsible for all commercialization activities in the UK.
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The approval is based on findings 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.
"Receiving full marketing authorization from the MHRA marks another significant milestone for NEXPOVIO," said Richard Paulson, President and Chief Executive Officer of Karyopharm. "We are thrilled to expand the positive impact of NEXPOVIO to people living with multiple myeloma across Great Britain and continue working to further broaden access to selinexor across the globe."
"We are pleased by the MHRA’s decision to expand the indication for NEXPOVIO in Great Britain, bringing this important medicine to more people living with myeloma who may benefit," said Elcin Barker Ergun, Chief Executive Officer of Menarini. "We look forward to delivering NEXPOVIO to patients and physicians in Great Britain as quickly as possible."
About the BOSTON study
The Marketing Authorization is based on 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. To learn more about this study, please refer to the Karyopharm press release announcing the publication of the BOSTON study results in The Lancet, issued on November 12, 2020.
About NEXPOVIO (selinexor)
NEXPOVIO, which is marketed as XPOVIO in the U.S., has been approved in the following oncology indications by the European Commission: (i) 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 (ii) in combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy. The marketing authorization of NEXPOVIO is valid in the EU Member States as well as Iceland, Liechtenstein, Norway, and Northern Ireland. NEXPOVIO has been commercially available in Germany and Austria since Q4 2022.
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.
Please see NEXPOVIO Summary of Product Characteristics and European Public Assessment Report at View Source
Please refer to local prescribing information where XPOVIO/NEXPOVIO is approved for full information.
IMPORTANT SAFETY INFORMATION
Contraindications: Hypersensitivity to selinexor.
Special warnings and precautions for use:
Recommended concomitant treatments
Patients should be advised to maintain adequate fluid and caloric intake throughout treatment. Intravenous hydration should be considered for patients at risk of dehydration.
Prophylactic concomitant treatment with a 5-HT3 antagonist and/or other anti-nausea agents should be provided prior to and during treatment with NEXPOVIO.
Haematology:
Patients should have their complete blood counts (CBC) assessed at baseline, during treatment, and as clinically indicated. Monitor more frequently during the first two months of treatment.
Thrombocytopenia:
Thrombocytopenic events (thrombocytopenia and platelet count decreased) were frequently reported in adult patients receiving selinexor, which can be severe (Grade 3/4). Patients should be monitored for signs and symptoms of bleeding and evaluated promptly.
Neutropenia:
Severe neutropenia (Grade 3/4) has been reported with selinexor.
Patients with neutropenia should be monitored for signs of infection and evaluated promptly.
Gastrointestinal toxicity:
Nausea, vomiting, diarrhoea, which sometimes can be severe and may require the use of anti-emetic and anti-diarrhoeal medicinal products.
Weight loss and anorexia:
Patients should have their body weight, nutritional status and volume checked at baseline, during treatment, and as clinically indicated. Monitoring should be more frequent during the first two months of treatment.
Confusional state and dizziness:
Patients should be instructed to avoid situations where dizziness or confusional state may be a problem and to not take other medicinal products that may cause dizziness or confusional state without adequate medical advice. Patients should be advised not to drive or operate heavy machinery until symptoms resolve.
Hyponatraemia:
Patients should have their sodium levels checked at baseline, during treatment, and as clinically indicated. Monitoring should be more frequent during the first two months of treatment.
Cataract:
Selinexor can cause new onset or exacerbation of cataract. Ophthalmologic evaluation may be performed as clinically indicated. Cataract should be treated as per medical guidelines, including surgery if warranted.
Tumour lysis syndrome (TLS):
TLS has been reported in patients receiving therapy with selinexor. Patients at a high risk for TLS should be monitored closely. Treat TLS promptly in accordance with institutional guidelines.
Fertility, pregnancy and lactation
Women of childbearing potential/contraception in males and females:
Women of childbearing potential and male adult patients of reproductive potential should be advised to use effective contraceptive measures or abstain from sexual intercourse while being treated with selinexor and for at least 1 week following the last dose of selinexor.
Pregnancy:
There are no data from the use of selinexor in pregnant women. Selinexor is not recommended during pregnancy and in women of childbearing potential not using contraception.
Breast-feeding:
It is unknown whether selinexor or its metabolites are excreted in human milk. A risk to breast-fed children cannot be excluded. Breast-feeding should be discontinued during treatment with selinexor and for 1 week after the last dose.
Undesirable effects
Summary of the safety profile
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.
Description of selected adverse reactions
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.
Elderly population
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.
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions after Authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.