On October 31, 2022 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 European Commission (EC) has granted orphan medicinal product designation for selinexor for the treatment of myelofibrosis (MF) (Press release, Karyopharm, OCT 31, 2022, View Source [SID1234622618]). Selinexor was granted orphan drug designation in MF by the U. S. Food and Drug Administration (FDA) in May 2022. Karyopharm is currently evaluating selinexor, a first-in-class XP01 inhibitor, as monotherapy in patients with previously treated MF, and in combination with ruxolitinib in treatment-naïve patients. In December 2021, Karyopharm and Menarini entered into an exclusive licensing agreement whereby Menarini is responsible for commercializing all current and future indications of NEXPOVIO in the European Economic Area, United Kingdom and Switzerland, CIS countries, Turkey and Latin America. Stemline Therapeutics B.V., a wholly owned subsidiary of Menarini, is leading all commercialization activities in Europe.
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"We are very pleased to receive orphan medicinal product designation from the EC for selinexor for the treatment of myelofibrosis," said Reshma Rangwala, MD, PhD, Chief Medical Officer of Karyopharm. "Building on our recent orphan drug designation from the FDA, this recognition continues to reinforce the significant unmet need for a drug with a novel mechanism of action like selinexor for this devastating disease. Our clinical plans remain on track, and we look forward to the continued development of selinexor in MF."
"Myelofibrosis is a difficult-to-treat and complex disorder of the bone marrow with limited therapeutic options and we are committed to bringing novel treatments to patients through our collaboration with Karyopharm. We are excited about the potential to bring selinexor to myelofibrosis patients in Europe, pending positive study read-outs and regulatory approval," said Olivia del Puerto, MD LMS, Head of Medical Affairs Oncology – EMEA of Menarini.
About the EMA Orphan Designation
Orphan medicinal product designation in the European Union (EU) is granted by the European Commission which adopts the positive opinion issued by the European Medicines Agency (EMA) Committee for Orphan Medicinal Products. The EMA’s orphan designation is available to companies developing treatments for life-threatening or chronically debilitating conditions that affect fewer than five in 10,000 persons in the EU. Medicines that meet the EMA’s orphan designation criteria qualify for financial and regulatory incentives that include a 10-year period of marketing exclusivity in the EU after product approval, reduced fees and access to centralized marketing authorization.
About MF
MF is a rare type of bone marrow cancer that disrupts the body’s normal production of blood cells. It causes extensive scarring of the bone marrow, leading to severe anemia that can cause weakness and fatigue. Bone marrow scarring can also cause a low number of platelets, which increases the risk of bleeding. MF affects males and females in equal numbers and can occur at any age, although it usually affects individuals 50 years old or older. According to the National Organization of Rare Diseases (NORD), the incidence is estimated to be 1.5 cases per 100,000 people in the United States and in Northern European countries, based on studies, the incidence is estimated to be 0.5 cases per 100,000 people.1
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 adults 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 since October 1, 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.