The Menarini Group, a prominent privately held international pharmaceutical company, and Karyopharm Therapeutics Inc., a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced that the European Commission (EC) has granted selinexor orphan Medicinal Product Designation. It is intended to be used to treat myelofibrosis (MF). In May 2022, the US Food and Medication Administration (FDA) designated Selinexor as an orphan drug for the treatment of MF.
Selinexor, a first-in-class XP01 inhibitor, is now being tested by Karyopharm in both monotherapy and combination with ruxolitinib in patients with MF who have had prior treatment experience. In accordance with an exclusive licence agreement signed in December 2021 between Karyopharm and Menarini, Menarini is in charge of marketing all NEXPOVIO indications, both present and future, in the European Economic Area, the United Kingdom, Switzerland, the CIS nations, Turkey, and Latin America. All marketing initiatives in Europe will be coordinated by Menarini’s fully owned subsidiary Stemline Therapeutics BV.
“We are very pleased to receive EC Orphan Drug Designation for selinexor, which will be used for the treatment of myelofibrosis”, “Building on our recent orphan drug designation by the FDA, this recognition continues to reinforce the significant unmet need for a drug with a new mechanism of action like selinexor to treat this devastating disease. Our clinical plans remain on track and We look forward to the continued development of selinexor in the treatment of MF.”
Reshma Rangwala , MD, PhD, Chief Medical Officer, Karyopharm
“Myelofibrosis is a complex and difficult-to-treat bone marrow disorder with limited therapeutic options, and we are committed to bringing new treatments to patients through our collaboration with Karyopharm. We are excited about the potential to bring selinexor to patients with myelofibrosis in Europe, pending positive study readings and regulatory approval”
Olivia del Puerto , MD LMS, Director of Oncology Medical Affairs – EMEA at Menarini.
About EMA Orphan Drug Designation
In the European Union (EU), orphan medical products are designated by the European Commission, which also approves the favourable recommendation made by the Committee of the European Medicines Agency (EMA) for orphan medicinal products. EMA Companies creating medicines for fatal or severely disabling conditions that affect fewer than five in 10,000 people in the European Union are eligible for orphan drug designation. A 10-year window of marketing exclusivity in the European Union following product clearance, lower payments, and access to a marketing authorisation centrally are available to medicines that meet the EMA’s orphan category requirements.
About MF
A uncommon kind of bone marrow malignancy called MF prevents the body from producing blood cells normally. It results in severe anaemia that can make a person feel weak and exhausted, substantial bone marrow scarring, and other health problems. Low platelet counts brought on by bone marrow scarring can potentially raise the risk of bleeding. Although it can happen at any age and affects both men and women equally, MF typically affects adults 50 years of age or older. The incidence is thought to be 1.5 instances per 100,000 individuals in the United States, according to the National Organization for Rare Diseases (NORD), while according to research, it is thought to be 0.5 cases per 100,000 people in northern European nations.
About NEXPOVIO (selinexor)
The European Commission has given the go-ahead for NEXPOVIO, which is sold as XPOVIO® in the US, to be used for the following oncology indications: I the treatment of multiple myeloma in adult patients who have undergone at least four prior therapies and whose disease is resistant to at least two proteasome inhibitors, two immunomodulatory drugs, and one anti-CD38 monoclonal antibody and who have shown disease progression on imaging tests. The member states of the European Union, as well as Iceland, Lichtenstein, Norway, and Northern Ireland, are covered by NEXPOVIO’s marketing authorisation.
First-in-class oral exportin 1 (XPO1) inhibitor NEXPOVIO. NEXPOVIO inhibits the nuclear export protein exportin 1 by specifically attaching to it (XPO1, also called CRM1). Tumor suppressor, growth regulator, and anti-inflammatory proteins are blocked from leaving the nucleus by NEXPOVIO, which causes an accumulation of these proteins in the nucleus and increases their anticancer activity in the cell. These proteins can be forced into nuclear retention, which can block a variety of oncogenic pathways that, if left unchecked, allow cancer cells with significant DNA damage to continue to grow and divide erratically.
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 calorie intake throughout treatment. For patients at risk of dehydration, intravenous hydration should be considered.
Concomitant prophylactic treatment with a 5-HT3 antagonist and/or other anti-nausea agents should be provided before and during treatment with NEXPOVIO.
Hematology:
Patients should have their complete blood count (CBC) evaluated at baseline and during treatment, and as clinically indicated. Monitor more frequently during the first two months of treatment.
Thrombocytopenia: Thrombocytopenic
events (thrombocytopenia and decreased platelet count) have been reported commonly in adult patients receiving selinexor, and may 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 use.
Patients with neutropenia should now be monitored for signs of infection and evaluated promptly.
Gastrointestinal Toxicity:
Nausea, vomiting, diarrhea, which can sometimes be severe and may require the use of antiemetic and antidiarrheal medications.
Weight loss and anorexia:
Body weight, nutritional status, and volume should be assessed in patients at baseline, during treatment, and as clinically indicated. It should be monitored more frequently during the first two months of treatment.
Confusional and Lightheadedness:
Patients should be advised to avoid situations in which lightheadedness or lightheadedness may be a problem and not to take other medications that may cause dizziness or lightheadedness without appropriate medical advice. Patients should be advised not to drive or operate heavy machinery until symptoms resolve.
Hyponatremia:
Patients should have sodium levels assessed at baseline, during treatment, and as clinically indicated. It should be monitored more frequently during the first two months of treatment.
Cataracts:
Selinexor may cause a new onset or exacerbation of cataracts. Ophthalmologic evaluation may be performed as clinically indicated. Cataracts should be treated according to medical guidelines, including surgery if warranted.
Tumor Lysis Syndrome (TLS):
TLS has been reported in patients receiving selinexor therapy. Patients at high risk for TLS should be closely monitored. Treat TLS immediately according to institutional guidelines.
Fertility, pregnancy and lactation
Women of childbearing potential/contraception in men and women: Women
of childbearing potential and adult men of reproductive potential should be advised to use effective contraceptive measures or abstain from sexual intercourse while receiving treatment with selinexor and for at least one week. week after the last dose of selinexor.
Pregnancy:
There are no data from the use of selinexor in pregnant women. The use of selinexor is not recommended during pregnancy or in fertile women not using contraception.
Lactation:
It is unknown whether selinexor or its metabolites are excreted in human milk. The risk of breast-feeding babies cannot be excluded. Breastfeeding should be discontinued during treatment with selinexor and for one week after the last dose.
Undesirable effects
Summary of the safety profile
The most common adverse reactions (≥30%) of selinexor in combination with dexamethasone were nausea, thrombocytopenia, fatigue, anemia, decreased appetite, weight loss, diarrhea, vomiting, hyponatremia, neutropenia, and leukopenia.
The most reported serious adverse reactions (≥3%) were pneumonia, sepsis, thrombocytopenia, acute kidney injury, and anemia.
Description of specific adverse reactions
Infections: infection was the most frequent non-haematological toxicity. Upper respiratory tract infection and pneumonia were the most common infections; in treated adult patients, 25% of reported infections were serious and 3% were fatal.
Elderly population
Patients 75 years of age and older had a higher incidence of treatment discontinuation due to an adverse reaction, a higher incidence of serious adverse reactions, and a higher incidence of fatal adverse reactions.
Reporting of suspected adverse reactions
It is important to report suspected adverse reactions after authorization of the drug. This allows continuous monitoring of the benefit/risk balance of the drug. Healthcare professionals are encouraged to report any suspected adverse reaction through the national reporting system indicated in Appendix V.
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