- Karyopharm and Menarini Group Announce European Commission Orphan Drug Designation for Selinexor in the Treatment of Myelofibrosis
NEWTON, Mass. and FLORENCE, Italy, Nov. 1, 2022 /PRNewswire/ -- Karyopharm Therapeutics Inc. (NASDAQ: KPTI), a commercial-stage pharmaceutical company pioneering new cancer therapies, and Menarini Group ("Menarini" ), a leading international private pharmaceutical company, today announced that the European Commission (EC) has granted orphan drug designation to selinexor for the treatment of myelofibrosis (MF). Selinexor was granted orphan drug designation for MF by the US Food and Drug Administration (FDA) in May 2022. Karyopharm is currently evaluating selinexor, a first-in-class XP01 inhibitor, as a monotherapy in patients with MF previously treated, and in combination with ruxolitinib in untreated patients. In December 2021, Karyopharm and Menarini signed an exclusive license agreement whereby Menarini is responsible for marketing all current and future indications of NEXPOVIO® in the European Economic Area, United Kingdom and Switzerland, CIS countries, Turkey and America. Latin. Stemline Therapeutics B.V., a wholly-owned subsidiary of Menarini, directs all marketing activities in Europe.
"We are very pleased to receive EC Orphan Drug Designation for selinexor for the treatment of myelofibrosis," said Reshma Rangwala, MD, PhD, Karyopharm's Chief Medical Officer. "This recognition, in addition to our recent orphan drug designation by the FDA, 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 further developing selinexor for MF."
"Myelofibrosis is a complex and difficult-to-treat bone marrow disorder with limited therapeutic options, and we are committed to bringing novel treatments to patients through our collaboration with Karyopharm. We are excited to make selinexor available to patients with myelofibrosis in Europe, pending positive study results and regulatory approval," said Olivia del Puerto, MD LMS, Director of Oncology Medical Affairs – EMEA at Menarini.
About EMA Orphan Drug Designation Orphan drug designation in the European Union (EU) is granted by the European Commission, which adopts the positive opinion issued by the Committee for Orphan Drugs of the European Medicines Agency (EMA). EMA Orphan Drug Designation is available to companies developing treatments for life-threatening or chronically debilitating diseases that affect fewer than five in 10,000 people in the EU. Medicines that meet the EMA's orphan drug designation criteria benefit from financial and regulatory incentives including a 10-year period of market exclusivity in the EU after product approval, reduced fees and access to a marketing authorization centralized.
About MFMF 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 men and women equally and can appear at any age, although it usually affects people 50 years of age or older. According to the National Organization for Rare Diseases (NORD), the incidence is estimated at 1.5 cases per 100,000 people in the United States and in the countries of northern Europe, according to studies, the incidence is estimated at 0.5 cases per 100,000 people.1
About NEXPOVIO® (selinexor)NEXPOVIO®, which is marketed as XPOVIO® in the United States, 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 one 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 for NEXPOVIO is valid in the EU Member States, as well as in Iceland, Liechtenstein, Norway and Northern Ireland. NEXPOVIO is commercially available in Germany from October 1, 2022.
NEXPOVIO is the first oral exportin 1 (XPO1) inhibitor. NEXPOVIO works 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 regulator, and anti-inflammatory proteins, causing these proteins to accumulate in the nucleus and enhancing their anticancer activity in the cell. Forced nuclear retention of these proteins can counteract a multitude of oncogenic pathways that, unchecked, allow cancer cells with severe DNA damage to continue to grow and divide uncontrollably.
See the NEXPOVIO® Summary of Product Characteristics and European Public Assessment Report at link
Please consult the local prescribing information where XPOVIO/NEXPOVIO is approved for complete 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 calorie intake throughout treatment. Intravenous hydration should be considered for patients at risk of dehydration.
Concomitant prophylactic treatment with a 5-HT3 antagonist and/or other anti-nausea agents should be administered prior to and during treatment with NEXPOVIO®.
Patients should have their complete blood count (CBC) assessed at baseline, during treatment, and as clinically indicated. Monitor more frequently during the first two months of treatment.
Thrombocytopenic events (thrombocytopenia and decreased platelet count), which may be serious (Grade 3/4), have been reported commonly in adult patients receiving selinexor. Patients should be monitored for signs and symptoms of bleeding and promptly evaluated.
Severe neutropenia (grade 3/4) has been reported with selinexor.
Neutropenic patients should be monitored for signs of infection and promptly evaluated.
Nausea, vomiting, diarrhoea, which can sometimes be severe and may require the use of antiemetic and antidiarrheal medications.
Weight loss and anorexia:
Patients should monitor their body weight, nutritional status, and volume at baseline, during treatment, and when clinically indicated. Control should be more frequent during the first two months of treatment.
Confusional state and dizziness:
Patients should be instructed to avoid situations in which dizziness or confusion may be a problem and not to take other medications that may cause dizziness or confusion without appropriate medical advice. Patients should be advised not to drive or operate heavy machinery until symptoms resolve.
Patients should monitor their sodium levels at baseline, during treatment, and when clinically indicated. Control should be more frequent during the first two months of treatment.
Selinexor may cause the onset or exacerbation of cataracts. An ophthalmologic evaluation may be performed as clinically indicated. Cataract should be treated according to medical guidelines, including surgery if warranted.
Tumor lysis syndrome (TLS):
Cases of TLS have been reported in patients receiving selinexor treatment. Patients at high risk of developing it should be closely monitored. Promptly treat TLS according to institutional guidelines.
Fertility, pregnancy and lactation
Women of childbearing potential/contraception in men and women:
Women of childbearing potential and adult male patients of reproductive potential should be advised to use effective contraceptive measures or to refrain from sexual intercourse while taking selinexor and for at least 1 week after the last dose of selinexor. selinexor.
There are no data from the use of selinexor in pregnant women. The use of selinexor is not recommended during pregnancy and in women of childbearing potential not using contraception.
It is unknown whether selinexor or its metabolites are excreted in human milk. A risk to breastfed infants cannot be excluded. Breast-feeding should be discontinued during treatment with selinexor and for 1 week after the last dose.
Security Profile Summary
The most common adverse reactions (≥30%) of selinexor in combination with dexamethasone were nausea, thrombocytopenia, fatigue, anemia, decreased appetite, weight decreased, diarrhea, vomiting, hyponatremia, neutropenia, and leukopenia.
The most frequently reported serious adverse reactions (≥3%) were pneumonia, sepsis, thrombocytopenia, acute kidney injury, and anemia.
Description of selected adverse reactions
Infections: Infection was the most frequent non-hematological 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 of age and older had a higher incidence of 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
Reporting of suspected adverse reactions after drug authorization is important. It allows continuous monitoring of the benefit/risk balance of the drug. Healthcare professionals are asked to report any suspected adverse reaction via the national reporting system listed in Appendix V.
About Karyopharm Therapeutics Karyopharm Therapeutics Inc. (Nasdaq: KPTI) is a commercial-stage pharmaceutical company pioneering new cancer therapies. Since its founding, Karyopharm has been the industry leader in oral selective nuclear export inhibitor (SINE) technology, which was developed to address a fundamental mechanism of oncogenesis: nuclear export dysregulation. Karyopharm's lead SINE compound and first oral exportin 1 (XPO1) inhibitor, XPOVIO® (selinexor), is approved in the United States and marketed by the company in three oncology indications and has received regulatory approvals across multiple indications in a growing number from territories and countries outside the United States, including Europe and the United Kingdom (as NEXPOVIO®), China, Singapore, Canada, Israel, South Korea and Australia. Karyopharm has a portfolio of projects focused on multiple unmet high-need oncology indications, including multiple myeloma, endometrial cancer, myelodysplastic syndromes and myelofibrosis. For more information about our people, our science, and our product portfolio, visit www.karyopharm.com, and follow us on Twitter at @Karyopharm and LinkedIn.
About Menarini GroupThe Menarini Group The Menarini Group is a leading international pharmaceutical and diagnostics company with more than $4 billion in sales and more than 17,000 employees. Menarini focuses on therapeutic areas with high unmet needs with products for cardiology, oncology, pulmonology, gastroenterology, infectious diseases, diabetology, inflammation and analgesia. With 18 production plants and 9 research and development centers, Menarini products are available in 140 countries around the world. For more information, visit www.menarini.com and LinkedIn.
Forward Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding the ability of selinexor to treat patients with multiple myeloma and expectations regarding the future development Clinical and potential regulatory presentations of selinexor. Such statements are subject to numerous important factors, risks and uncertainties, many of which are beyond Karyopharm's control, which could cause actual events or results to differ materially from Karyopharm's current expectations. For example, there can be no guarantee that Karyopharm will successfully market XPOVIO®; or that any of Karyopharm's drug candidates, including selinexor and eltanexor, will successfully complete the necessary clinical development phases or that development of any of Karyopharm's drug candidates will continue. In addition, there can be no assurance that any positive developments in the development or commercialization of Karyopharm's portfolio of drug candidates will result in a share price appreciation. Management's expectations, and therefore any forward-looking statements contained in this press release, could also be affected by risks and uncertainties related to a number of other factors, including the following: the risk that the COVID pandemic -19 may disrupt Karyopharm's business more seriously than it currently anticipates, including negative impact on sales of XPOVIO, disruption or delay of research and development efforts, impact on ability to obtain a supply sufficient for the development and commercialization of selinexor or other product candidates, the delay of ongoing or planned clinical trials, the impediment of the execution of business plans, anticipated regulatory milestones and timelines, or the inconvenience to patients; the adoption of XPOVIO in the commercial market, the timing and costs of commercializing XPOVIO or any of Karyopharm's drug candidates receiving regulatory approval; the ability to obtain and maintain regulatory approval of XPOVIO or any of Karyopharm's drug candidates receiving regulatory approval; the results of Karyopharm's clinical trials and preclinical studies, including post-analysis of existing data and new data received from ongoing and future studies; the content and timing of decisions made by the US Food and Drug Administration and other regulatory authorities, research review boards at clinical trial sites, and publication review bodies, including with respect to the need for additional clinical studies; the ability of Karyopharm or its third party collaborators or successors in interest to fully perform their respective obligations under the applicable agreement and the potential future financial implications of such agreement; Karyopharm's ability to enroll patients in its clinical trials; unexpected cash needs and expenses; the development or regulatory approval of drug candidates by Karyopharm's competitors for products or product candidates that Karyopharm is currently marketing or developing; and Karyopharm's ability to obtain, maintain and enforce patent and other intellectual property protection for any of its products or product candidates. These and other risks are described under the heading "Risk Factors" in Karyopharm's Quarterly Report on Form 10-Q for the quarter ended June 30, 2022, which was filed with the Securities and Exchange Commission (SEC). on August 4, 2022, and in other filings that Karyopharm may make with the SEC in the future. Any forward-looking statement contained in this press release speaks only as of the date hereof, and, except as required by law, Karyopharm expressly disclaims any obligation to update any forward-looking statement, whether as a result of new information, future events or other type.
XPOVIO® and NEXPOVIO® are registered trademarks of Karyopharm Therapeutics Inc. Any other trademarks referenced in this release are the property of their respective owners.
1 NORD, Rare Disease Database, Primary Myelofibrosis, Accessed 4/10/22, link
View original content: enlace