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- Karyopharm and Menarini Group receive full marketing authorization from the UK Medicines and Healthcare Products Regulatory Agency for NEXPOVIO® (selinexor) in combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy
– Based on Phase 3 BOSTON Study Results, Marketing Authorization Expands Multiple Myeloma Indication –
NEWTON, Mass. and FLORENCE, Italy, Feb. 22, 2023 /PRNewswire/ -- Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, and Menarini Group ("Menarini" ), a leading privately-owned international pharmaceutical company, today announced that the UK's Medicines and Healthcare Products Regulatory Agency (MHRA) has granted full Marketing Authorization for NEXPOVIO® (selinexor), an oral exportin-1 inhibitor ( XPO1), the first of its kind, 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. With this approval extending the indication for NEXPOVIO in Great Britain, the conditional marketing authorization now becomes full approval. Stemline Therapeutics B.V., a 100% subsidiary of the Menarini Group, will be responsible for all commercialization activities in the UK.
The approval is based on the results of the phase 3 BOSTON study, which demonstrated that once-weekly SVd resulted in a statistically significant reduction in the risk of disease progression or death compared with the standard regimen of bortezomib plus dexamethasone. (Vd) twice a week. The results of 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 CEO of Karyopharm. "We are delighted to extend the positive impact of NEXPOVIO to people living with multiple myeloma in Britain and continue to work to further expand access to selinexor around the world."
"We are pleased with the MHRA's decision to extend the NEXPOVIO indication in Great Britain, bringing this important medicine to more people with myeloma who may benefit from it," said Elcin Barker Ergun, CEO of Menarini. "We look forward to supplying NEXPOVIO to patients and physicians in Great Britain as soon as possible."
About the BOSTON Study The marketing authorization is based on the Phase 3 BOSTON (Bortezomib, Selinexor, and Dexamethasone) study, which was a randomized, multicenter study ( NCT03110562) evaluating 402 adult patients with relapsed or refractory multiple myeloma who they had received one to three prior lines of treatment. The study was designed to compare the efficacy, safety, and certain health-related quality of life parameters of SVd once weekly versus Vd twice weekly. The study's primary endpoint was progression-free survival, and key secondary endpoints included overall response rate, peripheral neuropathy rate, and others. For more information about this study, see the press release announcing the publication of the BOSTON study results in The Lancet, published on November 12, 2020.
About NEXPOVIO® (selinexor)NEXPOVIO®, which is marketed as XPOVIO® in the US, has been approved by the European Commission for the following oncology indications: (i) in combination with dexamethasone for the treatment of multiple myeloma in patients adults 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 adult patients 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 and Austria from the fourth quarter of 2022.
NEXPOVIO® is an oral exportin 1 (XPO1) inhibitor, the first of its kind. 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 regulatory, and anti-inflammatory proteins, leading to the accumulation of these proteins in the nucleus and potentiating their anticancer activity in the cell. Forced nuclear retention of these proteins can counteract a multitude of oncogenic pathways that, left unchecked, allow cancer cells with severe DNA damage to continue to grow and divide uncontrollably.
See the NEXPOVIO® Summary of Product Characteristics and the European Public Assessment Report at https://ec.europa.eu/health/documents/community-register/html/h1537.htm
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 in patients at risk of dehydration.
Concomitant prophylactic treatment with a 5-HT3 antagonist and/or other anti-nausea agents should be provided prior to and during treatment with NEXPOVIO®.
Hematology:
Complete blood count (CBC) of patients should be assessed at baseline, during treatment, and as clinically indicated. Monitor more frequently during the first two months of treatment.
Thrombocytopenia:
Thrombocytopenic events (thrombocytopenia and decreased platelet count) were commonly reported in adult patients receiving selinexor and may be serious (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, diarrhea, which can sometimes be severe and may require the use of antiemetic and antidiarrheal drugs.
Weight loss and anorexia:
Patients should be monitored for body weight, nutritional status, and volume at baseline, during treatment, and when clinically indicated. Monitoring should be more frequent during the first two months of treatment.
Confused state and dizziness:
Patients should be instructed to avoid situations where dizziness or confusion may be a problem and not to take other medicinal products that may cause dizziness or confusion without appropriate medical advice. Patients should be advised not to drive or operate heavy machinery until symptoms resolve.
Hyponatremia:
Patients should have their sodium levels monitored at baseline, during treatment, and when clinically indicated. Monitoring should be more frequent during the first two months of treatment.
Waterfalls:
Selinexor may cause new onset or exacerbation of cataracts. Ophthalmologic evaluation may be performed as clinically indicated. The 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. Patients at high risk for TLS should be carefully monitored. Quickly deal with TLS in accordance with institutional guidelines.
Fertility, pregnancy and lactation
Women of childbearing potential/contraception in men and women:
Females of childbearing potential and adult male patients of reproductive potential should be advised to use effective contraception or to refrain from sexual intercourse while taking selinexor and for at least 1 week after 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.
Lactation:
It is not known whether selinexor or its metabolites are excreted in human milk. A risk to nursing children cannot be excluded. Breast-feeding should be discontinued during treatment with selinexor and for 1 week after the last dose.
unwanted effects
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 frequently reported infections, with 25% of reported infections being serious, and fatal infections occurring in 3% of adult patients treated.
elderly population
Patients 75 years 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
The notification of suspected adverse reactions after the authorization of the medicinal product is important. It allows continuous monitoring of the benefit/risk balance of the drug. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.
About Karyopharm Therapeutics Karyopharm Therapeutics Inc. (Nasdaq: KPTI) is a commercial-stage pharmaceutical company pioneering novel cancer therapies. Since its founding, Karyopharm has been an industry leader in selective nuclear export inhibitor (SINE) oral compound technology, developed to address a key mechanism of oncogenesis: dysregulation of nuclear export. Karyopharm's lead SINE compound and first-in-class oral exportin 1 (XPO1) inhibitor, XPOVIO® (selinexor), is approved in the US and marketed by the company in three oncology indications, and has received regulatory approvals in various indications in a growing number of territories and countries outside the US, including Europe and the UK (as NEXPOVIO®), China, Singapore, Canada, Israel, South Korea and Australia. Karyopharm has a portfolio of projects focused on multiple unmet high-need cancer indications, including multiple myeloma, endometrial cancer, myelodysplastic syndromes, and myelofibrosis. For more information about our people, our science, and our projects, visit www.karyopharm.com, and follow us on Twitter at @Karyopharm and LinkedIn.
About Menarini Group Menarini Group is a leading international pharmaceutical and diagnostics company with revenues of more than $4 billion 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. These forward-looking statements include statements regarding the ability of selinexor to treat patients with multiple myeloma; expectations regarding the commercial launch of NEXPOVIO in the UK; and expectations regarding future clinical development plans and potential regulatory filings for selinexor. Such statements are subject to numerous important factors, risks and uncertainties, many of which are beyond the control of Karyopharm, which may cause actual events or results to differ materially from Karyopharm's current expectations. For example, there can be no assurance that Karyopharm will successfully commercialize 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 guarantee that any positive developments in the development or commercialization of Karyopharm's portfolio of drug candidates will translate into any appreciation of the share price. Management's expectations, and therefore any forward-looking statements contained in this press release, may be affected by risks and uncertainties related to other factors, including, but not limited to: the risk that the COVID-19 pandemic may disrupt Karyopharm's business more severely than currently anticipated, including adversely affecting sales of XPOVIO, interrupt or delay research and development efforts, affect the ability to obtain sufficient supply for development and commercialization of selinexor or other candidate products, delay ongoing or planned clinical trials, hinder the execution of business plans, expected regulatory milestones and timelines, or cause inconvenience to patients; the commercial market adoption of XPOVIO, the timing and costs to market of XPOVIO or any of Karyopharm's drug candidates receiving regulatory approval; the ability to obtain and maintain regulatory approval for 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 of clinical trial sites, and publication review bodies, including with respect to the need for further 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; unforeseen treasury needs and expenses; the development or regulatory approval of drug candidates by Karyopharm's competitors for products or drug candidates that Karyopharm is currently developing or marketing; and Karyopharm's ability to obtain, maintain and enforce patent and other intellectual property rights protection for any of its products or drug candidates. These and other risks are described under the heading "Risk Factors" in Karyopharm's Annual Report on Form 10-K for the year ended December 31, 2022, which was filed with the Securities and Exchange Commission (SEC) on February 17, 2023, and in other documents that Karyopharm may file with the SEC in the future. All forward-looking statements contained in this press release are valid 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 reasons.
XPOVIO® and NEXPOVIO® are registered trademarks of Karyopharm Therapeutics Inc. All other trademarks referenced in this release are the property of their respective owners.
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