Country for PR: United Kingdom
Contributor: PR Newswire Europe
Tuesday, November 01 2022 - 23:02
Karyopharm and Menarini Group Announce Orphan Medicinal Product Designation from the European Commission for Selinexor for the Treatment of Myelofibrosis
NEWTON, Mass. and FLORENCE, Italy, Nov. 1, 2022 /PRNewswire-AsiaNet/ --

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, today announced 
that the European Commission (EC) has granted orphan medicinal product 
designation for selinexor for the treatment of myelofibrosis (MF). 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(R) 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.

"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(R) (selinexor)
NEXPOVIO(R), which is marketed as XPOVIO(R) 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 

Please see NEXPOVIO(R) Summary of Product Characteristics and European Public 
Assessment Report at

Please refer to local prescribing information where XPOVIO/NEXPOVIO is approved 
for full 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 

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.

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.

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.

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.

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.

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 

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 (greater than or equal to 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 (greater than or equal to 
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.

About Karyopharm Therapeutics
Karyopharm Therapeutics Inc. (NASDAQ: KPTI) is a commercial-stage 
pharmaceutical company pioneering novel cancer therapies. Since its founding, 
Karyopharm has been the industry leader in oral Selective Inhibitor of Nuclear 
Export (SINE) compound technology, which was developed to address a fundamental 
mechanism of oncogenesis: nuclear export dysregulation. Karyopharm's lead SINE 
compound and first-in-class, oral exportin 1 (XPO1) inhibitor, XPOVIO(R) 
(selinexor), is approved in the U.S. and marketed by the Company in three 
oncology indications and has received regulatory approvals in various 
indications in a growing number of ex-U.S. territories and countries, including 
Europe and the United Kingdom (as NEXPOVIO(R)), China, Singapore, Canada, 
Israel, South Korea, and Australia. Karyopharm has a focused pipeline targeting 
multiple high unmet need cancer indications, including in multiple myeloma, 
endometrial cancer, myelodysplastic syndromes and myelofibrosis. For more 
information about our people, science and pipeline, please visit, and follow us on Twitter at @Karyopharm and LinkedIn.

About Menarini Group
The Menarini Group is a leading international pharmaceutical and diagnostics 
company, with a turnover of over $4 billion and over 17,000 employees. Menarini 
is focused on therapeutic areas with high unmet needs with products for 
oncology, cardiology, pneumology, gastroenterology, infectious diseases, 
diabetology, inflammation, and analgesia. With 18 production sites and 9 
Research and Development centers, Menarini's products are available in 140 
countries worldwide. For further information, please visit 
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 related to future clinical development 
and potential regulatory submissions of selinexor. Such statements are subject 
to numerous important factors, risks and uncertainties, many of which are 
beyond Karyopharm's control, that may cause actual events or results to differ 
materially from Karyopharm's current expectations. For example, there can be no 
guarantee that Karyopharm will successfully commercialize XPOVIO(R); or that 
any of Karyopharm's drug candidates, including selinexor and eltanexor, will 
successfully complete necessary clinical development phases or that development 
of any of Karyopharm's drug candidates will continue. Further, there can be no 
guarantee that any positive developments in the development or 
commercialization of Karyopharm's drug candidate portfolio will result in stock 
price appreciation. Management's expectations and, therefore, any 
forward-looking statements in this press release could also be affected by 
risks and uncertainties relating to a number of other factors, including the 
following: the risk that the COVID-19 pandemic could disrupt Karyopharm's 
business more severely than it currently anticipates, including by negatively 
impacting sales of XPOVIO, interrupting or delaying research and development 
efforts, impacting the ability to procure sufficient supply for the development 
and commercialization of selinexor or other product candidates, delaying 
ongoing or planned clinical trials, impeding the execution of business plans, 
planned regulatory milestones and timelines, or inconveniencing patients; the 
adoption of XPOVIO in the commercial marketplace, the timing and costs involved 
in commercializing XPOVIO or any of Karyopharm's drug candidates that receive 
regulatory approval; the ability to obtain and retain regulatory approval of 
XPOVIO or any of Karyopharm's drug candidates that receive regulatory approval; 
Karyopharm's results of clinical trials and preclinical studies, including 
subsequent analysis of existing data and new data received from ongoing and 
future studies; the content and timing of decisions made by the U.S. Food and 
Drug Administration and other regulatory authorities, investigational 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; unplanned cash requirements and expenditures; 
development or regulatory approval of drug candidates by Karyopharm's 
competitors for products or product candidates in which Karyopharm is currently 
commercializing 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 
caption "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 statements contained in 
this press release speak only as of the date hereof, and, except as required by 
law, Karyopharm expressly disclaims any obligation to update any 
forward-looking statements, whether as a result of new information, future 
events or otherwise.

XPOVIO(R) and NEXPOVIO(R) are registered trademarks of Karyopharm Therapeutics 
Inc. Any other trademarks referred to in this release are the property of their 
respective owners.

1 NORD, Rare Disease Database, Primary Myelofibrosis, Accessed on 10/4/22,


SOURCE: Menarini Industrie Farmaceutiche Riunite