PR97134

Karyopharm and Menarini Group Receive Full Marketing Authorisation from the European Commission for NEXPOVIO(R) (selinexor) for the Treatment of Patients with Multiple Myeloma After at Least One Prior Therapy

NEWTON, Mass. and FLORENCE, Italy, July 21, 2022 /PRNewswire=KYODO JBN/ --

– Based on Results from Phase 3 BOSTON Study, Marketing Authorisation Expands

Multiple Myeloma Indication –

– Approval Follows Positive Opinion by European Committee for Medicinal

Products for Human Use (CHMP) in May 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, today announced

that the European Commission (EC) has granted Marketing Authorisation for

NEXPOVIO(R) (selinexor), a first-in-class, oral exportin 1 (XPO1) inhibitor, in

combination with once-weekly bortezomib (Velcade(R)) and low-dose dexamethasone

(SVd) for the treatment of adults with multiple myeloma who have received at

least one prior therapy. With this approval for the extension of NEXPOVIO(R)'s

indication in the European Union (EU), the conditional marketing authorisation

is now converted to a full approval. The marketing authorisation, which marks

the second indication for NEXPOVIO(R), is valid in all 27 member states of the

EU as well as Iceland, Liechtenstein, Norway, and Northern Ireland. Stemline

Therapeutics B.V., a wholly owned subsidiary of the Menarini Group, will be

responsible for all commercialization activities in Europe.

The approval follows a positive opinion granted in May 2022 by the CHMP based

on results from the Phase 3 BOSTON study that demonstrated once-weekly SVd

resulted in a statistically significant reduction in the risk of disease

progression or death compared to standard twice-weekly bortezomib plus

dexamethasone (Vd) regimen. The results from the BOSTON study were published in

The Lancet (Grosicki, et al.) in November 2020.

"The European Commission's approval of an expanded use of NEXPOVIO(R) provides

another option for patients with multiple myeloma who have relapsed, or become

resistant to current treatment regimens," said Richard Paulson, President and

Chief Executive Officer of Karyopharm. "Our decision to pursue approval for

this patient population is indicative of our commitment to expand access to

selinexor across the globe and we look forward to working closely with Menarini

who will commercialize NEXPOVIO(R) in Europe."

"The approval of NEXPOVIO(R) marks an important step forward for patients in

Europe where nearly 51,000 new cases of multiple myeloma are diagnosed each

year and therapeutic options are limited," said Elcin Barker Ergun, Chief

Executive Officer of Menarini. "We are committed to offering patients and

physicians a valuable new treatment option and are working hard to make

NEXPOVIO(R) available in different European countries as quickly as possible."

About the BOSTON study  

The Marketing Authorisation is based upon the Phase 3 BOSTON (Bortezomib,

Selinexor and Dexamethasone) study, which was a multi-center, randomized study

(NCT03110562) that evaluated 402 adult patients with relapsed or refractory

multiple myeloma who had received one to three prior lines of therapy. The

study was designed to compare the efficacy, safety and certain health-related

quality of life parameters of once-weekly SVd versus twice-weekly Vd. The

primary endpoint of the study was progression-free survival and key secondary

endpoints included overall response rate, rate of peripheral neuropathy, and

others. To learn more about this study, please refer to  Karyopharm and

Menarini's press release on the positive CHMP opinion issued on May 20, 2022.

About Multiple Myeloma in Europe

Multiple myeloma is an incurable cancer with significant morbidity and the

second most common hematologic malignancy. According to the World Health

Organization, in 2020, there were approximately 51,000 new cases and 32,000

deaths from multiple myeloma in Europe1. While the treatment of multiple

myeloma has improved over the last 20 years, and overall survival has increased

considerably, the disease remains incurable, and nearly all patients will

eventually relapse and develop disease that is refractory to all approved

anti-myeloma therapies. Therefore, there continues to be a high unmet medical

need for new therapies, particularly those with novel mechanisms of action.

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 expanded NEXPOVIO(R) indication now allows adult patients with multiple

myeloma to be treated in earlier lines of therapy. The indication for

NEXPOVIO(R) is valid in the EU Member States as well as Iceland, Liechtenstein,

Norway, and Northern Ireland. NEXPOVIO(R) is also approved in the UK under a

Conditional Marketing Authorisation. The extension of indication in combination

with bortezomib and dexamethasone for the treatment of adults with multiple

myeloma who have received at least one prior therapy is currently under review

by Medicines and Healthcare Products Regulatory Agency.

NEXPOVIO(R) is a first-in-class, oral exportin 1 (XPO1) inhibitor. NEXPOVIO(R)

functions by selectively binding to and inhibiting the nuclear export protein

exportin 1 (XPO1, also called CRM1). NEXPOVIO(R) 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(R) Summary of Product Characteristics and European Public

Assessment Report at

https://ec.europa.eu/health/documents/community-register/html/h1537.htm

UNITED STATES 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(R).

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 (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

www.karyopharm.com, 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 www.menarini.com.

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 adult

patients with multiple myeloma, the commercial launch of NEXPOVIO(R) in Europe,

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 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 March 31, 2022, which was filed with the Securities and Exchange

Commission (SEC) on May 5, 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.

References

[1] World Health Organization. 2020.

https://gco.iarc.fr/today/data/factsheets/cancers/35-Multiple-myeloma-fact-sheet.pdf

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Source: Menarini Industrie Farmaceutiche Riunite