PR96116

 

NEWTON, Mass. and FLORENCE, Italy, May 20, 2022 /PRNewswire=KYODO JBN/ --

 

-- European Commission Decision Anticipated within Approximately 60 Days --

 

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 Medicines Agency's (EMA) Committee for Medicinal Products for

Human Use (CHMP) has adopted a positive opinion recommending approval of

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 one

to three prior lines of therapy.

 

The positive CHMP opinion is a scientific recommendation for marketing

authorization and one of the final steps before the European Commission (EC)

makes a decision on Karyopharm's NEXPOVIO application. The EC's decision is

expected within approximately 60 days following the CHMP recommendation. In

December 2021, Karyopharm and Menarini Group entered into an exclusive license

agreement to commercialize NEXPOVIO(R) (selinexor) in Europe.

 

"Despite therapeutic advances, multiple myeloma remains an incurable disease

that is difficult to treat," said Richard Paulson, President and Chief

Executive Officer of Karyopharm. "Today's positive CHMP opinion brings us one

step closer to our goal of making NEXPOVIO available to patients globally who

may benefit from its novel mechanism of action. We are pleased to have Menarini

as a partner in this effort given its commercialization expertise as well as

strong heritage and footprint in Europe."

 

"We are thrilled with the CHMP's recommendation in favor of NEXPOVIO and what

it represents for multiple myeloma patients in need of new and innovative

treatment options," said Elcin Barker Ergun, Chief Executive Officer of

Menarini. "Pending potential marketing authorization from the EC, we will work

closely with appropriate authorities to ensure this important treatment can be

made available to patients in Europe."

 

Karyopharm's application is supported by data from the Phase 3 BOSTON study,

which evaluated the SVd triplet regimen in patients with relapsed or refractory

multiple myeloma and were published in The Lancet (Grosicki, et al.) in

November 2020. This CHMP opinion follows the approval of XPOVIO(R) (selinexor)

by the U.S. Food and Drug Administration in December 2020 in the SVd

combination in patients with multiple myeloma after at least one prior therapy.

 

About the Pivotal Phase 3 BOSTON Study

 

The Phase 3 BOSTON (Bortezomib, Selinexor and Dexamethasone) study was an

multi-center, randomized study (NCT03110562), which 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 bortezomib and low-dose dexamethasone (Vd). The primary

endpoint of the study was progression-free survival (PFS) and key secondary

endpoints included overall response rate (ORR), rate of peripheral neuropathy,

and others. Additionally, the BOSTON study allowed for patients on the Vd

control arm to crossover to the SVd arm following objective (quantitative)

progression of disease verified by an Independent Review Committee (IRC). The

BOSTON study was conducted at over 150 clinical sites internationally.

 

Despite the study having a high proportion of patients with high-risk

cytogenetics (~50%) compared to other Velcade®-based studies in previously

treated myeloma, the median PFS in the SVd arm was 13.93 months compared to

9.46 months in the Vd arm, representing a 4.47 month (47%) increase in median

PFS (hazard ratio (HR)=0.70; p=0.0075). The SVd arm also demonstrated a

significantly greater ORR compared to the Vd arm (76.4% vs. 62.3%, p=0.0012).

Patients who had received only one prior line of therapy also demonstrated a

higher ORR on the SVd arm as compared to the Vd arm (80.8% vs. 65.7%,

p=0.0082). Importantly, SVd therapy compared to Vd therapy showed consistent

PFS benefit and higher ORR across several important subgroups.

 

In addition, the following results favored SVd therapy as compared to Vd

therapy:

 

SVd therapy demonstrated a significantly higher rate of deep responses, defined

as greater than or equal to very Good Partial Response compared to Vd therapy

(44.6% vs. 32.4%) as well as a longer median duration of response (20.3 months

vs. 12.9 months). Additionally, 16.9% of patients on the SVd arm achieved a

complete response or a stringent complete response as compared to 10.6% of

patients receiving Vd therapy.  All responses were confirmed by an IRC.

Data as of the cut-off date of February 15, 2021 showed a trend toward an

overall survival (OS) benefit associated with SVd therapy with fewer deaths,

numerically, reported on the SVd arm (68 vs. 80). Median OS for the SVd arm was

36.7 months, while the median OS for the Vd arm was 32.8 months.

Peripheral neuropathy (PN) rates were significantly lower on SVd compared to Vd

(32.3% vs. 47.1%; p=0.0010). In addition, PN rates of grade greater than or

equal to 2 were also significantly lower in the SVd arm compared to Vd (21.0%

vs. 34.3%, P=0.0013).

 

The most common adverse events (AEs; greater than or equal to 20%) were

cytopenias, along with gastrointestinal and constitutional symptoms and were

consistent with those previously reported from other selinexor studies. Most

AEs were manageable with dose modifications and/or standard supportive care.

The most common non-hematologic AEs were fatigue (59%), nausea (50%), decreased

appetite (35%), diarrhea (32%), peripheral neuropathy (32%), upper respiratory

tract infection (29%), decreased weight (26%), cataract (22%) and vomiting

(21%) and were mostly Grade 1 and 2 events. The most common Grade 3 and 4 AEs

(greater than or equal to 10%) were thrombocytopenia, lymphopenia,

hypophosphatemia, anemia, hyponatremia and neutropenia.

 

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, which is marketed as XPOVIO in the U.S., 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 fashion. NEXPOVIO has been granted

conditional marketing authorization by the European Commission 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.

 

Therapeutic indication for NEXPOVIO in the EU Member States as well as Iceland,

Liechtenstein, Norway and Northern Ireland.  NEXPOVIO is also approved in the

UK under a Conditional Marketing Authorisation.

 

NEXPOVIO is indicated 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.

 

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.

 

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.

 

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 authorization 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.

 

Please see NEXPOVIO Summary of Product Characteristics and European Public

Assessment Report at

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

 

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 and Singapore. Karyopharm

has a focused pipeline targeting multiple high unmet need cancer indications,

including in 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

[https://twitter.com/Karyopharm ] and LinkedIn

[https://www.linkedin.com/company/karyopharm/ ].

 

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.

 

Menarini has a deep commitment for developing treatments addressing oncological

and hematologic diseases. Menarini actively develops Elzonris (marketed in US

and Europe for BPDCN) for multiple hematologic malignancies, including AML,

CMML and myelofibrosis, and elacestrant and felezenexor for oncology as well.

Additionally, the FDA recently granted MEN1703 an orphan drug designation for

AML. 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 potential approval and commercial launch

of NEXPOVIO in the European Union[Europe]; 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 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

 

 

Logo - https://mma.prnewswire.com/media/652491/MENARINI_Group_Logo.jpg

 

SOURCE: Menarini Industrie Farmaceutiche Riunite