On December 21, 2021 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, reported their entry into an exclusive licensing agreement whereby Menarini will commercialize NEXPOVIO, Karyopharm’s first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound, in Europe and other key global territories (Press release, Karyopharm, DEC 21, 2021, View Source [SID1234597531]).
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Under the terms of the agreement, Menarini received exclusive rights to commercialize NEXPOVIO for the treatment of oncology indications in the European Union and other European countries (including the United Kingdom), Latin America and other key countries. In exchange, Karyopharm will receive an upfront payment of $75 million (USD) in 2021 and is eligible to receive up to an additional $202.5 million in future milestones, plus tiered double-digit royalties on net sales of NEXPOVIO in the licensed territories.
"Menarini is a global pharmaceutical company, with a strong heritage and footprint in Europe and an unwavering commitment to patients, that is dedicated to innovation and bringing new treatment options in oncology. Menarini is an ideal partner to maximize selinexor’s potential to have a positive impact on the treatment of cancer in Europe, Latin America and other key countries and this transaction marks an important step forward toward that goal," said Richard Paulson, President and Chief Executive Officer of Karyopharm. "With a shared vision on the potential of selinexor and Menarini’s commercialization expertise, this agreement aligns our two companies with the common goal of expanding the number of patients who can access NEXPOVIO in these important global territories."
"We are delighted to partner with Karyopharm to provide NEXPOVIO in Europe, Latin America and other key countries in the world," said Elcin Barker Ergun, Chief Executive Officer of the Menarini Group. "Patients suffering from multiple myeloma continuously need different options as resistance develops to first line therapies and the unique mechanism of action of selinexor makes it an ideal partner as a backbone therapy in second line and beyond. The potential further expansion of NEXPOVIO in solid tumors, such as in endometrial cancers, where limited options exist, underline the wide potential of selinexor in playing a role in cancer treatments aligning well with our mission of providing therapies that can prolong patient lives."
NEXPOVIO has received conditional marketing authorization from 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. The European Medicines Agency (EMA) has validated the Marketing Authorization Application (MAA) for NEXPOVIO in combination with Velcade (bortezomib) and low-dose dexamethasone for the treatment of multiple myeloma following at least one prior therapy. The MAA will be reviewed by the Committee for Medicinal Products for Human Use (CHMP), which will issue an opinion to the European Commission regarding the potential approval for the expanded indication. This review is expected to be completed during the first half of 2022.
About NEXPOVIO (selinexor)
NEXPOVIO, which is marketed as XPOVIO in the U.S., is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound. 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 (selinexor) 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 as well as The EEA Countries of Iceland, Liechtenstein and Norway
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 (≥30%) of selinexor in combination with dexamethasone were nausea, thrombocytopenia, fatigue, anaemia, decreased appetite, decreased weight, diarrhoea, vomiting, hyponatraemia, neutropenia and leukopenia.
The most commonly reported serious adverse reactions (≥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.