— European Commission Decision Anticipated by April 2021 —
NEWTON, MA, USA I January 29, 2021 I Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending the conditional approval for NEXPOVIO® (selinexor) 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 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 marketing authorization application (MAA). An EC marketing authorization through the centralized procedure is valid in all 27 European Union member countries as well as the European Economic Area countries Iceland, Liechtenstein and Norway.
“We are delighted that the CHMP has adopted a positive opinion for NEXPOVIO, which could lead to Karyopharm’s first regulatory approval in Europe,” said Sharon Shacham, PhD, MBA, Founder, President and Chief Scientific Officer of Karyopharm. “This positive opinion highlights the CHMP’s recognition of the positive clinical benefit-risk profile for oral NEXPOVIO and takes Karyopharm one step closer to bringing this important medicine to European patients in need of novel multiple myeloma treatment options. We look forward to the European Commission’s final decision on the NEXPOVIO MAA, which is expected by April of 2021.”
The MAA is supported by data from the Phase 2b STORM study which evaluated selinexor in patients with heavily pretreated, triple class refractory multiple myeloma and published in the New England Journal of Medicine (Chari, et al.) in August 2019.
Karyopharm intends to submit a second regulatory filing to the EMA (Type II variation) by April 2021 based on the data from the confirmatory Phase 3 BOSTON study, which evaluated once-weekly NEXPOVIO in combination with once-weekly Velcade® and low-dose dexamethasone in patients with multiple myeloma after at least one prior therapy with the goal of further expanding the global reach of NEXPOVIO to additional patients in need of new treatment options.
About the Phase 2b STORM Pivotal Trial
The Phase 2b STORM trial (Selinexor Treatment of Refractory Myeloma) was an international, multi-center, single-arm, open-label study which enrolled 122 patients (Part 2 of the trial) with heavily pretreated, triple class refractory multiple myeloma. Patients in the trial had a median of seven previous therapeutic regimens, including a median of 10 unique antimyeloma agents.
For the study’s primary endpoint, oral selinexor achieved an overall response rate of 26% (95% confidence interval [CI], 19, 35) and the trial therefore met its primary endpoint. Minimal response per IMWG criteria was observed in 16 (13%) patients and 48 patients (39%) had stable disease. All responses were adjudicated by an Independent Review Committee. The median overall survival was 8.6 months in the total population studied and 15.6 months in patients who had a minimal response or better.
Karyopharm’s request for conditional approval in Europe is based upon the same patient population that served as the basis for XPOVIO’s accelerated FDA approval in the U.S. Specifically, it includes the efficacy and safety data from a pre-specified sub-group analysis of 83 patients in the STORM study whose disease was refractory to bortezomib, carfilzomib, lenalidomide, pomalidomide, and daratumumab, as the benefit-risk ratio appeared to be greater in this more heavily pre-treated population than in the overall trial population. The overall response rate in this patient population was 25.3%.
The most common adverse reactions (≥20%) were thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea and upper respiratory tract infection. In the STORM trial, fatal adverse reactions occurred in 9% of patients. Serious adverse reactions occurred in 58% of patients. Treatment discontinuation rate due to adverse reactions was 27%.
About Multiple Myeloma in Europe
Multiple myeloma (MM) is an incurable cancer with significant morbidity and the second most common hematologic malignancy. In 2020, there were approximately 51,000 new cases and 32,000 deaths from MM in Europe1. While the treatment of MM 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-MM therapies. Therefore, there continues to be a high unmet medical need for new therapies, particularly those with novel mechanisms of action.
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. XPOVIO is approved in the U.S. in multiple hematologic malignancy indications, including in combination with Velcade® (bortezomib) and dexamethasone for the treatment of patients with multiple myeloma after at least one prior therapy, in combination with dexamethasone for the treatment of patients with heavily pretreated multiple myeloma and as a monotherapy for the treatment of patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy. A Marketing Authorization Application for NEXPOVIO for patients with penta-refractory multiple myeloma is also currently under review by the European Medicines Agency and received a positive CHMP opinion in January 2021. Selinexor is also being evaluated in several other mid-and later-phase clinical trials across multiple cancer indications, including as a potential backbone therapy in combination with approved myeloma therapies (STOMP), in liposarcoma (SEAL) and in endometrial cancer (SIENDO), among others. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or currently planned, including multiple studies in combination with approved therapies in a variety of tumor types to further inform Karyopharm’s clinical development priorities for selinexor. Additional clinical trial information for selinexor is available at www.clinicaltrials.gov.
For more information about Karyopharm’s products or clinical trials, please contact the Medical Information department at:
Tel: +1 (888) 209-9326
Email: medicalinformation@karyopharm.com
For additional product information, including full prescribing information, please visit www.XPOVIO.com.
About Karyopharm Therapeutics
Karyopharm Therapeutics Inc. (Nasdaq: KPTI) is a commercial-stage pharmaceutical company pioneering novel cancer therapies and dedicated to the discovery, development, and commercialization of novel first-in-class drugs directed against nuclear export and related targets for the treatment of cancer and other major diseases. Karyopharm’s Selective Inhibitor of Nuclear Export (SINE) compounds function by binding with and inhibiting the nuclear export protein XPO1 (or CRM1). Karyopharm’s lead compound, XPOVIO® (selinexor), is approved in the U.S. in multiple hematologic malignancy indications, including in combination with Velcade® (bortezomib) and dexamethasone for the treatment of patients with multiple myeloma after at least one prior therapy, in combination with dexamethasone for the treatment of patients with heavily pretreated multiple myeloma and as a monotherapy for the treatment of patients with relapsed or refractory diffuse large B-cell lymphoma. A Marketing Authorization Application for NEXPOVIO™ (selinexor) for patients with heavily pretreated multiple myeloma is also currently under review by the European Medicines Agency. In addition to single-agent and combination activity against a variety of human cancers, SINE compounds have also shown biological activity in models of neurodegeneration, inflammation, autoimmune disease, certain viruses and wound-healing. Karyopharm has several investigational programs in clinical or preclinical development. For more information, please visit www.karyopharm.com.
References
1 World Health Organization. 2020. https://gco.iarc.fr/today/data/factsheets/cancers/35-Multiple-myeloma-fact-sheet.pdf
SOURCE: Karyopharm Therapeutics
Post Views: 625
— European Commission Decision Anticipated by April 2021 —
NEWTON, MA, USA I January 29, 2021 I Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending the conditional approval for NEXPOVIO® (selinexor) 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 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 marketing authorization application (MAA). An EC marketing authorization through the centralized procedure is valid in all 27 European Union member countries as well as the European Economic Area countries Iceland, Liechtenstein and Norway.
“We are delighted that the CHMP has adopted a positive opinion for NEXPOVIO, which could lead to Karyopharm’s first regulatory approval in Europe,” said Sharon Shacham, PhD, MBA, Founder, President and Chief Scientific Officer of Karyopharm. “This positive opinion highlights the CHMP’s recognition of the positive clinical benefit-risk profile for oral NEXPOVIO and takes Karyopharm one step closer to bringing this important medicine to European patients in need of novel multiple myeloma treatment options. We look forward to the European Commission’s final decision on the NEXPOVIO MAA, which is expected by April of 2021.”
The MAA is supported by data from the Phase 2b STORM study which evaluated selinexor in patients with heavily pretreated, triple class refractory multiple myeloma and published in the New England Journal of Medicine (Chari, et al.) in August 2019.
Karyopharm intends to submit a second regulatory filing to the EMA (Type II variation) by April 2021 based on the data from the confirmatory Phase 3 BOSTON study, which evaluated once-weekly NEXPOVIO in combination with once-weekly Velcade® and low-dose dexamethasone in patients with multiple myeloma after at least one prior therapy with the goal of further expanding the global reach of NEXPOVIO to additional patients in need of new treatment options.
About the Phase 2b STORM Pivotal Trial
The Phase 2b STORM trial (Selinexor Treatment of Refractory Myeloma) was an international, multi-center, single-arm, open-label study which enrolled 122 patients (Part 2 of the trial) with heavily pretreated, triple class refractory multiple myeloma. Patients in the trial had a median of seven previous therapeutic regimens, including a median of 10 unique antimyeloma agents.
For the study’s primary endpoint, oral selinexor achieved an overall response rate of 26% (95% confidence interval [CI], 19, 35) and the trial therefore met its primary endpoint. Minimal response per IMWG criteria was observed in 16 (13%) patients and 48 patients (39%) had stable disease. All responses were adjudicated by an Independent Review Committee. The median overall survival was 8.6 months in the total population studied and 15.6 months in patients who had a minimal response or better.
Karyopharm’s request for conditional approval in Europe is based upon the same patient population that served as the basis for XPOVIO’s accelerated FDA approval in the U.S. Specifically, it includes the efficacy and safety data from a pre-specified sub-group analysis of 83 patients in the STORM study whose disease was refractory to bortezomib, carfilzomib, lenalidomide, pomalidomide, and daratumumab, as the benefit-risk ratio appeared to be greater in this more heavily pre-treated population than in the overall trial population. The overall response rate in this patient population was 25.3%.
The most common adverse reactions (≥20%) were thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea and upper respiratory tract infection. In the STORM trial, fatal adverse reactions occurred in 9% of patients. Serious adverse reactions occurred in 58% of patients. Treatment discontinuation rate due to adverse reactions was 27%.
About Multiple Myeloma in Europe
Multiple myeloma (MM) is an incurable cancer with significant morbidity and the second most common hematologic malignancy. In 2020, there were approximately 51,000 new cases and 32,000 deaths from MM in Europe1. While the treatment of MM 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-MM therapies. Therefore, there continues to be a high unmet medical need for new therapies, particularly those with novel mechanisms of action.
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. XPOVIO is approved in the U.S. in multiple hematologic malignancy indications, including in combination with Velcade® (bortezomib) and dexamethasone for the treatment of patients with multiple myeloma after at least one prior therapy, in combination with dexamethasone for the treatment of patients with heavily pretreated multiple myeloma and as a monotherapy for the treatment of patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy. A Marketing Authorization Application for NEXPOVIO for patients with penta-refractory multiple myeloma is also currently under review by the European Medicines Agency and received a positive CHMP opinion in January 2021. Selinexor is also being evaluated in several other mid-and later-phase clinical trials across multiple cancer indications, including as a potential backbone therapy in combination with approved myeloma therapies (STOMP), in liposarcoma (SEAL) and in endometrial cancer (SIENDO), among others. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or currently planned, including multiple studies in combination with approved therapies in a variety of tumor types to further inform Karyopharm’s clinical development priorities for selinexor. Additional clinical trial information for selinexor is available at www.clinicaltrials.gov.
For more information about Karyopharm’s products or clinical trials, please contact the Medical Information department at:
Tel: +1 (888) 209-9326
Email: medicalinformation@karyopharm.com
For additional product information, including full prescribing information, please visit www.XPOVIO.com.
About Karyopharm Therapeutics
Karyopharm Therapeutics Inc. (Nasdaq: KPTI) is a commercial-stage pharmaceutical company pioneering novel cancer therapies and dedicated to the discovery, development, and commercialization of novel first-in-class drugs directed against nuclear export and related targets for the treatment of cancer and other major diseases. Karyopharm’s Selective Inhibitor of Nuclear Export (SINE) compounds function by binding with and inhibiting the nuclear export protein XPO1 (or CRM1). Karyopharm’s lead compound, XPOVIO® (selinexor), is approved in the U.S. in multiple hematologic malignancy indications, including in combination with Velcade® (bortezomib) and dexamethasone for the treatment of patients with multiple myeloma after at least one prior therapy, in combination with dexamethasone for the treatment of patients with heavily pretreated multiple myeloma and as a monotherapy for the treatment of patients with relapsed or refractory diffuse large B-cell lymphoma. A Marketing Authorization Application for NEXPOVIO™ (selinexor) for patients with heavily pretreated multiple myeloma is also currently under review by the European Medicines Agency. In addition to single-agent and combination activity against a variety of human cancers, SINE compounds have also shown biological activity in models of neurodegeneration, inflammation, autoimmune disease, certain viruses and wound-healing. Karyopharm has several investigational programs in clinical or preclinical development. For more information, please visit www.karyopharm.com.
References
1 World Health Organization. 2020. https://gco.iarc.fr/today/data/factsheets/cancers/35-Multiple-myeloma-fact-sheet.pdf
SOURCE: Karyopharm Therapeutics
Post Views: 625
