Inrebic, a once-daily, oral therapy, is the first new treatment option approved in Europe for myelofibrosis in nearly a decade
Inrebic demonstrated clinically meaningful spleen and symptom response in myelofibrosis patients where treatment with ruxolitinib has failed, who are intolerant to ruxolitinib or who are JAK inhibitor naïve, based on results from JAKARTA and JAKARTA2 studies
PRINCETON, NJ, USA I February 08, 2021 IBristol Myers Squibb (NYSE: BMY) today announced that the European Commission (EC) has granted full Marketing Authorization for Inrebic ® (fedratinib) for the treatment of disease-related splenomegaly (enlarged spleen) or symptoms in adult patients with primary myelofibrosis, post-polycythaemia vera myelofibrosis or post-essential thrombocythaemia myelofibrosis, who are Janus Associated Kinase (JAK) inhibitor naïve or have been treated with ruxolitinib. Inrebic is the first, once-daily oral therapy to significantly reduce spleen volume and symptom burden for patients with myelofibrosis where treatment with ruxolitinib has failed, who are intolerant to ruxolitinib or who are JAK inhibitor naïve. The centralized Marketing Authorization approves use of Inrebic in all European Union (EU) member states, as well as Norway, Iceland and Liechtenstein.* Inrebic was granted orphan drug designation in the United States and is also approved in the United States and Canada. 1,2
“Myelofibrosis is a serious and often debilitating bone marrow disorder for which there has only been one approved treatment option for nearly a decade,” said Claire Harrison, M.D., FRCP, FRCPath, JAKARTA and JAKARTA2 study investigator and professor of hematology at Guy’s and St. Thomas’ NHS Foundation Trust, London, United Kingdom. “Inrebic showed clinically meaningful reductions in spleen volume and symptoms in patients who progressed on ruxolitinib or who are JAK inhibitor naïve. Approximately one out of every 100,000 people in the EU will be diagnosed with myelofibrosis each year, and today’s approval provides an important new option for patients who have remained in urgent need of new therapies.”
The EC approval of Inrebic was based on results from the JAKARTA and JAKARTA2 studies, which included patients from 14 countries in the EU. The pivotal JAKARTA study evaluated the efficacy of once-daily oral doses of Inrebic compared with placebo in 289 patients with intermediate-2 or high-risk primary or secondary myelofibrosis with splenomegaly. The JAKARTA2 study evaluated the efficacy of once-daily oral doses of Inrebic in 97 patients with intermediate or high-risk primary or secondary myelofibrosis with splenomegaly previously treated with ruxolitinib.3 In the clinical development program of Inrebic, which included 608 patients, serious and fatal cases of encephalopathy, including Wernicke’s, occurred in Inrebic-treated patients. Serious cases were reported in 1.3% (8/608) of patients treated with Inrebic in clinical trials and 0.16% (1/608) of cases were fatal.1
“With today’s EC approval of Inrebic, patients with myelofibrosis throughout Europe will now have a critical new option for a rare bone marrow disorder that’s seen little progress in several years,” said Diane McDowell, M.D., vice president, Hematology Global Medical Affairs, Bristol Myers Squibb. “We’re committed to improving on standards of care for patients living with hard-to-treat blood diseases and are working collaboratively with European member states to make Inrebic available to patients as quickly as possible.”
*Centralized Marketing Authorization does not include approval in Great Britain (England, Scotland and Wales).
About JAKARTA and JAKARTA2
The Inrebic development program consisted of multiple studies (including JAKARTA and JAKARTA2) in 608 patients who received more than one dose (ranging from 30 mg to 800 mg), of whom 459 had myelofibrosis, including 97 previously treated with ruxolitinib.3 JAKARTA was a pivotal Phase 3, multicenter, randomized, double-blind, placebo-controlled trial evaluating the efficacy of once-daily oral doses of Inrebic compared with placebo in patients with intermediate-2 or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis with splenomegaly and a platelet count of ≥50 x 109/L who were previously untreated with a JAK inhibitor. The study included 289 patients randomized to receive either Inrebic 500 mg (n=97) or 400 mg (n=96) or placebo (n=96) across 94 sites in 24 countries.1 JAKARTA2 was a Phase 2, open-label, single arm study of Inrebic in myelofibrosis patients previously treated with ruxolitinib with a diagnosis of intermediate-1 with symptoms, intermediate-2 or high-risk myelofibrosis, post-polycythemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis with splenomegaly and platelet count ≥50 x 109/L. The study included 97 patients who started Inrebic at 400 mg once daily across 10 countries.3
The primary endpoint of JAKARTA and JAKARTA2 was spleen response rate, defined as the proportion of patients achieving greater than or equal to a 35% reduction from baseline in spleen volume at the end of cycle 6 as measured by magnetic resonance imaging (MRI) or computerized tomography (CT) with a follow-up scan 4 weeks later in the JAKARTA study. Secondary endpoints of the studies included symptom response rate, defined as the proportion of patients with a 50% or greater reduction in Total Symptom Score when assessed from baseline to the end of cycle 6 as measured by the modified Myelofibrosis Symptoms Assessment Form (MFSAF) v2.0 diary2 (night sweats, itching, abdominal discomfort, early satiety, pain under ribs on left side, bone or muscle pain).1,3
About Myelofibrosis
Myelofibrosis is a serious and rare bone marrow disorder that disrupts the body’s normal production of blood cells. Bone marrow is gradually replaced with fibrous scar tissue, which limits the ability of the bone marrow to make blood cells. The disorder can lead to anemia, weakness, fatigue and enlargement of the spleen and liver, among other symptoms.4 Myelofibrosis is classified as a myeloproliferative neoplasm, a group of rare blood cancers that are derived from blood-forming stem cells.5 In the EU, approximately 1 of every 100,000 people will be diagnosed with myelofibrosis each year.6 Both men and women are affected, and while the disease can affect people of all ages, the median age at diagnosis ranges from 60 to 67 years.7,8 Median survival after ruxolitinib discontinuation is generally poor, ranging from 6 months to 2 years, representing a significant need for alternative treatment options.9
About Inrebic
Inrebic® (fedratinib) is an oral kinase inhibitor with activity against wild type and mutationally activated Janus Associated Kinase 2 (JAK2) and FMS-like tyrosine kinase 3 (FLT3). Inrebic is a JAK2-selective inhibitor with higher potency for JAK2 over family members JAK1, JAK3 and TYK2. Abnormal activation of JAK2 is associated with myeloproliferative neoplasms, including myelofibrosis and polycythemia vera. In cell models expressing mutationally active JAK2 or FLT3, Inrebic reduced phosphorylation of signal transducer and activator of transcription (STAT3/5) proteins, inhibited cell proliferation, and induced apoptotic cell death. In mouse models of JAK2V617F-driven myeloproliferative disease, Inrebic blocked phosphorylation of STAT3/5, increased survival and improved disease-associated symptoms, including reduction of white blood cells, hematocrit, splenomegaly and fibrosis.1
U.S. INDICATION
INREBIC® (fedratinib) is indicated for the treatment of adult patients with intermediate-2 or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis (MF).
Please see full Prescribing Information, including Boxed WARNING, and Summary of Product Characteristics for INREBIC.
Bristol Myers Squibb: Creating a Better Future for People with Cancer
Bristol Myers Squibb is inspired by a single vision—transforming patients’ lives through science. The goal of the company’s cancer research is to deliver medicines that offer each patient a better, healthier life and to make cure a possibility. Building on a legacy across a broad range of cancers that have changed survival expectations for many, Bristol Myers Squibb researchers are exploring new frontiers in personalized medicine, and through innovative digital platforms, are turning data into insights that sharpen their focus. Deep scientific expertise, cutting-edge capabilities and discovery platforms enable the company to look at cancer from every angle. Cancer can have a relentless grasp on many parts of a patient’s life, and Bristol Myers Squibb is committed to taking actions to address all aspects of care, from diagnosis to survivorship. Because as a leader in cancer care, Bristol Myers Squibb is working to empower all people with cancer to have a better future.
About Bristol Myers Squibb
Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube, Facebook and Instagram.
Celgene and Juno Therapeutics are wholly owned subsidiaries of Bristol-Myers Squibb Company. In certain countries outside the U.S., due to local laws, Celgene and Juno Therapeutics are referred to as, Celgene, a Bristol Myers Squibb company and Juno Therapeutics, a Bristol Myers Squibb company.
References:
- INREBIC U.S. Prescribing Information. Accessed January 2021.
- INREBIC Canada Product Monograph. Accessed January 2021.
- Clinical Trials.gov. Phase II, Open Label, Single Arm Study of SAR302503 In Myelofibrosis Patients Previously Treated With Ruxolitinib (JAKARTA2). Available at https://clinicaltrials.gov/ct2/show/NCT01523171. Accessed January 2021.
- Mayo Clinic. Myelofibrosis. Available at: https://www.mayoclinic.org/diseases-conditions/myelofibrosis/symptomscauses/syc-20355057. Accessed January 2021.
- Leukemia & Lymphoma Society. Myelofibrosis. Available at: https://www.lls.org/myeloproliferativeneoplasms/myelofibrosis. Accessed January 2021.
- Moulard O, et al. Epidemiology of myelofibrosis, essential thrombocythemia, and polycythemia vera in the European Union. European Journal of Haematology. 2013;92:289/297.
- Mesa RA, Silverstein MN, Jacobsen SJ, et al. Population-based incidence and survival figures in essential thrombocythemia and agnogenic myeloid metaplasia: an Olmsted County Study, 1976-1995. Am J Hematol. 1999;61(1):10-15.
- Abdel-Wahab O and Levine R. Primary myelofibrosis: Updates on Definition, Pathogenesis and Treatment. Annual Review of Medicine. 2009;60:233-245.
- Harrison, C.N., Schaap, N. & Mesa, R.A. Management of myelofibrosis after ruxolitinib failure. Ann Hematol 99, 1177–1191 (2020). https://doi.org/10.1007/s00277-020-04002-9.
SOURCE: Bristol Myers Squibb
Post Views: 329
Inrebic, a once-daily, oral therapy, is the first new treatment option approved in Europe for myelofibrosis in nearly a decade
Inrebic demonstrated clinically meaningful spleen and symptom response in myelofibrosis patients where treatment with ruxolitinib has failed, who are intolerant to ruxolitinib or who are JAK inhibitor naïve, based on results from JAKARTA and JAKARTA2 studies
PRINCETON, NJ, USA I February 08, 2021 IBristol Myers Squibb (NYSE: BMY) today announced that the European Commission (EC) has granted full Marketing Authorization for Inrebic ® (fedratinib) for the treatment of disease-related splenomegaly (enlarged spleen) or symptoms in adult patients with primary myelofibrosis, post-polycythaemia vera myelofibrosis or post-essential thrombocythaemia myelofibrosis, who are Janus Associated Kinase (JAK) inhibitor naïve or have been treated with ruxolitinib. Inrebic is the first, once-daily oral therapy to significantly reduce spleen volume and symptom burden for patients with myelofibrosis where treatment with ruxolitinib has failed, who are intolerant to ruxolitinib or who are JAK inhibitor naïve. The centralized Marketing Authorization approves use of Inrebic in all European Union (EU) member states, as well as Norway, Iceland and Liechtenstein.* Inrebic was granted orphan drug designation in the United States and is also approved in the United States and Canada. 1,2
“Myelofibrosis is a serious and often debilitating bone marrow disorder for which there has only been one approved treatment option for nearly a decade,” said Claire Harrison, M.D., FRCP, FRCPath, JAKARTA and JAKARTA2 study investigator and professor of hematology at Guy’s and St. Thomas’ NHS Foundation Trust, London, United Kingdom. “Inrebic showed clinically meaningful reductions in spleen volume and symptoms in patients who progressed on ruxolitinib or who are JAK inhibitor naïve. Approximately one out of every 100,000 people in the EU will be diagnosed with myelofibrosis each year, and today’s approval provides an important new option for patients who have remained in urgent need of new therapies.”
The EC approval of Inrebic was based on results from the JAKARTA and JAKARTA2 studies, which included patients from 14 countries in the EU. The pivotal JAKARTA study evaluated the efficacy of once-daily oral doses of Inrebic compared with placebo in 289 patients with intermediate-2 or high-risk primary or secondary myelofibrosis with splenomegaly. The JAKARTA2 study evaluated the efficacy of once-daily oral doses of Inrebic in 97 patients with intermediate or high-risk primary or secondary myelofibrosis with splenomegaly previously treated with ruxolitinib.3 In the clinical development program of Inrebic, which included 608 patients, serious and fatal cases of encephalopathy, including Wernicke’s, occurred in Inrebic-treated patients. Serious cases were reported in 1.3% (8/608) of patients treated with Inrebic in clinical trials and 0.16% (1/608) of cases were fatal.1
“With today’s EC approval of Inrebic, patients with myelofibrosis throughout Europe will now have a critical new option for a rare bone marrow disorder that’s seen little progress in several years,” said Diane McDowell, M.D., vice president, Hematology Global Medical Affairs, Bristol Myers Squibb. “We’re committed to improving on standards of care for patients living with hard-to-treat blood diseases and are working collaboratively with European member states to make Inrebic available to patients as quickly as possible.”
*Centralized Marketing Authorization does not include approval in Great Britain (England, Scotland and Wales).
About JAKARTA and JAKARTA2
The Inrebic development program consisted of multiple studies (including JAKARTA and JAKARTA2) in 608 patients who received more than one dose (ranging from 30 mg to 800 mg), of whom 459 had myelofibrosis, including 97 previously treated with ruxolitinib.3 JAKARTA was a pivotal Phase 3, multicenter, randomized, double-blind, placebo-controlled trial evaluating the efficacy of once-daily oral doses of Inrebic compared with placebo in patients with intermediate-2 or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis with splenomegaly and a platelet count of ≥50 x 109/L who were previously untreated with a JAK inhibitor. The study included 289 patients randomized to receive either Inrebic 500 mg (n=97) or 400 mg (n=96) or placebo (n=96) across 94 sites in 24 countries.1 JAKARTA2 was a Phase 2, open-label, single arm study of Inrebic in myelofibrosis patients previously treated with ruxolitinib with a diagnosis of intermediate-1 with symptoms, intermediate-2 or high-risk myelofibrosis, post-polycythemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis with splenomegaly and platelet count ≥50 x 109/L. The study included 97 patients who started Inrebic at 400 mg once daily across 10 countries.3
The primary endpoint of JAKARTA and JAKARTA2 was spleen response rate, defined as the proportion of patients achieving greater than or equal to a 35% reduction from baseline in spleen volume at the end of cycle 6 as measured by magnetic resonance imaging (MRI) or computerized tomography (CT) with a follow-up scan 4 weeks later in the JAKARTA study. Secondary endpoints of the studies included symptom response rate, defined as the proportion of patients with a 50% or greater reduction in Total Symptom Score when assessed from baseline to the end of cycle 6 as measured by the modified Myelofibrosis Symptoms Assessment Form (MFSAF) v2.0 diary2 (night sweats, itching, abdominal discomfort, early satiety, pain under ribs on left side, bone or muscle pain).1,3
About Myelofibrosis
Myelofibrosis is a serious and rare bone marrow disorder that disrupts the body’s normal production of blood cells. Bone marrow is gradually replaced with fibrous scar tissue, which limits the ability of the bone marrow to make blood cells. The disorder can lead to anemia, weakness, fatigue and enlargement of the spleen and liver, among other symptoms.4 Myelofibrosis is classified as a myeloproliferative neoplasm, a group of rare blood cancers that are derived from blood-forming stem cells.5 In the EU, approximately 1 of every 100,000 people will be diagnosed with myelofibrosis each year.6 Both men and women are affected, and while the disease can affect people of all ages, the median age at diagnosis ranges from 60 to 67 years.7,8 Median survival after ruxolitinib discontinuation is generally poor, ranging from 6 months to 2 years, representing a significant need for alternative treatment options.9
About Inrebic
Inrebic® (fedratinib) is an oral kinase inhibitor with activity against wild type and mutationally activated Janus Associated Kinase 2 (JAK2) and FMS-like tyrosine kinase 3 (FLT3). Inrebic is a JAK2-selective inhibitor with higher potency for JAK2 over family members JAK1, JAK3 and TYK2. Abnormal activation of JAK2 is associated with myeloproliferative neoplasms, including myelofibrosis and polycythemia vera. In cell models expressing mutationally active JAK2 or FLT3, Inrebic reduced phosphorylation of signal transducer and activator of transcription (STAT3/5) proteins, inhibited cell proliferation, and induced apoptotic cell death. In mouse models of JAK2V617F-driven myeloproliferative disease, Inrebic blocked phosphorylation of STAT3/5, increased survival and improved disease-associated symptoms, including reduction of white blood cells, hematocrit, splenomegaly and fibrosis.1
U.S. INDICATION
INREBIC® (fedratinib) is indicated for the treatment of adult patients with intermediate-2 or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis (MF).
Please see full Prescribing Information, including Boxed WARNING, and Summary of Product Characteristics for INREBIC.
Bristol Myers Squibb: Creating a Better Future for People with Cancer
Bristol Myers Squibb is inspired by a single vision—transforming patients’ lives through science. The goal of the company’s cancer research is to deliver medicines that offer each patient a better, healthier life and to make cure a possibility. Building on a legacy across a broad range of cancers that have changed survival expectations for many, Bristol Myers Squibb researchers are exploring new frontiers in personalized medicine, and through innovative digital platforms, are turning data into insights that sharpen their focus. Deep scientific expertise, cutting-edge capabilities and discovery platforms enable the company to look at cancer from every angle. Cancer can have a relentless grasp on many parts of a patient’s life, and Bristol Myers Squibb is committed to taking actions to address all aspects of care, from diagnosis to survivorship. Because as a leader in cancer care, Bristol Myers Squibb is working to empower all people with cancer to have a better future.
About Bristol Myers Squibb
Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube, Facebook and Instagram.
Celgene and Juno Therapeutics are wholly owned subsidiaries of Bristol-Myers Squibb Company. In certain countries outside the U.S., due to local laws, Celgene and Juno Therapeutics are referred to as, Celgene, a Bristol Myers Squibb company and Juno Therapeutics, a Bristol Myers Squibb company.
References:
- INREBIC U.S. Prescribing Information. Accessed January 2021.
- INREBIC Canada Product Monograph. Accessed January 2021.
- Clinical Trials.gov. Phase II, Open Label, Single Arm Study of SAR302503 In Myelofibrosis Patients Previously Treated With Ruxolitinib (JAKARTA2). Available at https://clinicaltrials.gov/ct2/show/NCT01523171. Accessed January 2021.
- Mayo Clinic. Myelofibrosis. Available at: https://www.mayoclinic.org/diseases-conditions/myelofibrosis/symptomscauses/syc-20355057. Accessed January 2021.
- Leukemia & Lymphoma Society. Myelofibrosis. Available at: https://www.lls.org/myeloproliferativeneoplasms/myelofibrosis. Accessed January 2021.
- Moulard O, et al. Epidemiology of myelofibrosis, essential thrombocythemia, and polycythemia vera in the European Union. European Journal of Haematology. 2013;92:289/297.
- Mesa RA, Silverstein MN, Jacobsen SJ, et al. Population-based incidence and survival figures in essential thrombocythemia and agnogenic myeloid metaplasia: an Olmsted County Study, 1976-1995. Am J Hematol. 1999;61(1):10-15.
- Abdel-Wahab O and Levine R. Primary myelofibrosis: Updates on Definition, Pathogenesis and Treatment. Annual Review of Medicine. 2009;60:233-245.
- Harrison, C.N., Schaap, N. & Mesa, R.A. Management of myelofibrosis after ruxolitinib failure. Ann Hematol 99, 1177–1191 (2020). https://doi.org/10.1007/s00277-020-04002-9.
SOURCE: Bristol Myers Squibb
Post Views: 329
