If approved, Inrebic will become the first new therapy for myelofibrosis in Europe in nearly a decade

Inrebic, if approved, will also be the first once-daily, oral therapy to demonstrate clinically meaningful spleen and symptom response for patients with myelofibrosis where treatment with ruxolitinib has failed or who are JAK inhibitor naïve

PRINCETON, NJ, USA I December 11, 2020 I Bristol Myers Squibb (NYSE: BMY) today announced the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended approval of 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. The CHMP recommendation will now be reviewed by the European Commission (EC), which has the authority to approve medicines for the European Union (EU). If approved, Inrebic will be the first, once-daily oral therapy to significantly reduce spleen volume and symptom burden for patients with myelofibrosis where treatment with ruxolitinib has failed or who are JAK inhibitor naïve.

The CHMP adopted a positive opinion based on results from the JAKARTA and JAKARTA2 studies. 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.1 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.2

“For nearly a decade, patients with myelofibrosis who have progressed on ruxolitinib have had no treatment options for this rare bone marrow disorder, characterized by debilitating symptoms and an enlarged spleen,” said Diane McDowell, M.D., vice president, Hematology Global Medical Affairs, Bristol Myers Squibb. “The positive CHMP opinion for Inrebic reinforces our commitment to improving on standards of care for patients living with hard-to-treat blood diseases and we look forward to the European Commission’s decision.”

The EC is expected to deliver its final decision within 67 days of receipt of the CHMP opinion. The decision will be applicable to all EU member states and Iceland, Norway and Liechtenstein.

Inrebic is approved in the United States for the treatment of adult patients with intermediate-2 or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis.1 In Canada, Inrebic is approved for the treatment of splenomegaly and/or disease related symptoms in adult patients with intermediate-2 or high-risk primary myelofibrosis, post-polycythemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis, including patients who have been previously exposed to 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.

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)1 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.2

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. 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).1,2

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

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.

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References:

  1. INREBIC U.S. Prescribing Information. Accessed November 2020.
  2. 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 November 2020.
  3. INREBIC Canada Product Monograph. Accessed November 2020.
  4. Mayo Clinic. Myelofibrosis. Available at: https://www.mayoclinic.org/diseases-conditions/myelofibrosis/symptomscauses/syc-20355057. Accessed November 2020.
  5. Leukemia & Lymphoma Society. Myelofibrosis. Available at: https://www.lls.org/myeloproliferativeneoplasms/myelofibrosis. Accessed November 2020.
  6. Moulard O, et al. Epidemiology of myelofibrosis, essential thrombocythemia, and polycythemia vera in the European Union. European Journal of Haematology. 2013;92:289/297.
  7. 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.
  8. Abdel-Wahab O and Levine R. Primary myelofibrosis: Updates on Definition, Pathogenesis and Treatment. Annual Review of Medicine. 2009;60:233-245.
  9. Mesa R, Niblack J, Wadleigh M, et al. The burden of fatigue and quality of life in myeloproliferative disorders (MPDs). Cancer. 2007;109:68-76.

SOURCE: Bristol Myers Squibb