Health Canada Approves INREBIC® (fedratinib), First New Treatment in Nearly a Decade for Patients Living with Myelofibrosis

INREBIC^® provides new, once-daily oral option for patients affected by rare bone marrow cancer

MONTREAL, Sept. 21, 2020 /CNW/ - Bristol Myers Squibb Canada (BMS) announced today that Health Canada has approved INREBIC^® (fedratinib), a new once-daily oral medication used to treat adults with an enlarged spleen and associated symptoms caused by intermediate-2 or high-risk primary myelofibrosis, post-polycythemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis.¹

INREBIC^® is the first new treatment for patients with myelofibrosis in nearly a decade to demonstrate a clinically meaningful reduction in spleen volume for patients in the approved population affected by this serious and rare bone marrow cancer.¹ A new treatment provides Canadians living with myelofibrosis, and their caregivers, with more options to find a treatment that works for them.

Myelofibrosis is a serious and rare bone marrow disorder that disrupts the body’s normal production of blood cells.² Bone marrow is gradually replaced with fibrous scar tissue, which limits the ability of the bone marrow to make blood cells.² Currently, there are an estimated 1,400 to 2,177 Canadians who are living with myelofibrosis.³

“The approval of INREBIC^® represents a milestone for the way healthcare practitioners treat this rare disorder, which can have debilitating symptoms,” said Dr. Vikas Gupta, Director, The Elizabeth and Tony Comper MPN Program, Princess Margaret Cancer Centre, Toronto. “Canadians living with myelofibrosis now have a new treatment option that may be better suited to their needs and has shown promise for alleviating the symptom burden associated with myelofibrosis.”

INREBIC^® is a janus kinase (JAK) inhibitor and is the first new treatment for patients with myelofibrosis in nearly a decade.^1,4 JAK proteins send signals that tell the body to make more blood cells, but myelofibrosis makes it difficult for the bone marrow to create normal blood cells, which potentially moves blood cell production to the spleen.¹ However, by blocking the activity of JAK proteins, INREBIC^® can reduce the size of the spleen and improve symptoms.

“As part of our commitment to Canadians living with cancer, we are excited to provide INREBIC^® as a new treatment option for those impacted by myelofibrosis,” said Al Reba, General Manager, Bristol Myers Squibb Canada. “We hope that the option of a once-daily oral treatment will have a positive and meaningful impact on Canadians living with the disease.”

Health Canada’s approval of INREBIC^® included findings from the JAKARTA and JAKARTA2 clinical trials. The JAKARTA study, a double-blind, randomized, placebo-controlled Phase 3 study, involved patients with intermediate-2 or high-risk myelofibrosis, post-polycythemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis. The JAKARTA2 study, a multicenter, open-label, single-arm Phase 2 study, involved patients previously exposed to ruxolitinib with a diagnosis of intermediate-1 with symptoms, intermediate-2 or high-risk primary myelofibrosis, post-polycythemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis.

About Myelofibrosis
Myelofibrosis is classified as a myeloproliferative neoplasm, a group of rare blood cancers that are derived from blood-forming stem cells.² Myelofibrosis can lead to anemia and thrombocytopenia, weakness, fatigue and enlargement of the spleen and liver, among other symptoms.² In Canada, approximately 36 to 360 people will be diagnosed with myelofibrosis each year.³ Both men and women are affected, and while the disease can affect people of all ages, the median age at diagnosis is 69 years old.³

About JAKARTA
JAKARTA was a double-blind, randomized, placebo-controlled Phase 3 study in patients with intermediate-2 or high-risk myelofibrosis (MF), post-polycythemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis with splenomegaly and platelet count ≥50 x 10⁹/L. A total of 289 patients were randomized to receive either INREBIC^® 500 mg (N=97), 400 mg (N=96), or placebo (N=96) once daily for at least 6 cycles. The median age was 65 years (range 27 to 86 years), 47% of patients were older than 65 years, and 59% were male. Sixty-four percent (64%) of patients had primary MF, 26% had post-polycythemia vera MF, and 10% had post-essential thrombocythemia MF. Fifty-two percent (52%) of patients had intermediate-2 risk, and 48% had high-risk disease. The median hemoglobin count at baseline was 10.2 g/dL. The median platelet count at baseline was 213.5 x 10⁹/L; 16.3% of patients had a platelet count <100 x 10⁹/L, and 83.7% of patients had a platelet count ≥100 x 10⁹/L. Patients had a median palpable spleen length of 15 cm at baseline and a median spleen volume as measured by magnetic resonance imaging (MRI) or computed tomography (CT) of 2568 mL (range of 316 to 8244 mL) at baseline. (The median normal spleen volume is approximately 215 mL).¹

The primary efficacy endpoint was the proportion of patients achieving a greater than or equal to 35% reduction from baseline in spleen volume at the End of Cycle 6 as measured by MRI or CT and confirmed 4 weeks later.¹

One of the secondary endpoints was the proportion of patients with a 50% or greater reduction in Total Symptom Score (TSS) from baseline to the End of Cycle 6 as measured by the modified Myelofibrosis Symptoms Assessment Form (MFSAF) v2.0 diary.¹

About JAKARTA2
JAKARTA2 was a multicenter, open-label, single-arm Phase 2 study in patients previously exposed to 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.¹

A total of 97 patients were enrolled and treated with INREBIC^® 400 mg once daily. The median age was 67 years (range 38 to 83 years) with 58% of patients older than 65 years and 55% were male. Fifty-five percent (55%) of patients had primary MF, 26% had post-polycythemia vera MF, and 19% had post-essential thrombocythemia MF. Sixteen percent (16%) of patients had intermediate-1 with symptoms, 49% had intermediate-2, and 35% had high-risk disease. The median hemoglobin count was 9.8 g/dL at baseline. The median platelet count was 147.0 x 10⁹/L at baseline; 34.0% of patients had a platelet count <100 x 10⁹/L, and 66.0% of patients had a platelet count ≥100 x 10⁹/L. Patients had a median palpable spleen length of 18 cm at baseline and a median spleen volume as measured by magnetic resonance imaging (MRI) or computed tomography (CT) of 2893.5 mL (range of 737 to 7815 mL) at baseline.¹

The median duration of prior exposure to ruxolitinib was 10.7 months (range 0.1 to 62.4 months). Seventy-one percent (71%) of patients had received doses of either 30 mg or 40 mg daily of ruxolitinib prior to study entry.¹

The primary endpoint was the subject response rate, defined as the proportion of subjects who have a ≥35% reduction in volume of spleen size at the end of Cycle 6.¹

One of the secondary endpoints was the proportion of patients with a 50% or greater reduction in Total Symptom Score (TSS) from baseline to the End of Cycle 6 as measured by the modified Myelofibrosis Symptoms Assessment Form (MFSAF) diary.¹

About INREBIC^®
INREBIC^® (fedratinib) is indicated 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.

About Bristol Myers Squibb Canada

Bristol Myers Squibb Canada Co. is an indirect wholly-owned subsidiary of Bristol Myers Squibb Company, 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 global operations, visit www.bms.com. Bristol Myers Squibb Canada Co. delivers innovative medicines for serious diseases to Canadian patients in the areas of cardiovascular health, oncology, and immunoscience. Bristol Myers Squibb Canada Co. employs more than 300 people across the country. For more information, please visit www.bmscanada.ca.

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:

1. INREBIC^® Canada Product Monograph. July 10, 2010.
2. Leukemia & Lymphoma Society of Canada. Myelofibrosis. Available at: https://www.llscanada.org/myeloproliferative-neoplasms/myelofibrosis. Accessed July 28, 2020.
3. Corinne S. Hodgson & Associates. Blood Cancer in Canada Facts & Stats 2016. Leukemia & Lymphoma Society of Canada 2016; 4-8.
4. Canadian MPN Group. Myelofibrosis. Available at: http://www.mpncanada.com/about-mpns/practitioner-reference/myelofibrosis/#treatment-options. Accessed July 28, 2020.

SOURCE Bristol Myers Squibb Canada Co.