Novartis Pharmaceuticals Canada Inc. (Novartis) has received approval from Health Canada for PrJAKAVI® (ruxolitinib tablets), a drug for the treatment of disease-related splenomegaly (enlarged spleen) and/or its associated symptoms in adult patients with myelofibrosis (MF), a blood cancer.[i]
PrJAKAVI® is the first and only JAK 1 and JAK 2 inhibitor approved by Health Canada for the treatment of splenomegaly (enlarged spleen) and/or its associated symptoms in adult patients with MF.[ii] Until now, there were no Health Canada approved treatments for these patients.
About Myelofibrosis
MF develops when uncontrolled signalling in the JAK (“Janus kinase”) pathway – which regulates blood cell production – causes scarring in the bone marrow and faulty blood cell production.[iii],[iv],[v],[vi] This results in an enlarged spleen and other severe complications such as fatigue, fever, night sweats, itchy skin, bone or muscle pain, abdominal pain/discomfort, and weight loss.[vii],[viii] The disease is associated with a significantly reduced quality of life and shortened survival.[ix],[x]
Use of traditional oral therapies for MF aim to reduce spleen volume, relieve symptoms and decrease the risk of complications;[xi],[xii],[xiii] however, these therapies provide limited efficacy and are associated with significant side effects such as leukemic transformation, neuropathy, and depression.
PrJAKAVI® offers a unique mechanism of action that targets what studies suggest is the underlying pathology of the disease, rather than using medications developed for treatment of other conditions that have limited effectiveness.[xiv] A potent and selective dual oral JAK 1 and JAK 2 inhibitor, PrJAKAVI® is designed to specifically inhibit the biological activity of these JAK enzymes for the treatment of this patient population with MF. Inhibition of JAK enzymes blocks abnormal signalling in the JAK pathway to preserve normal blood cell development in the bone marrow.
Indication
An oral prescription therapy taken twice daily, PrJAKAVI® is indicated for the treatment of splenomegaly (enlarged spleen) and/or its associated symptoms in adult patients with MF.[xv]
PrJAKAVI® is available in three strengths: 5 mg, 15 mg and 20 mg tablets taken orally twice daily. For the dosage and administration of PrJAKAVI®, please refer to the approved PrJAKAVI® Product Monograph dated June 15, 2012.[xvi]
The Comfort Studies
Health Canada’s approval of PrJAKAVI® is based on results from the largest clinical program conducted in MF to-date. COMFORT (COntrolled MyeloFibrosis Study with ORal JAK Inhibitor Therapy),[xvii],[xviii] the largest clinical trial program conducted in MF, involved Canadian centres in Vancouver, London, Toronto, Ottawa, Montreal and St. John’s (NFLD), with a total of 24 patients enrolled.
In the first Phase III trial, results from COMFORT-I show PrJAKAVI® provides statistically significant clinical improvement in patients with MF at just 24 weeks as measured by spleen volume reduction and symptom improvement compared to placebo.[xix] Results were first presented at the 47th American Society of Clinical Oncology (ASCO) annual meeting in June 2011.[xx]
In the second Phase III trial, COMFORT-II, data show PrJAKAVI® provides marked and durable clinical improvement in patients with MF, measured by reduction in spleen volume at 48 weeks and 24 weeks compared to best available therapy.[xxi]
PrJAKAVI® Well-tolerated With Manageable Side Effects
PrJAKAVI® is well-tolerated with manageable and predictable side effects, including reversible thrombocytopenia (an abnormal drop in the number of blood cells involved in forming blood clots), anemia (the condition of having less than the normal number of red blood cells or less than the normal quantity of hemoglobin in the blood) and neutropenia (an abnormally low level of neutrophils in the blood). Neutrophils are white blood cells produced in the bone marrow that ingest bacteria).[xxii],[xxiii],[xxiv],[xxv] The three most frequent non-hematological adverse reactions were bruising (21.3%), dizziness (15.0%) and headache (13.6%).[xxvi]
Hematologic adverse reactions were generally transient and manageable through dose reductions/transfusions, and rarely led to discontinuations.[xxvii] Patients who do discontinue therapy revert to the same symptoms prior to treatment.
Used with Permission from National Public Relations
References:
[i] PrJAKAVI® Canadian approved Product Monograph, dated June 15, 2012.
[ii] PrJAKAVI®Canadian approved Product Monograph, dated June 15, 2012.
[iii] Morgan KJ, Gilliland DG. A role for JAK2 mutations in myeloproliferative diseases. Annu Rev Med. 2008;59:213-222.
[iv] Delhommeau F, Jeziorowska D, Marzac C, Casadevall N. Molecular aspects of myeloproliferative neoplasms. Int J Hematol. 2010;91(2):165-173.
[v] Quintás-Cardama A, Vaddi K, Liu P, et al. Preclinical characterization of the selective JAK1/2 inhibitor INCB018424: therapeutic implications for the treatment of myeloproliferative neoplasms. Blood. 2010;115(15):3109-3117.
[vi] The Leukemia & Lymphoma Society. Idiopathic myelofibrosis. 2007. Available at http://www.lls.org/content/nationalcontent/resourcecenter/freeeducationmaterials/mpd/pdf/idiopathicmyelofibrosis.pdf. Accessed January 20, 2012.
[vii] Mesa RA, Schwager S, Radia D, et al. The Myelofibrosis Symptom Assessment Form (MFSAF): an evidence-based brief inventory to measure quality of life and symptomatic response to treatment in myelofibrosis. Leukemia research. Sep 2009;33(9):1199-1203.
[viii] The Leukemia & Lymphoma Society. Idiopathic myelofibrosis. 2007. Available at http://www.lls.org/content/nationalcontent/resourcecenter/freeeducationmaterials/mpd/pdf/idiopathicmyelofibrosis.pdf. Accessed January 20, 2012.
[ix] Mesa, R.A., et al., The Myelofibrosis Symptom Assessment Form (MFSAF): an evidence-based brief inventory to measure quality of life and symptomatic response to treatment in myelofibrosis. Leuk Res, 2009. 33(9): p. 1199-203.
[x] The Leukemia & Lymphoma Society. Idiopathic myelofibrosis. 2007. Available at http://www.lls.org/content/nationalcontent/resourcecenter/freeeducationmaterials/mpd/pdf/idiopathicmyelofibrosis.pdf. Accessed January 20, 2012.
[xi] The Leukemia & Lymphoma Society. Idiopathic myelofibrosis. 2007. Available at http://www.lls.org/content/nationalcontent/resourcecenter/freeeducationmaterials/mpd/pdf/idiopathicmyelofibrosis.pdf. Accessed January 20, 2012.
[xii] Hellman AJ. Myeloproliferative syndromes: diagnosis and therapeutic options. Pol Arch Med Wewn. 2008;118:756-759.
[xiii] Tefferi A. Allogeneic hematopoietic cell transplantation versus drugs in myelofibrosis: the risk-benefit balancing act. Bone Marrow Transpl. 2010;45(3):419-421.
[xiv] PrJAKAVI® Canadian approved Product Monograph, dated June 15, 2012.
[xv] PrJAKAVI® Canadian approved Product Monograph, dated June 15, 2012.
[xvi] PrJAKAVI® Canadian approved Product Monograph, dated June 15, 2012.
[xvii] Verstovsek S, Mesa RA, Gotlib J, et al. A Double-Blind, Placebo-Controlled Trial of Ruxolitinib for Myelofibrosis. New Eng J Med. 2012: March 1;366:799-807.
[xviii] Harrison C, Kiladjian JJ, Al-Ali HK, et al. JAK Inhibition with Ruxolitinib versus Best Available Therapy for Myelofibrosis. New Eng J Med. 2012: March 1;366:787-98.
[xix] Verstovsek S, Mesa RA, Gotlib J, et al. A Double-Blind, Placebo-Controlled Trial of Ruxolitinib for Myelofibrosis. New Eng J Med. 2012: March 1;366:799-807.
[xx] Verstovsek S, Mesa RA, Gotlib JR, et al. Results of COMFORT-I, a randomized double-blind phase III trial of JAK 1/2 inhibitor INCB18424 (424) versus placebo (PB) for patients with myelofibrosis (MF). J Clin Oncol 29: 2011 (suppl; abstr 6500).
[xxi] Harrison C, Kiladjian JJ, Al-Ali HK, et al. JAK Inhibition with Ruxolitinib versus Best Available Therapy for Myelofibrosis. New Eng J Med. 2012: March 1;366:787-98.
[xxii] Verstovsek S, Mesa RA, Gotlib J, et al. A Double-Blind, Placebo-Controlled Trial of Ruxolitinib for Myelofibrosis. New Eng J Med. 2012: March 1;366:799-807.
[xxiii] Harrison C, Kiladjian JJ, Al-Ali HK, et al. JAK Inhibition with Ruxolitinib versus Best Available Therapy for Myelofibrosis. New Eng J Med. 2012: March 1;366:787-98.
[xxiv] Verstovsek S, Kantarjian H, Mesa RA, et al. Safety and Efficacy of JAK1 & JAK2 Inhibitor, INCB018424, in Myelofibrosis. New Eng J Med. 2010 September 16;363:1117-1127.
[xxv] PrJAKAVI® Canadian approved Product Monograph, dated June 15, 2012.
[xxvi] PrJAKAVI® Canadian approved Product Monograph, dated June 15, 2012.
[xxvii] Verstovsek S, Kantarjian H, Mesa RA, et al. Safety and Efficacy of JAK1 & JAK2 Inhibitor, INCB018424, in Myelofibrosis. New Eng J Med. 2010 September 16;363:1117-1127.
