Analyses of Phase III data provided evidence of sustained spleen
reduction and quality of life improvements
DORVAL, QC, March 7, 2014 /CNW/ - Study results presented at the 55th
American Society of Hematology (ASH) annual meeting showed that
patients with myelofibrosis who received treatment with Jakavi® (ruxolitinib) sustained reductions in spleen volume and sustained
improvements in quality of life after three years of treatment. These
results were demonstrated in analyses from the Phase III COMFORT-I
(COntrolled MyeloFibrosis Study with ORal JAK Inhibitor Therapy) study.
These long-term follow up results build on previously established data
and reinforce the sustained efficacy and long-term safety profile of
Jakavi® in patients with myelofibrosis.
Of the patients treated with Jakavi® 59% experienced at least a 35% reduction in spleen size at any time
during the three year study. In an exploratory analysis, patients who
continued on therapy experienced sustained improvements in the Global
Health Status/Quality of Life and the functional domains of the EORTC
Core Quality of Life questionnaire (EORTC QLQ-C30). Median follow-up
was 149 weeks at the time of the updated analysis.
This scientific data was presented at ASH as new clinical information
regarding Jakavi® and is not contained in the current Canadian approved product monograph.
Jakavi® is indicated for the treatment of splenomegaly and/or its associated
symptoms in adult patients with primary myelofibrosis (also known as
chronic idiopathic myelofibrosis), postpolycythemia vera myelofibrosis
or post-essential thrombocythemia myelofibrosis.1
"The long-term results of the COMFORT-I study provided data supporting
the safety and efficacy of ruxolitinib in myelofibrosis, and the
benefit on quality of life is significant," said Dr. Vikas Gupta a
myeloproliferative neoplasms specialist at the Princess Margaret Cancer
Centre in Toronto. "Several novel agents are on the horizon in the
treatment of myelofibrosis, and we are entering an era of renewed hope
for myelofibrosis patients."
Latest Presented COMFORT Data
The COMFORT-I study is part of the largest clinical trial program in
myelofibrosis to date. Further analyses of phase III data were
presented at the 2013 ASH annual meeting early in December. Jakavi® continues to reduce risk of deaths for patients with myelofibrosis as
reported in the following abstracts:
Impact of Prognostically Detrimental Mutations in COMFORT-II (abstract
Three-Year Update From COMFORT-I Study (abstract #396)3.
A Pooled Overall Survival Analysis of the COMFORT Studies (abstract
A Retrospective Comparison of the DIPSS and COMFORT-II Study (abstract
For full study details please go to: http://www.hematology.org/Meetings/Annual-Meeting/Abstracts/5810.aspx
COMFORT Studies Background
The COMFORT (COntrolled MyeloFibrosis Study with ORal JAK Inhibitor Therapy) studies are randomized, Phase III studies comparing the safety
and efficacy of Jakavi® with placebo or best available treatment (BAT) in patients with
intermediate-2- or high-risk primary myelofibrosis, post-polycythemia
vera myelofibrosis, or post-essential thrombocythemia myelofibrosis.
COMFORT-I is a double-blind study whereas COMFORT-II is open label.
Patients initially received Jakavi® 15 or 20 mg twice daily based on their platelet counts at baseline
(100-200 and > 200 x 109/L, respectively) and were individually titrated to maximize safety and
efficacy. Patients were allowed to cross over from the control arms of
each study upon protocol-defined progression events (primarily
progressive splenomegaly, defined as a ≥ 25% increase in spleen volume
from baseline or on-study nadir in COMFORT-I and -II, respectively). At
the time of the analysis reported at the 2013 American Society of
Hematology annual meeting, all ongoing control patients had crossed
over to Jakavi®. Overall survival was a secondary endpoint in both studies4.
Myelofibrosis is a life-threatening blood cancer with a poor prognosis
and limited treatment options6. Myelofibrosis develops when uncontrolled signaling in the JAK pathway
- which regulates blood cell production - causes the body to make blood
cells that do not work properly, which scars the bone marrow and
results in an enlarged spleen and other severe complications7. Although the exact prevalence is uncertain, a recent analysis done in
the United States estimates myelofibrosis prevalence ranged from
3.6-5.7 per 100,000 patients8. Myelofibrosis is typically diagnosed in people between 50 and 80 years
old, although the disease can arise at any age. Both men and women are
Studies showed that patients with myelofibrosis have a decreased life
expectancy, with a median overall survival of 5.7 years10. Although allogeneic stem cell transplantation may cure myelofibrosis,
the procedure is associated with significant morbidity and
transplant-related mortality, and is available to less than 5% of patients who are young and fit
enough to undergo the procedure11.
About Jakavi® (ruxolitinib)
Jakavi® (ruxolitinib) is an oral inhibitor of the JAK 1 and JAK 2 tyrosine
kinases approved by Health Canada in July 2012 for the treatment of
splenomegaly (enlarged spleen) and/or its associated symptoms in adult
patients with myelofibrosis.
Important Safety Information
Jakavi® can cause serious side effects, including a decrease in blood cell
count and infections. Complete blood count monitoring is recommended.
Dose reduction or interruption may be required in patients with severe
hepatic or renal impairment or in patients developing hematologic
adverse reactions such as thrombocytopenia, anemia and neutropenia.
Dose reductions are also recommended when Jakavi® is co-administered with strong CYP3A4 inhibitors. Patients receiving
Jakavi® should be monitored for pulse rate and blood pressure. Use of Jakavi® during pregnancy is not recommended and women should avoid becoming
pregnant during Jakavi® therapy. Women taking Jakavi® should not breast feed.
The most common adverse drug reactions, occurring at any level of
severity (incidence >10%) are urinary tract infections, anemia,
thrombocytopenia, neutropenia, hypercholesterolemia, dizziness,
headache, alanine aminotransaminase increased, asparte aminotransferase
increased, bruising, bleeding and increased blood pressure. Other
common adverse drug reactions (incidence 1 to 10%) are herpes zoster,
weight gain, flatulence and tuberculosis (1%). In the post-marketing
setting, Progressive multifocal leukencephalopathy (PML) has been
reported. Physicians should be alert for neuropsychiatric symptoms
suggestive of PML1. For additional product information, please refer to the Jakavi® Canadian product monograph.
Novartis Pharmaceuticals Canada Inc., a leader in the healthcare field,
is committed to the discovery, development and marketing of innovative
products to improve the well-being of all Canadians. In 2012, the
company invested close to $100 million in research and development in
Canada. Novartis Pharmaceuticals Canada Inc. employs more than 600
people in Canada. For further information, please consult www.novartis.ca.
Novartis Pharmaceuticals Canada Inc. is a subsidiary of Novartis AG,
which provides innovative healthcare solutions that address the
evolving needs of patients and societies. Headquartered in Basel,
Switzerland, Novartis Group of Companies offers a diversified portfolio
to best meet these needs: innovative medicines, eye care, cost-saving
generic pharmaceuticals, preventive vaccines and diagnostic tools,
over-the-counter and animal health products. Novartis is the only
global company with leading positions in these areas. In 2013, the
Group achieved net sales of USD 57.9 billion, while R&D throughout the
Group amounted to approximately USD 9.9 billion (USD 9.6 billion
excluding impairment and amortization charges). Novartis Group
companies employ approximately 136,000 full-time-equivalent associates
and operate in more than 140 countries around the world.
For more information, please visit http://www.novartis.com.
®Jakavi is a registered trademark
1 Product Monograph, Jakavi (ruxolitinib) Novartis Pharmaceuticals Canada
Inc., revised August 14, 2013. Available at: http://novartis.ca/products/en/pharmaceuticals-j.shtml
2 Guglielmelli P, Biamonte F, Pieri L, et al. Impact of Prognostically
Detrimental Mutations (ASXL1, EZH2, SRSF2, IDH1/2) on Outcomes in
Patients With Myelofibrosis Treated With Ruxolitinib in COMFORT-II.
Abstract #107.55th American Society of Hematology (ASH) Annual Meeting
and Exposition, 2013. New Orleans, LA.
3 Verstovsek S, Ruben M, Gotlib J, et al. Long-Term Outcome of
Ruxolitinib Therapy in Patients with Myelofibrosis: 3-Year Update From
COMFORT-I. Abstract #396. 55th American Society of Hematology (ASH)
Annual Meeting and Exposition, 2013. New Orleans, LA.
4 Vannucchi A, Hagpop K, Kiladjian JJ, et al. A Pooled Overall Survival
Analysis of the COMFORT Studies: 2 Randomized Phase 3 Trials of
Ruxolitinib for the Treatment of Myelofibrosis. Abstract #2820.55th
American Society of Hematology (ASH) Annual Meeting and Exposition,
2013. New Orleans, LA.
5 Passamonti F, Maffioli M, Cervantes F, et al. Impact of Ruxolitinib on
the Natural History of Patients with Primary Myelofibrosis: A
Retrospective Comparison of the DIPSS and the COMFORT-II Cohorts.
Abstract#4066. 55th American Society of Hematology (ASH) Annual Meeting
and Exposition, 2013. New Orleans, LA.
6 Gangat N, Caramazza D, Vaidya R, et al. DIPSS-plus: A refined Dynamic
International Prognostic Scoring System (DIPSS) for primary
myelofibrosis that incorporates prognostic information from karyotype,
platelet count and transfusion status. J Clin Oncol. 2011; 29:392-397.
7 Mesa RA, Schwagera 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.
Leuk Res. 2009;33:1199-1203.
8 MPN Foundation. Prevalence (MF) Available at: http://www.mpnresearchfoundation.org/Prevalence Accessed December 2013
9 Leukemia & Lymphoma Society of Canada. Incidence: Idiopathic
myelofibrosis. Available at: http://www.llscanada.org/#/diseaseinformation/myeloproliferativediseases/incidence/. Accessed December 2013.
10 Cervantes F, Dupriez B, Pereira A, et al. New prognostic scoring system
for primary myeloﬁbrosis based on a study of the International Working
Group for Myeloﬁbrosis Research and Treatment. Blood. 2009;113:2895-2901.
11 Patriarca F, Bacigalupo A, Sperotto A, et al. Allogeneic hematopoietic
stem cell transplantation in myelofibrosis: the 20-year experience of
the Gruppo Italiano Trapianto di Midollo Osseo (GITMO). Haematologica. 2008;93(10):1514-1522.
SOURCE: Novartis Pharmaceuticals Canada Inc.
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