Novartis announces new positive data showing AMG 334 significantly reduces monthly migraine days in chronic migraine vs placebo
Sep 15, 2016
Detailed results from Phase II study in chronic migraine prevention showed patients on AMG 334 (erenumab) were significantly more likely to experience a 50% or more reduction in monthly migraine days compared to placebo
Chronic migraine is the most disabling form of the disease, and is associated with substantial personal pain and disability, and financial cost to society 1,2
AMG 334 is being co-developed by Novartis and Amgen for the prevention of migraine
Frimley September 15, 2016 – Novartis today announced detailed Phase II results showing the fully human monoclonal antibody AMG 334 (erenumab) demonstrated a statistically significant reduction in monthly migraine days compared with placebo in patients with chronic migraine (CM).3 Significantly more patients receiving monthly subcutaneous AMG 334 70mg or 140mg experienced a 50% or more reduction in the number of monthly migraine days compared with placebo (40%, 41% and 23%, respectively).3 The data were presented at the 5th European Headache and Migraine Trust International Congress (EHMTIC) in Glasgow, Scotland.
“This is an exciting time in the treatment of chronic migraine, which has a profound impact on the lives of those who suffer from the disease,” said Vasant Narasimhan, Global Head, Drug Development and Chief Medical Officer for Novartis. “These important data further support the efficacy of AMG 334 in patients who currently have limited therapeutic options. We are committed to continuing our work in migraine to provide a potential new treatment to patients suffering from this debilitating disease.”
The study included 667 patients who had a mean baseline of approximately 18 migraine days per month, and were randomised to receive either subcutaneous placebo or subcutaneous AMG 334 70mg or 140mg once a month.4 Across both doses, patients observed a statistically significant 6.6-day reduction from baseline in monthly migraine days compared with 4.2 days observed in those on placebo (p<0.001).3 A reduction of 50% or more in number of monthly migraine days was observed in 40% and 41% (70mg and 140mg doses, respectively) of individuals in the AMG 334 groups, representing a significantly higher likelihood of response compared to 24% of those receiving placebo (both p<0.001).3 All endpoint assessments compared the last four weeks of the 12-week treatment phase to baseline.4
Other key secondary endpoints results from the Phase II CM study are:
Reductions in monthly acute migraine-specific medication days (i.e. the number of days where patients took a migraine-specific medication in a month) were 3.5 days and 4.1 days in the 70mg and 140mg groups, respectively, representing statistically significant reductions compared to a 1.6-day reduction in those receiving placebo (both p<0.001).3
All groups showed numeric improvements in cumulative monthly headache hours. Compared to a 55.22-hour reduction vs. baseline in the placebo group, reductions were 64.76 hours for 70mg AMG 334 and 74.53 hours for 140 mg AMG 334.3
In an analysis of exploratory endpoints, both doses of AMG 334 were associated with significant improvements in health-related quality of life, headache impact, disability, and pain interference outcome measurements, compared to placebo.*5
The safety profile of AMG 334 was similar to placebo across both treatment arms.3 No specific adverse event was reported in greater than 5% of patients treated with AMG 334. The most common adverse events (in placebo, 70 mg AMG 334 and 140mg AMG 334 groups, respectively) were injection site pain (1.1%, 3.7% and 3.7%), upper respiratory tract infection (1.4%, 2.6% and 3.2%) and nausea (2.5%, 2.1% and 3.2%).3
Migraine is the most prevalent of all neurological disorders, with more than 10% of the worldwide population affected.1 It profoundly limits patients' abilities to carry out everyday tasks and as such, the World Health Organization has declared migraine to be one of the top ten causes of disability for men and women.1,6 CM is characterised by at least 15 headache days per month, of which eight or more days have migraine features, for more than three months.7,8 It is the most debilitating form of migraine, and it is challenging for healthcare professionals to treat. As such, CM patients experience a substantial negative impact on daily activities and quality of life.9
Results from phase III studies investigating AMG 334 in episodic migraine are expected later this year. AMG 334 is being co-developed by Amgen and Novartis. As part of the collaboration, Amgen retained commercialisation rights in the U.S., Canada and Japan, and Novartis has rights in Europe and rest of world.
* Assessment tools for exploratory endpoints included the Headache Impact Test (HIT-6™), Migraine Disability Assessment (MIDAS), Migraine-Specific Quality-of-Life Questionnaire (MSQ), and the Patient Reported Outcome Measurement Information System (PROMIS®) Pain Interference Scale Short Form. Exploratory endpoints were not adjusted for multiple comparisons.
About the Phase II Chronic Migraine Study The Phase II chronic migraine study is a global phase II, randomised, 12-week, double-blind, placebo-controlled study evaluating the efficacy and safety of AMG 334 in chronic migraine prevention.4 In the study, 667 patients were randomised to receive once-monthly subcutaneous placebo or AMG 334 (70mg or 140mg) in a 3:2:2 ratio respectively.4 The primary outcome measure was the change in monthly migraine days from baseline to the last four weeks of the 12-week treatment phase in patients with chronic migraine (the number of migraine days between weeks nine and 12).4 Secondary study endpoints included achievement of at least a 50% reduction from baseline in monthly migraine days in the last four weeks of the 12-week treatment phase (50% responder rate), acute migraine-specific medication use days, and change from baseline in cumulative monthly headache hours.4 Exploratory endpoints included health-related quality of life, headache impact, disability, and pain interference outcome measurements.4
About Migraine Migraine involves recurrent attacks of incapacitating head pain that is typically pulsating, often unilateral and associated with nausea, vomiting and sensitivity to light, sound and odours.10 Migraine is associated with personal pain, disability and reduced quality of life, and financial cost to society.2 It remains under-recognised and under-treated with more than 40% of people going undiagnosed.2,11 Chronic migraine is characterised by at least 15 headache days per month, of which eight or more days have migraine features, for more than three months.7.8
About AMG 334 AMG 334 is a fully human monoclonal antibody being investigated for the prevention of migraine. AMG 334 binds to the Calcitonin-Gene-Related-Peptide (CGRP) receptor, thereby inhibiting its activation by CGRP. Through its receptor, CGRP is thought to be pivotal in the genesis of migraine.12 AMG 334 is currently being studied in a number of large global, randomised, double-blind, placebo-controlled trials to assess its safety and efficacy in migraine prevention.
About the Amgen and Novartis Neuroscience Collaboration In August 2015, Novartis entered into a global collaboration with Amgen to jointly develop and commercialise pioneering neuroscience treatments in the field of Alzheimer's Disease (AD) and migraine. The companies are partnering in the development and commercialisation of a beta-secretase 1 (BACE) inhibitor programme in AD with Novartis' oral therapy CNP520 (currently in a phase II study for AD).
About Novartis in Neuroscience Novartis has a strong ongoing commitment to neuroscience (NS) and to bringing innovative treatments to patients suffering from neurological conditions where there is a high unmet need. We currently offer patients and physicians a large drug portfolio encompassing Multiple Sclerosis (MS), Alzheimer's disease, Parkinson's disease, Epilepsy and Attention Deficit Hyperactivity Disorder, and have a pipeline in MS, Alzheimer's disease, migraine and specialty neurology (e.g. neuropathic pain).
References: 1. National Institute of Neurological Disorders and Stroke. NINDS Migraine Information. What is Migraine? http://www.ninds.nih.gov/disorders/migraine/migraine.html. (Link is external) Accessed August 2016. 2. World Health Organization. Headache disorders. http://www.who.int/mediacentre/factsheets/fs277/en/. Accessed August 2016. 3. Tepper S et al. Phase II, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Erenumab (AMG 334) in Chronic Migraine Prevention. Poster presented at: 5th European Headache and Migraine Trust Annual Congress; September 15-18, 2016; Glasgow, UK. 4. ClinicalTrials.gov A study to evaluate the Efficacy and Safety of AMG 334 in Chronic Migraine Prevention. https://clinicaltrials.gov/ct2/show/NCT02066415?term=20120295&rank=1(Link is external) Accessed August 2016. 5. Tepper S et al. Patient Reported Outcomes in Chronic Migraine Patients Receiving Placebo or Erenumab (AMG 334) in a Phase II Randomized, Double-Blind Study. Poster presented at: 5th European Headache and Migraine Trust Annual Congress; September 15-18, 2016; Glasgow, UK. 6. Vos T et al. Global Burden of Disease Study. Lancet. 2015; 386(9995):743–800. 7. Headache Classification Subcommittee of the International Headache Society. Cephalalgia 2013; 33:629–808 8. International Headache Society. The International Classification of Headache Disorders. http://ihs-classification.org/en/02_klassifikation/02_teil1/01.05.01_migraine.html (link is external) Accessed August 2016 9. Katsarava, Z. et al. Defining the differences between episodic migraine and chronic migraine. Curr Pain Headache Rep 2012; 16:86-92. 10. National Institute for Neurological Disorders and Stroke. Headache: Hope Through Research. http://www.ninds.nih.gov/disorders/headache/detail_headache.htm (link is external). Accessed August 2016. 11. Diamond S et al. Patterns of Diagnosis and Acute and Preventive Treatment for Migraine in the United States: Results from the American Migraine Prevalence and Prevention Study. Headache. 2007; 47(3):355-63 12. Hansen JM et al. Calcitonin gene-related peptide triggers migraine-like attacks in patients with migraine with aura. Cephalalgia. 2010; 30(10):1179-86.
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