Originally published in Pharmafile

The numbers are staggering. Over one billion people worldwide, making it the world’s third most prevalent disease. 1 It is the second leading global cause of years lived with disability and the leading cause in those under the age of 50. 2 One in four US households are affected. 157 million workdays are lost annually in the US alone. 1 $78 billion annual cost in the US3 and €111 billion annual cost in the EU.4 Hearing the magnitude of impact of this disease, how many people would guess that I am speaking about migraine? Why isn’t there more widespread discussion on this burden and heightened awareness of the impact? Why aren’t healthcare professionals regularly screening patients for this common, disabling disease? Why have patients traditionally had few efficacious and tolerable treatments, and why have they faced stigma, including the perception that migraine is “just a headache”?

Throughout the eight years I was a practicing neurologist with a subspecialty certification in Headache Medicine, I witnessed firsthand the devastation that migraine and other headache disorders could cause. While I had tools available to try and help patients treat attacks when they occurred (known as acute treatments) and others to help them prevent their attacks (known as preventive treatments), those tools often provided insufficient efficacy, engendered tolerability concerns, and largely lacked an indication for migraine or other headache disorders. Patients would take a preventive medication for months, praying that it would reduce their frequency of attacks and disability, but many would call in tears, still suffering from crippling attacks or addled by adverse drug reactions that they felt did not justify their level of improvement. Challenged by their inadequate treatment experiences, I found that patients were often discontinuing preventive medications, consistent with studies showing that up to 80 percent of patients discontinue oral migraine preventive medications within six months.5 I became increasingly frustrated by the lack of any drug development for the preventive treatment of migraine and became determined to chart a new course in my career where I could help find solutions to these problems.

Fortune was on my side as I discovered an opportunity at Teva Pharmaceuticals as a Medical Director in the Migraine & Headache Therapeutic Area. While it was clear from my interview that Teva was committed to leadership in migraine and headache, the depth of this commitment to improving the lives of those afflicted with these diseases became much more evident after I joined the company. Not only was Teva rapidly advancing its development program in migraine for fremanezumab (then called TEV-48125), a humanized monoclonal antibody that binds to calcitonin gene-related peptide (CGRP) ligand and blocks its binding to the receptor, but clinical development programmes were also underway to address debilitating headache disorders for which nothing else was indicated, including cluster headache and post-traumatic headache.

Having witnessed firsthand the patients with the greatest unmet need in this therapeutic area, I was dedicated to working with my Teva colleagues to identify ways to best help these patients. In addition to studying fremanezumab in the overall migraine population and demonstrating efficacy in the preventive treatment of migraine, we also worked to uncover its benefits in patients suffering from difficult-to-treat migraine. Migraine management may be complicated by any of the following:

  • Comorbidities: Migraine is known to be comorbid with many diseases, including chronic pain,6 IBS,7 depression, and anxiety.6 Presence of one or more comorbidities often leads to poorer outcomes, increased disability, reduced quality of life, and treatment challenges as management of one disease may trigger worsening of the other.8
  • Medication overuse: Frequent use of acute treatments for migraine may exacerbate the disease and lead to increased frequency of attacks and may precipitate new onset chronic migraine. Management of medication overuse has traditionally involved withdrawal from the inciting medications which is often extremely painful and may elicit withdrawal symptoms.9
  • Prior treatment failures: Patients whose migraine has not responded to prior preventive medications tend to have higher disease burden, greater disability, and fewer available treatment options than those who are treatment naïve.10 

Although these factors that may contribute to more difficult-to-treat migraine have been described in migraine literature for decades, few studies have examined treatment strategies to address them. Until recently, there were no randomised, placebo-controlled trials to study the impact of preventive therapies complicated by one of these three challenging clinical scenarios. Given our commitment to addressing the burden of migraine patients, our Teva team sought to understand the potential benefit of fremanezumab in each of these subgroups of patients with difficult-to-treat migraine.

Ultimately, we’ve seen efficacy of fremanezumab in difficult-to-treat patient populations such as patients with migraine and comorbid moderate to severe depression, those with medication overuse, and those with documented failure to up to four migraine preventive medication classes. 10,11,12,13,14

I am also encouraged by the progress that has been made in migraine care as a whole, such as the introduction, by Industry, of a number of anti-CGRP therapies. However, it is important to remember that there are challenges within the migraine community outside of treatment gaps. Migraine is an underfunded disease, and the burden of migraine and other headache disorders are often not well understood by most governments, policymakers, health authorities and wider society. Combine those elements with the fact that migraine is often stigmatised as being “just a headache”, and it is clear that widespread awareness and patient advocacy in this disease state is needed, and the burden that migraine patients and their loved ones face needs to be better understood.

Teva has shown its dedication to the migraine community through support initiatives such as our sponsorship of the American Registry for Migraine Research, with the goal of enabling research that may allow us to better understand migraine and other headache disorders. Additionally, Teva is a sponsor of the Global Patient Advocacy Coalition, supporting that organisation in its aims to advance a unified global headache advocacy strategy that helps to implement optimal standards of migraine care and raise awareness of its impact on the individual and society. Teva’s support of Move Against Migraine, a campaign dedicated to increasing awareness of migraine and empowering the migraine community in the United States, reinforced Teva’s goal to help patients advocate for themselves and connect with others in the community. Additionally, Teva is proud to recently support the European Migraine and Headache Alliance (EMHA) #LightToMigraine initiative, which aims to strengthen the voice of the global migraine community.

Teva is committed to empowering the migraine community around the world through their health journey by providing online tools based on human insights. In 2018, we launched Life Effects, an online initiative in collaboration with patients, for patients, that provides information, insight and inspiration about the reality of living with chronic diseases such as migraine. The website consists of articles, videos and podcasts that examine the long-term effects and the impact migraine has on a patient’s broader day-to-day life. We have also partnered with Healint, the developer of the Migraine Buddy© tracking app, and the Migraine Trust International Symposium (MTIS) to create independent, trustworthy and reliable online health information.

Teva has shown its dedication to the migraine community is through its support of the documentary Out of My Head. This documentary, by Eleventh Hour Films, was created by a filmmaker whose daughter suffered from crippling migraine attacks with the goal of exploring and educating on migraine and why it is so misunderstood worldwide. Teva embraced the opportunity to increase awareness of migraine and help more treating physicians understand the often misunderstood patient impact that this devastating disease has on millions worldwide. To accomplish this, the documentary needed to get in front of key stakeholders and thus Teva sponsored screenings of the documentary at medical congresses worldwide.

Partnering with key opinion leaders, we are examining other critical areas of unmet need within migraine, as well as within the entirety of Headache Medicine overall, to ensure we generate data to inform the treatment of patients most in need of clinical solutions. For example, we have recently launched UNITE, a randomised, double-blind, placebo-controlled clinical trial in patients with migraine and comorbid major depressive disorder to better understand the efficacy and safety of fremanezumab in this patient population given that an estimated 40 percent of people with migraine have comorbid depression.15 

Additionally, to further support migraine and headache research, Teva provides grants to support independent investigator sponsored research, and provides unrestricted educational grants to help improve understanding and awareness of migraine and other headache disorders. As we continue to create the highest quality data possible to inform clinical management of migraine and other headache diseases, as well as actively support the migraine community through a wide range of initiatives, Teva hopes we can provide better days for those afflicted by these disabling diseases.

References

  1. Migraine Research Foundation. About Migraine Facts. https://migraineresearchfoundation.org/about-migraine/migraine-facts/. Accessed October 2019.
  2. Global, regional, and national burden of migraine and tension-type headache, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol 2018;17:954-76.
  3. Gooch CL, Pracht E, Borenstein AR. The burden of neurological disease in the United States: A summary report and call to action. Ann Neurol 2017;81:479-484.
  4. Linde M, Gustavsson A, Stovner LJ, et al. The cost of headache disorders in Europe: the Eurolight project. Eur J Neurol 2012;19(5):703-11.
  5. Hepp Z, Bloudek LM, Varon SF. Systematic Review of Migraine Prophylaxis Adherence and Persistence. J Manag Care Pharm 2014;20(1):22-33.
  6. Bigal ME. The Epidemiology, Burden, and Comorbidities of Migraine. Neurologic Clinics 2009;27(2):321-334.
  7. Mulak A, Paradowski L. Migraine and irritable bowel syndrome. Neurol Neurochir Pol 2005;39(4 Suppl 1):S55-60.
  8. Buse DC, Manack A, Serrano D, et al. Sociodemographic and comorbidity profiles of chronic migraine and episodic migraine sufferers. Journal of Neurology, Neurosurgery & Psychiatry 2010;81:428-432.
  9. American Migraine Foundation. Medication Overuse Headache. https://americanmigrainefoundation.org/resource-library/medication-overuse-headache-2/ Accessed October 2019.
  10. Ferrari MD, Diener HC, Ning X, et al. Fremanezumab versus placebo for migraine prevention in patients with documented failure to up to four migraine preventive medication classes (FOCUS): a randomised, double-blind, placebo-controlled, phase 3b trial. The Lancet 2019;394(10203):1030-1040.
  11. Cohen JM, et al. Efficacy of Fremanezumab on Migraine Frequency and Depression in Patients with Chronic Migraine and Comorbid Moderate to Moderately Severe Depression. 2018. The American Headache Society Annual Meeting.
  12. Silberstein SD, Ashina S, Katsarava Z, et al. The Impact of Fremanezumab on Medication Overuse in Patients with Chronic Migraine. Presented at the 12th European Headache Federation (EHF) Congress; September 28-30, 2018; Florence, Italy.
  13. Lipton RB, Cohen JM, Ramirez-Campos V, et al. Efficacy with Fremanezumab in Migraine Patients with Comorbid Moderate to Severe Depression and Documented Inadequate Responses to 2-4 Classes of Migraine Preventive Treatments: Subgroup Analysis of the Randomized, Placebo-controlled FOCUS Study. Presented at the International Headache Congress (IHC); September 5-8, 2019; Dublin, Ireland. 
  14. Silberstein S, Cohen J, Ramirez-Campos V, et al. Efficacy of Fremanezumab in Migraine Patients With Medication Overuse and Documented Inadequate Response to 2-4 Classes of Migraine Preventive Treatments: Subgroup Analysis of the Randomized, Placebo-Controlled FOCUS Study. Presented at the International Headache Congress (IHC); September 5-8, 2019; Dublin, Ireland. 
  15. Anxiety and Depression Association of America. Headaches. https://adaa.org/understanding-anxiety/related-illnesses/headaches. Accessed October 2019.  

Date of Preparation: December 2019
UK/CPE/18/0019(1)h