We’ve seen major biopharmaceutical discoveries in areas like oncology, cardiovascular disease, diabetes, and liver disease, but treatments for central nervous system (CNS) disorders have been largely stagnant for many years.
In the last few years alone, with breakthrough research and a deeper understanding of neurobiology, some pharmaceutical companies have re-focused their efforts to develop novel treatments to address the significant unmet need in CNS. Migraine is one area of neurology that is seeing promising breakthroughs and these new treatments may help millions of sufferers.
Migraines: physically and emotionally painful
In the U.S., 38 million people suffer from migraines, affecting three times more women than men. Marked by extreme, throbbing headaches, sensitivity to light, sound, and smell, vision changes, aura, and nausea and vomiting, migraines not only impact the simple tasks of daily life, but also create a significant burden on families and the workplace. One study estimates the loss of productivity in the U.S. to be between $5.6 billion to $17.2 billion per year because of missed work.
People who suffer with migraines often don’t seek treatment or they mistakenly believe their migraines are just another headache. As a result, more than 50 percent go undiagnosed. For those who are identified, many are still undertreated.
“Many don’t truly recognize that migraine is a complex neurological disorder that affects millions of people. Despite its prevalence and burden, it has remained an area in need of more options for patients,” said Dr. Charles Hugh-Jones, Chief Medical Officer at Allergan. “Not everyone will respond to the same treatment or experience migraine in the same way.”
Studies have shown that just like mental health conditions, migraines carry a stigma. In fact, a June 2013 study in the journal PLOS One found that chronic migraine sufferers experience the same amount of stigma as people with epilepsy. The stigma can be experienced externally such as in the workplace, as well as internally, which can manifest as fears of lost productivity or reactions from others, for example.
Renewed enthusiasm in research and development of migraine treatments is evident
After the widespread success in the 1990s of drugs like Xanax and Lexapro for people with depression and anxiety, the biopharma industry largely turned its attention away from neuroscience and accelerated R&D efforts into other therapeutic areas.
A report by the Office of Health Economics found the shift has been due in part to neuroscience being the most expensive therapeutic area in addition to low success rates and high development times. There is also a limited understanding of the underlying mechanisms of action for diseases of the brain, and clinical trials often have a high placebo response rate due to the subjective nature of assessment criteria.
“There is no doubt that the brain is complex beyond its own understanding, so it is a very challenging therapeutic area to study. Some companies have even gone so far as to pull out of CNS drug development for that reason,” said Dr. David Nicholson, Ph.D., Chief R&D officer at Allergan. “However, we have definitely seen more interest in the last few years with the research and development of the calcitonin gene-related peptide (CGRP) class.”
While many of the challenges still exist within CNS research, scientific progress has been made in understanding the important role of CGRP and its receptor in the pathophysiology of migraine. The emerging science has given some biopharmaceutical companies a renewed vigor to develop new therapies to prevent migraines and to treat the acute onset — and bring treatment options to the millions who suffer.
In fact, a market review published this year estimates the global migraine market is primed to see dramatic growth to $11 billion by the year 2027 — the prophylaxis market could nearly quadruple to $7 billion and the acute part of the market could more than double to more than $4 billion.
For Allergan, developing treatments for CNS disorders, specifically in migraine, has been a key focus for decades. BOTOX® (onabotulinumtoxinA) has an extensive history of helping patients with a number of therapeutic conditions — the largest of which is chronic migraine. In 2010 it became the first FDA-approved, preventive treatment for adult chronic migraine patients (15 or more headache days a month with headache lasting 4 or more hours each day) and it remains a leader in the migraine space today.
Allergan is also advancing its migraine program with two investigational small molecule oral CGRP treatments, which are being studied for the acute treatment and prevention of migraine. The company has reported positive data on ubrogepant for the acute treatment of migraine and atogepant for migraine prevention. While these are investigational products and, by definition the FDA has not stated an opinion or made any determination on the profile of either drug, the company expects to launch the drugs in 2020 and 2021, respectively.
“Innovation drives everything we do at Allergan,” said Nicholson. “We have been studying migraine treatment for decades and are committed to addressing unmet needs through product innovation for patients who are hopeful for new options that may make a difference in their daily lives.”
BOTOX® (onabotulinumtoxinA) Important Information
BOTOX® is a prescription medicine that is injected to prevent headaches in adults with chronic migraine who have 15 or more days each month with headache lasting 4 or more hours each day in people 18 years or older. It is not known whether BOTOX® is safe or effective to prevent headaches in patients with migraine who have 14 or fewer headache days each month (episodic migraine).
IMPORTANT SAFETY INFORMATION
BOTOX® may cause serious side effects that can be life threatening. Get medical help right away if you have any of these problems any time (hours to weeks) after injection of BOTOX®:
- Problems swallowing, speaking, or breathing, due to weakening of associated muscles, can be severe and result in loss of life. You are at highest risk if these problems are pre-existing before injection. Swallowing problems may last for several months.
- Spread of toxin effects. The effect of botulinum toxin may affect areas away from the injection site and cause serious symptoms including: loss of strength and all-over muscle weakness, double vision, blurred vision and drooping eyelids, hoarseness or change or loss of voice, trouble saying words clearly,loss of bladder control, trouble breathing, trouble swallowing.
There has not been a confirmed serious case of spread of toxin effect away from the injection site when BOTOX® has been used at the recommended dose to treat chronic migraine.
BOTOX® may cause loss of strength or general muscle weakness, vision problems, or dizziness within hours to weeks of taking BOTOX®. If this happens, do not drive a car, operate machinery, or do other dangerous activities.
Do not receive BOTOX® if you: are allergic to any of its ingredients (see Medication Guide for ingredients); had an allergic reaction to any other botulinum toxin product such as Myobloc® (rimabotulinumtoxinB), Dysport® (abobotulinumtoxinA), or Xeomin® (incobotulinumtoxinA); have a skin infection at the planned injection site.
The dose of BOTOX® is not the same as, or comparable to, another botulinum toxin product.
Serious and/or immediate allergic reactions have been reported, including itching, rash, red itchy welts, wheezing, asthma symptoms, or dizziness or feeling faint. Get medical help right away if you experience symptoms; further injection of BOTOX® should be discontinued.
Tell your doctor about all your muscle or nerve conditions such as ALS or Lou Gehrig’s disease, myasthenia gravis, or Lambert-Eaton syndrome, as you may be at increased risk of serious side effects including difficulty swallowing and difficulty breathing from typical doses of BOTOX®.
Tell your doctor about all your medical conditions, including if you: have or have had bleeding problems; have plans to have surgery; had surgery on your face; weakness of forehead muscles; trouble raising your eyebrows; drooping eyelids; any other abnormal facial change; are pregnant or plan to become pregnant (it is not known if BOTOX® can harm your unborn baby); are breastfeeding or plan to (it is not known if BOTOX® passes into breast milk).
Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Using BOTOX® with certain medicines may cause serious side effects. Do not start any new medicines until you have told your doctor that you received BOTOX® in the past.
Tell your doctor if you received any other botulinum toxin product in the last 4 months; have received injections of botulinum toxin such as Myobloc®, Dysport®, or Xeomin® in the past (tell your doctor exactly which product you received); have recently received an antibiotic injection; take muscle relaxants; take allergy or cold medicines; take sleep medicine; take aspirin-like products or blood thinners.
Other side effects of BOTOX® include: dry mouth, discomfort or pain at injection site, tiredness, headache, neck pain, eye problems: double vision, blurred vision, decreased eyesight, drooping eyelids, swelling of eyelids, dry eyes; and drooping eyebrows.
For more information refer to the Medication Guide or talk with your doctor. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.