Perspective on the Rx Pipeline - The Pros and Cons of the Calcitonin Gene-Related Peptide (CGRP) Inhibitors Class
Calcitonin Gene-Related Peptide (CGRP) Inhibitors
Migraines are a common disorder that can be debilitating and have a severe negative impact on a patient’s quality of life and productivity. A 2015 article by the American Headache Society (AHS) reported that migraines and severe headaches affect about 14% of adults in the United States. The same article also referenced that headaches were the fourth leading cause of emergency department visits in 2009-2010.
Another recent study concluded that migraine treatment contributes over $9 billion a year to healthcare expenditures. However, preventative medications for chronic migraine have remained an unmet need. This is because none of the commonly used treatments were researched and developed specifically for migraines, consisting of beta blockers (e.g., metoprolol and propranolol), antidepressants (e.g., amitriptyline and venlafaxine), and anti-seizure medications (e.g., valproate and topiramate). These can be effective at preventing migraine attacks, with 50% of patients experiencing a 50% reduction in migraine episodes; however, the high doses required often lead to intolerable adverse events requiring the medication to be discontinued.
Migraine therapy is about to change though, with a new class of medications being developed known as calcitonin gene-related peptide (CGRP) inhibitors. Inhibiting the calcitonin gene-related peptide pathway represents a novel and targeted approach to chronic migraine prevention. Early clinical trial data has shown some promise in decreasing the amount of migraine days a patient may experience and is cause for cautious anticipation.
Due to the ineffectiveness of existing migraine preventative therapies and the number of patients affected by chronic migraines, there is potential for high utilization of CGRP inhibitors. While not priced astronomically high (estimated at $8,000–$14,000 per year), as compared to recent approved therapies for other diseases, the new treatment could attract a large number of migraine sufferers, and plan sponsors could see a significant financial impact. Alternatively, preventing migraines from occurring can greatly improve quality of life and may decrease overall expenditures on other healthcare costs (e.g., emergency room visits, primary care visits and medications prescribed to treat a migraine attack).
Efficacy and Dosing of CGRP Inhibitors: Phase II clinical trials have demonstrated that the CGRP inhibitors can decrease the number of days that a patient experiences a migraine by one to two days versus placebo. The CGRP inhibitors have shown that 50% of patients responded to therapy with a 50% reduction in migraine days per month, while only 30% of patients responded in the placebo group. A recently released analysis of a phase II clinical trial for erenumab concluded that the efficacy in patients who have failed two or more previous therapies may be enhanced. In phase III clinical trials (not published to date), early data suggests that some patients are achieving 75% and 100% reduction in migraine episodes.
Overall, the available data suggests that CGRP inhibitors are well tolerated, safe and have a low incidence of serious adverse events. Nasopharyngitis (nasal swelling), respiratory tract infections, nausea and fatigue were reported as the most common side effects in phase II clinical trials.
There will potentially be various dosage forms available for this class of medications. The products scheduled to be reviewed by the FDA first are subcutaneous and intravenous injections. These formulations are dosed once a month with the possibility of every three month dosing for one of the products; however, this is still being investigated. Oral formulations of CGRP inhibitors may also be available in the future, but are currently in earlier stages of development.
Impact to the Pharmacy Care Experience
The impact of the CGRP inhibitors on the migraine prevention landscape is yet to be determined. The need for medications that safely and effectively prevent or reduce the number of migraine episodes and the subsequent negative impact to quality of life, is great. Early clinical trial data suggests that medications that target the CGRP pathway may play an important role in the future of chronic migraine management.
As these products have yet to be approved by the FDA, EnvisionRx will continue to monitor the research pipeline and, as data becomes available, will provide more insight to the clinical management of these potentially impactful medications.
Payer Action Plan
Stay Informed: As CGRP inhibitors have not yet been approved by the FDA, there is no immediate action for plan sponsors. However, with the number of migraine sufferers and the potentially positive impact this class of medications could bring, payers should stay informed to determine the best course of action for plan management.
 Burch, R. C., Loder, S., Loder, E. and Smitherman, T. A. (2015). The Prevalence and Burden of Migraine and Severe Headache in the United States: Updated Statistics From Government Health Surveillance Studies. Headache: The Journal of Head and Face Pain, 55: 21–34. doi:10.1111/head.12482.
 Raval AD; Shah A. (2017). National Trends in Direct Health Care Expenditures among US Adults with Migraine: 2004 to 2013. J Pain. 2017; 18(1):96-107.
 Goadsby PJ, Lipton RB, Ferrari MD. (2002). Migraine—Current Understanding and Treatment. N Engl J Med 2002; 346:257.
Our Clinical Steering Committee
The Envision Clinical Steering Committee brings together leaders across our national pharmacy care company to monitor the drug landscape, provide recommendations on how to address changes, and to ensure our clients and patients are prepared—in advance.
With any new development, we partner with our Pharmacy & Therapeutics (P&T) Committee and consult with our best-in-class specialty pharmacy, to provide a balanced perspective on the clinical effectiveness of all available options, the cost impact to our plan sponsors and patients, and the impact on the overall patient experience.
Kel Riley, MD
Chief Medical Officer