New preventative migraine drug erenumab (Aimovig) approved by FDA

17.5.2018. On May 17, 2018, the US Food and Drug Administration (FDA) approved Aimovig (erenumab-AOOE) for the preventative treatment of migraine in adults. Treatment is carried out by self-injecting the drug under the skin once a month. Aimovig is the first FDA-approved migraine preventive medication in a new class of migraine prevention medications. They work by inhibiting the activity of calcitonin gene-related peptide (CGRP). The molecule is involved in the development of migraine attacks. “Aimovig provides migraine sufferers with a new option to reduce the number of migraine days per month. “We need new treatments for this painful and often disabling disease,” said Erik Bastings, division director of neurological products at the US Food and Drug Administration.

Migraines occur in over 45 different subtypes. The most common form is migraine without aura. The headaches last 4-72 hours. The headache character is pulsating and throbbing. Physical activity increases the pain, so patients have to stay in bed. The pain attacks are accompanied by nausea and vomiting as well as hypersensitivity to noise and light. Approximately 10-30% of patients experience accompanying neurological symptoms, so-called auras, before the headache phase. Most commonly, visual disturbances occur with zigzag lines that gradually spread across the visual field and disrupt vision. Other symptoms include difficulty finding words, tingling sensations, paralysis and impaired consciousness. Complications of migraine include migraine stroke or epileptic seizures triggered by migraine attacks. Migraines occur approximately three times more often in women than in men. Approximately 10-14% of the population is affected within a year. Approximately 1-2% of the population suffers from chronic migraines. Headache attacks occur on more than 15 days a month.

The effectiveness of Aimovig for the preventive treatment of migraines was evaluated in 3 clinical studies. The first study included 955 participants and analyzed the effect of the drug in the treatment of preventing episodic migraines and compared the effect of Aimovig with that of a drug-free drug (placebo). Over a 6-month period, patients treated with Aimovig experienced an average of 1-2 fewer migraine days per month compared to patients treated with placebo. A second study examined 577 patients with episodic migraine and analyzed the effectiveness of Aimovig and placebo. Over a period of over 3 months, patients treated with Aimovig experienced an average of one day fewer migraines compared to patients treated with placebo. A third study examined 667 patients with chronic migraine and compared the effect of Aimovig with that of placebo. In this study, which lasted 3 months, patients treated with Aimovig experienced an average of 2.5 fewer migraine days per month compared to patients who received placebo. The most commonly observed side effects were pain at the injection site, upper respiratory tract infection and nausea.

“The new drug opens a new era in the treatment of migraines. The approval is good news for patients suffering from the most severe forms of these headaches. It is the first medicine specifically developed for the prevention of episodic and chronic migraines. It specifically intervenes in the mechanisms of migraine development. This inhibits the inflammatory processes that are responsible for migraine headaches. In contrast to all other preventative medications available to date, the new immunotherapy has been developed specifically for migraine prevention for the first time. A slow dosage increase due to intolerances and side effects is not necessary. The onset of effect can be expected quickly within a few days; with conventional preventive medications, this is often only achieved after weeks or even months. Side effects of previous migraine preventatives such as weight gain, mood changes, fatigue, reduced drive or drowsiness do not occur. In contrast to previous medications, which are often discontinued after a short period of time due to such side effects, the treated patients stick with this therapy principle for the long term due to its tolerability and effectiveness. The data available so far shows that one should not assume that the new immunotherapy will stop migraines and that one can live as one wants. On average, the number of headache days is reduced by around 1-3 days per month. On average, the effectiveness is similar to that of previous preventive medications. Particular advantages are the rapid onset of action, the tolerability and the response of patients who could not achieve any effect with other treatments,” comments Prof. Dr. Hartmut Göbel, chief physician at the Kiel Pain Clinic, the new approval.

The new drug is expected to be available in the United States within the next week. The new drug has so far only been studied over relatively short periods of time. The side effects were no more common than those of placebo treatment. However, possible long-term side effects from using the drug for migraines that last years and decades are still open.

Approximately 2% of the population worldwide suffers from chronic migraines. Migraine is classified by the World Health Organization as the third most common disease worldwide and is one of the most common widespread diseases. Headaches are the third most severely disabling human illness. The preventive medications currently available have not been specifically developed for migraine treatment. The preventive effect of these drugs was recognized as a secondary aspect and their effectiveness was then examined in clinical studies. Their effect is limited, but at the same time numerous undesirable side effects occur. As a result, more than 80% of the treated patients discontinue the respective drug after just 1 year, either due to lack of effectiveness or side effects. Over the years, the available medications are tried out one by one or combined. Some patients find the side effects of currently available medications more pronounced than the migraine itself. Due to the unpredictability of attacks, many migraine sufferers are unable to make plans or make commitments and appointments. They are also unable to engage in professional activities. Migraines are likely to be accompanied by psychological complications such as anxiety disorders, depression and personality changes. The risk of high blood pressure, heart attack and stroke is also significantly increased. Severe migraine attacks can occur even in children. Recent studies show that the frequency of migraines in children has risen sharply in recent decades.

Monthly therapy costs in the United States are said to be around $570. The new drug is expected to be available in Europe in the second half of the year. The exact approval text and the definition for which patients the new drug will be reimbursed by health insurance companies are not yet known.

The new class of drugs is based on research efforts spanning over 30 years. In the 1980s, it was discovered that CGRP plays an important role in migraines. CGRP is a neurotransmitter that is important in signal transmission in the nervous system and also plays an important role in vascular control, especially vasodilation. CGRP antibodies block the effect and can thus prevent the mechanisms that cause migraine attacks. Partial blocking of CGRP can prevent migraine attacks without disrupting the normal functioning of the nervous system. The direct development of drugs with the aim of blocking CGRP was initially unsuccessful because it did not show sufficient long-term tolerability. As a result, antibodies were developed that act against the cell surface of the CGRP molecule and inhibit the function of CGRP. The half-life of the antibodies is more than 4 weeks. Therefore, treatment can be carried out every month and the effect of the drug can be maintained in the long term. It is a form of immunotherapy in the sense of a passive vaccination by providing the antibodies from outside. Since the antibodies are not produced in the body themselves, they must be given again every 4 weeks. Drug developments are also underway in which the drug is given through an infusion in the doctor's office every 3 months.

Even if the new drug opens up new options for those affected, it should not be expected that the migraine problem will be solved and that you can live as you want. Knowledge, information, behavior adjustment and regular daily planning are crucial for the prevention and treatment of migraines. Migraine is a complex disease that requires a comprehensive treatment concept, similar to the treatment of diabetes, high blood pressure or asthma. Treatment with medication only plays a partial role. The analysis of the study results shows that the new drug class does not have a sufficient effect in around 50% of the treated patients. In the other patients, the number of migraine days per month is reduced by approx. 1-3 days. A complex treatment concept that includes behavior, knowledge, life adjustment, acute therapy and drug therapy is therefore required.

Summary of the EMA recommendation on erenumab
US product information