Aimovig (Erenumab-aooe) David Platero Pamela Gonzales Humberto Colunga

Background on Migraines Migraines are the 3rd most prevalent illness in the world. Migraines are a neurological disorder that is characterized by the expansion of blood vessels in the brain due to the release of inflammatory substances from nerves. The two types of migraines are called migraines with aura and migraines without aura Migraines with aura are subjective sensations (sensitivity to lights or odors, blurred vision, numbness, difficulty speaking, and confusion) that happens before the onset of the migraine. Migraines without aura are more common, and do not have the same subjective sensations before the migraine. Research suggest that migraines may have a genetic component to them. Key stimuli that trigger migraines include: stress, anxiety, loud noises, strong smells, and bright or flashing lights. Recent studies have shown that migraines are often misdiagnosed or treated with narcotics (not an FDA approved treatment for migraine).

Statistics of Migraines in the United States Migraines affect approximately 39 million men, women, and children in the U.S. 18% of women, 6% of men, and 10% of children experience migraines. Before puberty, boys are affected by migraines more than girls. However, during adolescence, the risk of migraines rises for girls. Migraines often go undiagnosed in school-aged children. The healthcare and lost productivity costs that are associated with migraines are estimated to be as high as $36 billion annually. Employers in the U.S. lose more than $13 billion each year due to roughly 113 million lost work days due to migraines. In 2018, there was an estimate 500 certified headache specialists in the U.S. and 39 million “sufferers”.

Mechanism of Action for Migraines

Calcitonin gene-related peptide (CGRP) CGRP is a peptide derived from calcitonin It is produced in both peripheral and central neurons. CGRP is thought to play a role in cardiovascular homeostasis and nociception (response to pain). CGRP is also a vasodilator and can function in the transmission of nociception, causing enhanced synaptic transmission and thereby pain and altered sensory perception.

CGRP plays a key role in migraine pathogenesis Elevated CGRP levels have been reported in serum and saliva during both spontaneous and nitric oxide (NO)-induced migraine attacks. An elevation in serum CGRP levels has also been reported between attacks for both episodic and chronic migraine. In an experiment, an intravenous injection of CGRP caused moderate to severe headaches, which meet the criteria for experimentally induced migraine.

Background on Aimovig Aimovig (Erenumab-aooe) is a human immunoglobulin G2 (IgG2) monoclonal antibody that has a high affinity binding to the CGRP receptor. It is a medication targeted for adults. Medication has not been tested on people under the age of 18. In 2015 Amgen Inc. initiated the collaboration with Novartis Pharmaceuticals Corporation to develop treatments for migraines and Alzheimer's. Aimovig began to be developed in 2018 by Amgen Inc. Active ingredients are: Erenumab-aooe Inactive ingredients include: acetate, polysorbate 80, and sucrose It is marketed by Amgen Inc. and Novartis Pharmaceuticals Corp. Aimovig is a novel therapeutic approach because it was the first FDA-approved treatment specifically developed to prevent migraines by blocking the CGRP receptor. Aimovig has been studied in several large global, randomized, double-blind, placebo-controlled studies to assess its efficacy and safety in migraine prevention.

Mechanism of Action for Aimovig

Studies to Show Efficacy One of the clinical trials used to prove the efficacy of Aimovig looked at how the medicine changed the number of migraines people had in a month. They compared these results with a placebo to make sure that the medicine was actually working as intended. They had 955 participants who were randomly assigned to having an injection of 70 mg of erenumab-aooe, 140 mg of erenumab-aooe, or a placebo every month for six months. The study concluded that erenumab-aooe had a significant reduction of migraine frequency in a month. The average, baseline number of headaches (before experiment) for these people was 8.3 At the end of the six months, the group who received a 70 mg injection had 5.1 migraines/month The group who received 140 mg injections had 4.6 migraines/month The group who received the placebo had 6.5 migraines/month

Aimovig Efficacy The Capsaicin-Induced Dermal Blood Flow test was used to characterize the pharmacokinetics and quantify the inhibitory effects of Aimovig. The method of this experiment involved topical application of Capsaicin to induce local release of CGRP and increase dermal blood flow. The “in vitro” data showed that CGRP-Blocking mAb binds to the the receptor with a relatively high affinity. Dissociation equilibrium constant; KD= 20 pM and a potency measures at IC= 2.3nM in a competitive and reversible manner. Subjects were enrolled in a sequential dose escalation study to determine the optimal dose and most effective route of administration. Erenumab shows maximum target engagement after single and repeated dosing, and has a long serum effective half-life at doses ≥70 mg

How to Take Remove Aimovig box from fridge and let sit at room temperature for 30 minutes. Remove the white cap from autoinjector pen. Stretch or pinch the injection site to create a firm surface (recommend the stomach or thigh). Hold the pen 90° from the skin and firmly push down. Press the purple start cap. Hold down for at least 15 seconds.

Side Effects/Dosage Common Side Effects: Serious Side Effects: Pain, redness, or swelling at injection site Constipation Muscle spasms or cramps Serious Side Effects: An allergic reaction within hours or days of receiving Aimovig Swelling of the mouth, face, tongue, or throat Trouble breathing The recommended dosage for Aimovig is a 70 mg injected subcutaneously once a month. Some patients require a 140 mg dose. Store in box inside a fridge (at 36° to 46°) until use. May be at room temperature up to seven days before use.

Cost of Aimovig US list price for 70 mg or 140 mg once-a-month injections cost $575. An annual cost of $6,900 Cash price, no insurance If it’s covered by insurance, it can still be a very pricy medication. Amgen sponsors an Aimovig Copay Program which allows qualifying patients to receive the medication for $5 for 12 months Only for people with insurance that already covers the medication to some degree Amgen is still working with insurance companies to get the medication more widely covered

Alternate Migraine Medication NSAIDs (non-steroidal anti-inflammatory drugs) Ex. ibuprofen, naproxen, diclofenac Works by decreasing the synthesis of the prostaglandins, which can be involved in migraine formation Can be found over-the-counter Typically a cheap medication Does not work as well as other migraine medication -Triptans Ex. Sumatriptan, Naratriptan, Rizatriptan Works by stimulating serotonin to reduce inflammation and constrict blood vessels in the brain in order to stop the migraine Requires a prescription from a doctor, but can be costly Covered by insurances, but often only a limited quantity per month These medications have been used widely for many years, but they are not preventative. Aimovig’s main appeal is to decrease the likelihood of having a migraine, rather than just treating the symptoms.

Reception of Drug Since this medicine has only been on the market since 2018, there is not a lot of research available for it Aimovig has been portrayed by media as a miracle drug that can help people with migraines far more than any other medicine on the market. However, people who have taken Aimovig have mentioned side effects that they experienced which hindered their ability to use the medication. While some have taken it and had a huge improvement with little to no side effects … Others have complained of side effects that weren’t listed by the FDA: worsening migraines, nausea, vomiting, and an acquired tolerance to other migraine medications Disclaimer: these comments have been pulled from a forum dedicated to people’s experiences of taking the medication. There has not yet been more scholarly sources dealing with the topic. So while it can be very beneficial to some, it’s can cause some serious side effects that haven’t really been widely discussed or studied.

Conclusion Migraines afflict more people than is recognized by the general public. Amgen and Novartis partnered in 2015 to create a medication to better treat the illness. Aimovig was approved in 2018 as a new medication that is meant to prevent migraine formation by binding with the CGRP receptors. This prevents the CGRP from binding to the receptors, which have been linked to migraine formation. Because of how recently it was approved for use in the USA, there is not as much data on it. Side effects and long term effects are under further research. While it can be very helpful for some, it is not a perfect treatment for migraines.

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