The U.S. Food and Drug Administration today approved Aimovig
(erenumab-aooe) for the preventive treatment of migraine in adults. The
treatment is given by once-monthly self-injections. Aimovig is the first
FDA-approved preventive migraine treatment in a new class of drugs that work by
blocking the activity of calcitonin gene-related peptide, a molecule that is
involved in migraine attacks.
"Aimovig provides patients with a novel option for
reducing the number of days with migraine," said Eric Bastings, M.D.,
deputy director of the Division of Neurology Products in the FDA's Center for
Drug Evaluation and Research. "We need new treatments for this painful and
often debilitating condition."
Patients often describe migraine headache pain as an intense
pulsing or throbbing pain in one area of the head. Additional symptoms include
nausea and/or vomiting and sensitivity to light and sound. Approximately
one-third of affected individuals can predict the onset of a migraine because
it is preceded by an aura – transient sensory or visual disturbances that
appear as flashing lights, zig-zag lines or a temporary loss of vision. People
with migraine tend to have recurring attacks triggered by a number of different
factors, including stress, hormonal changes, bright or flashing lights, lack of
food or sleep and diet. Migraine is three times more common in women than in
men and affects more than 10 percent of people worldwide.
The effectiveness of Aimovig for the preventive treatment of
migraine was evaluated in three clinical trials. The first study included 955
participants with a history of episodic migraine and compared Aimovig to
placebo. Over the course of six months, Aimovig-treated patients experienced,
on average, one to two fewer monthly migraine days than those on placebo. The
second study included 577 patients with a history of episodic migraine and
compared Aimovig to placebo. Over the course of three months, Aimovig-treated
patients experienced, on average, one fewer migraine day per month than those
on placebo. The third study evaluated 667 patients with a history of chronic
migraine and compared Aimovig to placebo. In that study, over the course of
three months, patients treated with Aimovig experienced, on average, 2 ½ fewer
monthly migraine days than those receiving placebo.
The most common side effects that patients in the clinical
trials reported were injection site reactions and constipation.
The FDA granted the approval of Aimovig to Amgen Inc.
https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm608120.htm
https://www.doximity.com/doc_news/v2/entries/12372713
My migraines started slow: They were infrequent but very
severe in my late 20s and early 30s. After I had chemotherapy and radiation for
colon cancer treatment, they became so much more severe. The radiation therapy
put me into early menopause. At that point, they became so frequent that I was
taking about 12 migraine abortive pills every month.
They would knock the headache back, but even a tamped-down
migraine is not so much fun. It’s an all-body thing. It’s not just nausea; it’s
a mental stupidity of a really shocking nature. It makes you super slow, like
you’re trying to swim through molasses. Everything ordinary is just very, very
hard. I was also very sensitive to light. You really just want to put a blanket
over your head and lock yourself in a dark room.
It was affecting my attendance at work. I would go in late
and I would be propped up at my desk. It’s so sad to think of all the things
that I missed — all the times I had to call in sick, and all the fun things I
missed. I missed Bruce Springsteen at Fenway Park because I had a migraine. I
heard it was really good!
I tried pretty much everything to prevent migraines —
antidepressants, blood pressure pills, anti-seizure pills — some of which had
pretty nasty side effects. I had to stop drinking alcohol for over 10 years,
because every time I drank it would trigger a headache. I tried eliminating all
kinds of things: chocolate, cheeses, Diet Coke, milk. Not enough sleep can give
you a headache. Travel can give you a headache, because it combines stress and
not enough sleep. It’s really, really hard to control those kinds of factors.
No matter what I did, I would get a headache.
I had started subscribing to the National Headache
Foundation newsletters, and they sent me an email about this clinical trial. I
thought, “Gosh, I have nothing to lose.” So I signed up. That was almost four
years ago, and I haven’t had a migraine in over a year.
Once they doubled the dose of the shot, which they did
midway through the study, that was when the headaches went to zero. I had zero
side effects, which has really been remarkable, especially considering all the
preventive things I tried and the side effects that they have. I haven’t
renewed my prescription for that abortive headache medication in a year. I used
to carry those things in my purse, and I had one in my suitcase. I was always
ready in case a headache would strike. Now I’m just skipping around.
http://time.com/5282661/aimovig-migraine-treatment/
https://www.doximity.com/doc_news/v2/entries/12372713
Dodick DW, Ashina M, Brandes JL, Kudrow D, Lanteri-Minet M, Osipova V, Palmer K, Picard H, Mikol DD, Lenz RA. ARISE: A Phase 3 randomized trial of erenumab for episodic migraine. Cephalalgia. 2018 May;38(6):1026-1037.
ReplyDeleteAbstract
Background Calcitonin gene-related peptide plays an important role in migraine pathophysiology. Erenumab, a human monoclonal antibody that inhibits the calcitonin gene-related peptide receptor, is being evaluated for migraine prevention. Methods In this randomized, double-blind, placebo-controlled, phase 3 study, 577 adults with episodic migraine were randomized to placebo or 70 mg erenumab; 570 patients were included in efficacy analyses. Primary endpoint was change in monthly migraine days. Secondary endpoints were ≥50% reduction in monthly migraine days, change in acute migraine-specific medication treatment days, and ≥5-point reduction in Physical Impairment and Impact on Everyday Activities domain scores measured by the Migraine Physical Function Impact Diary. All endpoints assessed change from baseline at month 3. Results Patients receiving erenumab experienced -2.9 days change in monthly migraine days, compared with -1.8 days for placebo, least-squares mean (95% CI) treatment difference of -1.0 (-1.6, -0.5) ( p < 0.001). A ≥ 50% reduction in monthly migraine days was achieved by 39.7% (erenumab) and 29.5% (placebo) of patients (OR:1.59 (95% CI: 1.12, 2.27) ( p = 0.010). Migraine-specific medication treatment days were reduced by -1.2 (erenumab) and -0.6 (placebo) days, a treatment difference of -0.6 (-1.0, -0.2) ( p = 0.002). The ≥5-point reduction rates in Migraine Physical Function Impact Diary - Physical Impairment were 33.0% and 27.1% (OR:1.33 (0.92, 1.90) ( p = 0.13) and in Migraine Physical Function Impact Diary - Everyday Activities were 40.4% and 35.8% (OR:1.22 (0.87, 1.71) ( p = 0.26). Safety and adverse event profiles of erenumab were similar to placebo. Most frequent adverse events were upper respiratory tract infection, injection site pain, and nasopharyngitis. Conclusions As a preventive treatment of episodic migraine, erenumab at a dosage of 70 mg monthly significantly reduced migraine frequency and acute migraine-specific medication use. (Funded by Amgen). Trial registration ClinicalTrials.gov, NCT02483585.
Goadsby PJ, Reuter U, Hallström Y, Broessner G, Bonner JH, Zhang F, Sapra S, Picard H, Mikol DD, Lenz RA. A Controlled Trial of Erenumab for Episodic Migraine. N Engl J Med. 2017 Nov 30;377(22):2123-2132.
ReplyDeleteAbstract
BACKGROUND:
We tested erenumab, a fully human monoclonal antibody that inhibits the calcitonin gene-related peptide receptor, for the prevention of episodic migraine.
METHODS:
We randomly assigned patients to receive a subcutaneous injection of either erenumab, at a dose of 70 mg or 140 mg, or placebo monthly for 6 months. The primary end point was the change from baseline to months 4 through 6 in the mean number of migraine days per month. Secondary end points were a 50% or greater reduction in mean migraine days per month, change in the number of days of use of acute migraine-specific medication, and change in scores on the physical-impairment and everyday-activities domains of the Migraine Physical Function Impact Diary (scale transformed to 0 to 100, with higher scores representing greater migraine burden on functioning).
RESULTS:
A total of 955 patients underwent randomization: 317 were assigned to the 70-mg erenumab group, 319 to the 140-mg erenumab group, and 319 to the placebo group. The mean number of migraine days per month at baseline was 8.3 in the overall population; by months 4 through 6, the number of days was reduced by 3.2 in the 70-mg erenumab group and by 3.7 in the 140-mg erenumab group, as compared with 1.8 days in the placebo group (P<0.001 for each dose vs. placebo). A 50% or greater reduction in the mean number of migraine days per month was achieved for 43.3% of patients in the 70-mg erenumab group and 50.0% of patients in the 140-mg erenumab group, as compared with 26.6% in the placebo group (P<0.001 for each dose vs. placebo), and the number of days of use of acute migraine-specific medication was reduced by 1.1 days in the 70-mg erenumab group and by 1.6 days in the 140-mg erenumab group, as compared with 0.2 days in the placebo group (P<0.001 for each dose vs. placebo). Physical-impairment scores improved by 4.2 and 4.8 points in the 70-mg and 140-mg erenumab groups, respectively, as compared with 2.4 points in the placebo group (P<0.001 for each dose vs. placebo), and everyday-activities scores improved by 5.5 and 5.9 points in the 70-mg and 140-mg erenumab groups, respectively, as compared with 3.3 points in the placebo group (P<0.001 for each dose vs. placebo). The rates of adverse events were similar between erenumab and placebo.
CONCLUSIONS:
Erenumab administered subcutaneously at a monthly dose of 70 mg or 140 mg significantly reduced migraine frequency, the effects of migraines on daily activities, and the use of acute migraine-specific medication over a period of 6 months. The long-term safety and durability of the effect of erenumab require further study. (Funded by Amgen and Novartis; STRIVE ClinicalTrials.gov number, NCT02456740 .).
de Hoon J, Van Hecken A, Vandermeulen C, Yan L, Smith B, Chen JS, Bautista E, Hamilton L, Waksman J, Vu T, Vargas G. Phase I, Randomized, Double-blind, Placebo-controlled, Single-dose, and Multiple-dose Studies of Erenumab in Healthy Subjects and Patients With Migraine. Clin Pharmacol Ther. 2018 May;103(5):815-825.
ReplyDeleteAbstract
Monoclonal antibodies (mAbs) targeting calcitonin gene-related peptide (CGRP) signaling are being explored as prophylactic treatments for migraine. Erenumab (AMG 334) is the first potent, selective, and competitive human mAb antagonist of the CGRP receptor. We report the data from two phase I studies assessing the safety, pharmacokinetics (PK), and pharmacodynamics of single and multiple administrations of erenumab in healthy subjects and patients with migraine. The results indicate that the PK profile of erenumab is nonlinear from 1 mg to 70 mg and the linear portion of the clearance from 70 mg to 210 mg is consistent with other human immunoglobulin G2 antibodies. Single doses of erenumab resulted in >75% inhibition of capsaicin-induced dermal blood flow, with no apparent dose-dependency for erenumab ≥21 mg. Erenumab was generally well tolerated, with an acceptable safety profile, supporting further clinical development of erenumab for migraine prevention.