A King’s College London study shows treatment with the drug erenumab cut the number of days with migraine symptoms for 50% of patients.
Across the UK, an estimated 8.5m people live with migraine and research suggests the condition is likely to impact the lives of almost 200,000 people every day. There is an urgent need for new treatment options and erenumab is the first and only fully human monoclonal antibody of its kind designed to specifically prevent migraine. It works by blocking the calcitonin gene-related peptide (CGRP) receptor, which plays a critical role in migraine activation.
Amgen and Novartis, the co-developers of erenumab, funded this Phase III STRIVE study.
‘STRIVE is the first fully reported Phase III study of the CGRP pathway monoclonal antibodies, and it clearly shows that blocking this pathway can reduce the impact of migraine,’ said Peter Goadsby, director, NIHR-Wellcome Trust King’s Clinical Research Facility and professor of neurology at King’s College London. ‘The results of STRIVE represent a real transition for migraine patients from poorly understood, repurposed treatments, to a specific migraine-designed therapy. STRIVE, as with the monoclonal antibody developments generally, represents an incredibly important step forward for migraine understanding and migraine treatment.’
These data show erenumab can significantly reduce the number of monthly migraine days experienced by patients, with a 3.7-day and 3.2-day reduction with erenumab 140 mg and 70 mg, respectively, from a baseline of 8.3-days (1.8-day reduction with placebo). Additionally, 50% of patients treated with erenumab 140 mg had the number of days with migraine symptoms cut by at least half (this figure was 43.3% following treatment with erenumab 70 mg, and 26.6% with placebo). Results from the Migraine Physical Function Impact Diary (MPFID) show patients treated with erenumab also reported improved physical health and ability to participate in daily activities over the six-month trial period. Erenumab has also been shown to be effective and tolerable over the long term with a safety profile comparable to placebo.
“Migraine is too often trivialised as just a headache when, in reality, it can be a debilitating, chronic condition that can destroy lives” said Simon Evans, CEO, Migraine Action. “The effects can last for hours – even days in many cases. An option that can prevent migraine and that is well tolerated is therefore sorely needed and we hope that this marks the start of real change in how this condition is treated and perceived.”
Goadsby is a National Institute for Health Research (NIHR) senior investigator.
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.
Peter J Goadsby, Uwe Reuter, Yngve Hallström, Gregor Broessner, Jo H Bonner, Feng Zhang, Sandhya Sapra, Hernan Picard, Daniel D Mikol, Robert A Lenz
A new study of fremanezumab, an immunotherapy that counteracts one of the molecules released during migraine, was found successful in reducing the number of days that chronic migraine sufferers experienced headaches.
The World Health Organisation estimates that between 127m and 300m people around the world experience chronic migraine, defined as 15 or more headaches per month for at least three months. The disease can be debilitating and although a number of interventions exist, many only work for a certain time before they fail to prevent or relieve pain.
“This therapeutic approach offers new hope for people whose migraines cannot be treated with existing medicine,” says Dr Stephen D Silberstein, principal investigator of the HALO CM trial, professor of neurology and director of the Jefferson Headache Centre at the Jack & Vicki Farber Institute for Neuroscience at Thomas Jefferson University Hospital. “Our worldwide effort to evaluate this novel therapeutic approach has shown positive results and was safe in patients.”
Fremanezumab, a monocolonal antibody developed by Teva Pharmaceuticals, is a biological agent that binds to and blocks the action of a migraine-associated protein called calcitonin gene-related peptide (CGRP). Mounting evidence of its importance in migraines has made CGRP a focal point of research and drug development. The peptide is released at high levels during migraine in response to inflammation, and triggers a cascade effect that stimulates more CGRP release. This results in increasing sensitivity of the brain to pain. By blocking this peptide, doctors hope to break the cycle of increasing inflammation and increased pain sensitivity that contributes to migraine headaches.
Researchers from 132 sites across nine countries enrolled 1,130 patients and randomly assigned them to one of three groups: one that received quarterly treatments, a group that received one treatment per month, and one that received placebo injections. The trial lasted for 16 weeks, with a 12-week treatment window.
The results of the trial show that treatment with fremanezumab reduced the number of days patients experience headache by an average of 4.3 days with quarterly treatment and 4.6 days with monthly treatment. “We saw some patients with 100% reduction in migraine, others with 75% reduction,” says Silberstein. The level of response varied between patients.
The researchers also looked at how well the therapy worked relative to each patient’s headache burden. They calculated the percent of patients who had more than a 50% reduction in the number of days they experienced either a severe or moderate headache per month. Using this measure, the researchers saw that 37.6% of patients on the monthly regimen, and 40.8% on the quarterly regimen had at least a 50% reduction in the number of moderate headaches per month, compared to 18.1% in the placebo group.
The therapy had a favourable safety profile with the most common adverse event reported as irritation at injection site, which was reported in the placebo group as well. “If approved, this treatment would provide physicians with an important new tool to help prevent migraine, reduce a patient’s migraine load, and potentially help patients return to normal” says Silberstein.
Background: Fremanezumab, a humanized monoclonal antibody targeting calcitonin gene–related peptide (CGRP), is being investigated as a preventive treatment for migraine. We compared two fremanezumab dose regimens with placebo for the prevention of chronic migraine.
Methods: In this phase 3 trial, we randomly assigned patients with chronic migraine (defined as headache of any duration or severity on ≥15 days per month and migraine on ≥8 days per month) in a 1:1:1 ratio to receive fremanezumab quarterly (a single dose of 675 mg at baseline and placebo at weeks 4 and 8), fremanezumab monthly (675 mg at baseline and 225 mg at weeks 4 and 8), or matching placebo. Both fremanezumab and placebo were administered by means of subcutaneous injection. The primary end point was the mean change from baseline in the average number of headache days (defined as days in which headache pain lasted ≥4 consecutive hours and had a peak severity of at least a moderate level or days in which acute migraine–specific medication [triptans or ergots] was used to treat a headache of any severity or duration) per month during the 12 weeks after the first dose.
Results: Of 1130 patients enrolled, 376 were randomly assigned to fremanezumab quarterly, 379 to fremanezumab monthly, and 375 to placebo. The mean number of baseline headache days (as defined above) per month was 13.2, 12.8, and 13.3, respectively. The least-squares mean (±SE) reduction in the average number of headache days per month was 4.3±0.3 with fremanezumab quarterly, 4.6±0.3 with fremanezumab monthly, and 2.5±0.3 with placebo (P<0.001 for both comparisons with placebo). The percentage of patients with a reduction of at least 50% in the average number of headache days per month was 38% in the fremanezumab-quarterly group, 41% in the fremanezumab-monthly group, and 18% in the placebo group (P<0.001 for both comparisons with placebo). Abnormalities of hepatic function occurred in 5 patients in each fremanezumab group (1%) and 3 patients in the placebo group (<1%).
Conclusions: Fremanezumab as a preventive treatment for chronic migraine resulted in a lower frequency of headache than placebo in this 12-week trial. Injection-site reactions to the drug were common. The long-term durability and safety of fremanezumab require further study.
Stephen D Silberstein, David W Dodick, Marcelo E Bigal, Paul P Yeung, Peter J Goadsby, Tricia Blankenbiller, Melissa Grozinski-Wolff, Ronghua Yang, Yuju Ma, Ernesto Aycardi