Phase 3 STRIVE and ARISE Trials Show Efficacy, Safety for Erenumab in Migraine Prevention

Deborah Brauser

April 26, 2017

BOSTON — Treatment with the experimental calcitonin gene-related peptide (CGRP) antibody erenumab (AMG 334, Amgen and Novartis) can reduce the frequency of episodic migraine — without the side effect profile commonly found with other migraine medications, suggest findings from two phase 3, randomized controlled trials.

STRIVE, which assessed 955 adults with episodic migraine, showed that patients who received subcutaneous monthly doses of erenumab at 140 mg or 70 mg for 24 weeks had a significantly greater reduction in monthly migraine days (MMDs) compared with those who received matching placebo (the primary endpoint).

Both dosing groups also had greater reductions in migraine-specific medication days and greater improvements in physical impairment and everyday activities scores.

But lead author, Peter Goadsby, MD, PhD, professor of neurology at the University of California, San Francisco, told Medscape Medical News that equally important is the lack of significant differences between the active drug and placebo groups for serious or nonserious adverse events (AEs).

"At the moment we prescribe by which things you don't like. We ask, ‘Do you want to be tired? Do you want to put on weight or be grumpy or sleepy?’ And they pick the one they dislike the least, which is a crazy way to treat people," said Dr Goadsby, who is also director of the NIHR-Wellcome Trust Clinical Research Facility at King's College Hospital, London, United Kingdom.

"That's a real burden for patients, but it looks like this new treatment frees them from that — and that's fantastic." He presented the results here at the American Academy of Neurology 2017 Annual Meeting (AAN).

In a session later in the day, David Dodick, MD, Department of Neurology at Mayo Clinic, Scottsdale, Arizona, presented findings from the ARISE trial, which assessed efficacy and safety of erenumab at 70 mg only vs placebo in 577 adult patients with episodic migraine.

It also showed that those receiving the active treatment had significant reductions in MMDs, increased odds of achieving a 50% or greater reduction in MMD, and reduced days per month using migraine-specific medication. In addition, type and frequency of adverse events were similar across the groups.

Targets Monoclonal Antibody

While CGRP "plays an important role in migraine pathophysiology," erenumab is a fully human monoclonal antibody that targets and inhibits the CGRP receptor, noted Dr Goadsby.

The treatment was being co-developed by Amgen and Novartis, with Amgen having commercialization rights in the United States, Canada, and Japan and Novartis having European commercialization rights.

However, a statement released by Amgen on April 24 announced that both companies will now co-commercialize the treatment in the United States, Amgen will have exclusive rights in Japan, and Novartis will receive exclusive rights in Canada while retaining the rest of its commercialization rights.

The medication has not yet been approved by the US Food and Drug Administration (FDA), but Amgen stated in its release that the findings from these two phase 3 trials, as well as a successful phase 2 study, "will help support discussions with regulatory agencies, with filing anticipated in the second quarter of 2017."

In STRIVE, 955 patients were randomly assigned to one of three groups: subcutaneous erenumab at 70-mg (n = 317; 85% women; 89% white; mean age, 41.1 years) or 140-mg (n = 319; 85% women; 92% white; mean age, 40.4 years) doses or matching placebo (n = 319; 86% women; 87% white; mean age, 41.3 years).

Measures included the Physical Impairment and the Impact on Everyday Activities scores on the Migraine Physical Function Impact Diary (MPFID-PI and MPFID-EA, respectively).

The erenumab 70-mg and 140-mg groups had 3.2- and 3.7-day reductions in MMDs, respectively, from baseline to weeks 13 to 24 vs a 1.8-day reduction for the placebo group (both comparisons, P < .001).

In addition, 43.3% and 50% of the active treatment groups, respectively, vs 27% of the placebo group had 50% or greater reductions in MMDs (odds ratios [ORs], 2.13 and 2.81). And there were 1.1, 1.6, and 0.2 reductions in days for the use of migraine-specific medications (all comparisons, P < .001).

Patients receiving the 70-mg and 140-mg doses also had improvements by 4.2 and 4.8 points on the MPFID-PI vs 2.4 points for those receiving placebo; they had improvements of 5.5 and 5.59 points vs 3.3 points, respectively, on the MPFID-EA (all comparisons, P < .001).

Finally, the rate of AEs was similar between the groups, with 2.5%, 1.9%, and 2.2%, respectively, reporting serious AEs. The most common AEs were nasopharyngitis and upper respiratory tract infection.

Migraine-Specific Preventive

"Migraine is the biggest cause of disability due to neurological problems on the planet. There's no preventative specific for migraine, but this is a migraine-specific preventative," said Dr Goadsby. "What isn't exciting about that?"

Session co-moderator and member of the AAN Science Committee, Deborah Hall, MD, PhD, associate professor of neurology at Rush Medical College, Chicago, Illinois, echoed that thought by also calling the findings "very exciting."

"Migraine is so prevalent, even among neurologists. So I would suspect that there were a lot of people in the room today that could benefit from these compounds," Dr Hall later said to Medscape Medical News.

"I also appreciated that a question was brought up about the safety of long-term use. And hopefully, as Dr Goadsby said, this will be safe and people can take this chronically."

Dr Hall noted that many of the other medications used for migraine prevention "have side effects and become problematic — maybe not when you start them but later on. So this compound shows great promise in not being a problem for patients."

ARISE

In the ARISE trial, 577 patients (mean MMDs at baseline, 8.3) were randomly assigned to monthly treatment with erenumab 70 mg (n = 286; 85.7% women, 90.6% white; mean age, 42.3 years) or placebo (n = 291; 84.9% women; 89.0% white; mean age, 42.2 years).

It showed that the active-treatment group, compared with the placebo group:

  • had a reduction of 2.9 days vs 1.8 days, respectively, in MMDs from baseline to weeks 9 to 12 of treatment (P < .001);

  • had a group rate of 39.7% vs 29.5% for a 50% or greater reduction in MMDs (OR, 1.6; P = .01); and

  • had a reduction of 1.2 vs 0.6 in acute migraine-specific medication days (P = .002).

There were no statistically significant between-group differences in score improvements on the MPFID-PI or MPFID-EA.

Any AEs were reported by 48.1% of patients receiving erenumab and 54.7% of those receiving placebo, with 1.1% vs 1.7% reporting any serious AEs. In addition, 6.4% vs 4.8% reported upper respiratory tract infection, 6.0% vs 4.2% reported injection site pain, and 5.3% vs 5.9% reported nasopharyngitis.

Edward Bertram, MD, University of Virginia in Charlottesville and a moderator at Dr Dodick's session, called this study "a very interesting approach" and noted that it will be good to see in the future how well it works in a wider, more generalized community of patients with migraine.

"But overall, it's an interesting and possibly promising result," he commented.

FDA Fast-Track Status?

Vice chair of the AAN Science Committee, Natalia Sana Rost, MD, noted during a press conference that the monoclonal antibody used in both STRIVE and ARISE is, unlike other monoclonals, receptor-specific.

"So we do not expect in this case for there to be any implications for long-term side effects related to, for example, immunity," said Dr Rost, who is director of the Acute Stroke Service at Massachusetts General Hospital and associate professor of neurology at Harvard Medical School, Boston, Massachusetts.

"We're excited to have disease-specific treatment and a biologic that is developed to identify a very precise target," she said. "But we'll need to be mindful," still, of watching for long-term effects.

Asked whether he thinks the FDA will approve the medication based on these two trials, Dr Goadsby said, "Yes, and I'd be very surprised if they didn't fast-track it. I think the FDA gets that migraine is disabling and common."

Both trials were funded by Amgen. Dr Goadsby reported that he has "consulted for all the companies that are interested in CGRP development in migraines." Dr Dodick reported receiving consulting fees from Amgen, Alder, Allergan, Eli Lilly, eNeura, Boston Scientific, Teva, Novartis, Autonomic Technologies, Scion Neurostim, Tonix, Trigemina, Supernus, Xenon, GBS, and Xalan; honoraria from Sage Publishing, Wiley, and UptoDate; and royalties from Oxford and Cambridge University Presses. Dr Hall, Dr Betram, and Dr George have disclsoed no relevant financial relationships.

American Academy of Neurology 2017 Annual Meeting (AAN). Clinical Trials Plenary, Talk 9, and Emerging Science Session, Talk 1; both presented April 25, 2017.

Follow Deborah Brauser on Twitter: @MedscapeDeb. For more Medscape Neurology news, join us on Facebook and Twitter.

Comments

3090D553-9492-4563-8681-AD288FA52ACE
Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as:

processing....

Recommendations