AAN, AHS Issue Updated Guideline on Migraine Prevention, Atogepant Meets End Points in Phase 3 Trial, Trientine Enters Phase 3 Trial

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Welcome to the Neurology News Network, my name is Louie Pasculli and here’s a look at some of the top stories in Neurology.

The American Academy of Neurology (AAN) and American Headache Society (AHS) have issued an updated practice guideline on pharmacologic migraine prevention in adults. The guidelines are published in Neurology and replace recommendations that were last updated in 2012.^1,2 Drawing on a systematic review of evidence through June 6, 2024, the guideline reflects newer preventive drug classes, including CGRP-targeted therapies, and offers graded recommendations on when to start preventive therapy, how to choose among medications, and how to manage treatment in populations such as pregnant or lactating patients, older adults, and those with comorbidities or medication overuse.^1,3

Recommendations carry a graded level of obligation: Level A ("must") is very strong, Level B ("should") is strong, and Level C ("may") is weak, reflecting the panel's confidence in the evidence.

The updated guideline applies to adults with episodic or chronic migraine and provides recommendations on when to initiate preventive treatment and how to select among available therapies. Clinicians should offer preventive treatment to patients with at least 4 migraine or moderate to severe headache days per month, or those with substantial migraine-related disability. Rather than identifying a single preferred medication, the guideline recommends considering efficacy, tolerability, long-term safety, cost, and patient preferences, while incorporating newer options such as CGRP-targeted therapies and botox. The guidance also provides considerations for specific populations, including pregnant and lactating patients, older adults, and those with comorbidities or medication overuse, and recommends assessing treatment response after 8 to 12 weeks for most medications and 24 weeks for botox.

In other news, AbbVie recently reported that atogepant, an oral calcitonin gene-related peptide (CGRP) receptor antagonist currently approved for migraine prevention in adults, met the primary end point and all secondary end points among patients with menstrual migraine compared with placebo in the phase 3 LUNA study (NCT06806293). The company noted that it plans regulatory submissions worldwide and presentation of complete findings at future medical meetings.⁴

“Menstrual migraine attacks are generally more severe and more difficult to treat, making timely intervention particularly important,” Cristina Tassorelli, MD, PhD, professor of neurology and director of the Headache Science Centre at IRCCS Mondino Foundation, University of Pavia, Italy, said in a statement.⁴ "LUNA is the first study of a CGRP-targeted treatment to report positive results specifically in menstrual migraine and meets an important unmet need for women."

Atogepant reduced perimenstrual migraine days by an average of 1.20 days, compared with 0.40 days for placebo. The between-group difference was 0.80 days in favor of atogepant (P <.0001). The trial also met all 8 ranked secondary end points (all, P <.0001), according to AbbVie. These measures included headache days, moderate or severe headache days, acute medication use, functional disability, cognitive function, and responder outcomes. AbbVie reported that safety findings were consistent with the established profile of atogepant and that no new safety signals emerged.

Changing gears, Orphalan has initiatedTRADITiONAL (NCT07465718), a new global phase 3 trial comparing an investigational once-daily formulation of trientine tetrahydrochloride with D-penicillamine as first-line treatment for Wilson disease. The 48-week study will assess efficacy, safety, tolerability, and treatment satisfaction in patients aged 8 years or older.⁵

“Successful management of Wilson disease requires lifelong therapy, and current treatment regimens can be complex and burdensome for many patients, posing significant challenges with adherence,” Omar Kamlin, MD, chief medical officer at Orphalan, said in a statement.⁵ "The initiation of the global TRADITiONAL Study in the USA reflects Orphalan's commitment in addressing the unmet needs of Wilson disease patients by investigating a therapeutic approach which may simplify the treatment burden."

TRADITiONAL is a randomized, parallel-group, open-label, multicenter study enrolling symptomatic and asymptomatic patients with Wilson disease. Eligible participants must be treatment-naive or naive to chelator therapy. Symptomatic patients who have received zinc salts for no more than 28 days may also qualify. Following an approximately 4-week screening period, participants will be randomly assigned to 48 weeks of trientine tetrahydrochloride or D-penicillamine.⁶

To read the full pieces and to get more direct access to expert insight, head to NeurologyLive.com. Be sure to tune in next week to remain informed on the latest in neurology. I’m Louie Pasculli, thanks for watching Neurology News Network.

REFERENCES
1. Potrebic S, Tanveer S, Becker WJ, et al. Pharmacologic Treatment for Migraine Prevention in Adults Practice Guideline Recommendations: Report of the AAN Guidelines Subcommittee and the American Headache Society. Neurology. 2026;107(7):e214881. doi:10.1212/WNL.0000000000214881
2. AAN and AHS issue updated guideline on migraine prevention medications for adults. News release. American Academy of Neurology. August 31, 2026. Accessed September 1, 2026. https://www.aan.com/PressRoom/Home/PressRelease/5361
3. Pringsheim T, Smith DB, Tanveer S, et al. Systematic Review of Pharmacologic Treatment for Migraine Prevention in Adults: Report of the AAN Guidelines Subcommittee and the American Headache Society. Neurology. 2026;107(7):e218112. doi:10.1212/WNL.0000000000218112
4. AbbVie Extends Migraine Leadership with Positive Phase 3 Atogepant Results in Menstrual Migraine. News release. AbbVie. September 10, 2026. Accessed Septemeber 10, 2026. https://news.abbvie.com/2026-09-10-AbbVie-Extends-Migraine-Leadership-with-Positive-Phase-3-Atogepant-Results-in-Menstrual-Migraine
5. Orphalan initiates global phase 3 TRADITiONAL study of investigational once-daily trientine therapy in Wilson disease. News release. Orphalan. September 7, 2026. Accessed September 9, 2026. https://www.orphalan.com/orphalan-initiates-global-phase-3-traditional-study-of-investigational-once-daily-trientine-therapy-in-wilson-disease/
6. ClinicalTrials.gov. Study NCT07465718: TRADITiONAL study of trientine tetrahydrochloride in Wilson disease. US National Library of Medicine.