Atogepant Tablets (Qulipta)
November 15, 2021 4 minutes read
By William Elliott, MD, FACP, and James Chan, PharmD, PhD
Dr. Elliott is Assistant Clinical Professor of Medicine, University of California, San Francisco.
Dr. Chan is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco.
The FDA has approved a second non-injectable calcitonin gene-related peptide (CGRP) receptor antagonist to prevent episodic migraine in adults. Atogepant is an orally administered, small-molecule solution similar to rimegepant (Nurtec ODT), which the FDA approved in February 2021 for acute treatment and in May 2021 as preventive treatment of episodic migraine. The FDA granted atogepant tablets priority review. It is distributed as Qulipta.
INDICATIONS
Atogepant can be prescribed to prevent episodic migraine in adults.1
DOSAGE
The recommended dose is 10 mg, 30 mg, or 60 mg taken orally once daily with or without food.1 The 10 mg dose is recommended for patients on a strong CYP3A4 inhibitor, those with severe renal impairment, or those with end-stage renal disease (creatinine clearance < 30 mL/min). Patients taking an organic anion transport protein inhibitor should be on 10 mg or 30 mg of atogepant. The dose should be 30 mg or 60 mg for those on strong and moderate CYP3A4 inducers. Atogepant is available as 10 mg, 30 mg, and 60 mg tablets.
POTENTIAL ADVANTAGES
Atogepant provides an alternative orally administered, preventive treatment instead of monthly subcutaneous injections (e.g., erenumab, galcanezumab), an every-three-month subcutaneous injection (e.g., fremanezumab), or intravenous infusion every three months (e.g., eptinezumab).
POTENTIAL DISADVANTAGES
Atogepant requires daily dosing, with potential for inconsistent adherence, while monoclonal antibodies are given monthly up to every three months. The most commonly reported adverse reactions (vs. placebo) were nausea (5%-6% vs. 3%), constipation (6% vs. 1%), and fatigue/somnolence (4%-6% vs. 3%).1 Atogepant is an oral tablet, while rimegepant can be taken orally or sublingually.
COMMENTS
The efficacy of atogepant was evaluated in two randomized, double-blind, placebo-controlled, 12-week studies. Study 1 (n = 910) and study 2 (n = 629) were conducted in subjects who reported about eight migraine days per month, with a range of four to 14 days.1-3 Participants were mainly female (87%-89%) and white (76%-83%). Subjects were permitted to use acute headache treatment, except for those drugs that act on the CGRP pathway (e.g., gepants). Subjects with cardiovascular risk (e.g., myocardial infarction, stroke, or transient ischemic attacks) were excluded.
In study 1, subjects were randomized 1:1:1:1 to atogepant 10 mg, 30 mg, 60 mg, or placebo. In study 2, randomization was 2:1:2:2 placebo, 10 mg, 30 mg, and 60 mg, respectively. The primary efficacy endpoint was the change from baseline in mean monthly migraine days (MMD) across the 12-week treatment period. Study 1 also included some secondary endpoints that included ≥ 50% MMD responders across 12 weeks, health outcomes (Activity Impairment in Migraine-Diary [AIM-D]) that assesses performance of daily activities (PDA) and physical impairment (PI), and the Migraine-Specific Quality of Life Questionnaire (MSQ).
The MMD declined from a baseline of 3.7 days for the 10 mg dose, 3.9 days for 30 mg, and 4.2 days for 60 mg vs. -2.5 days for placebo (P < 0.001 for all comparisons to placebo). Benefit was observed in weeks 1 to 4. The percentages of those demonstrating a 50% or greater response were 56% for 10 mg, 59% for 30 mg, and 61% for 60 mg vs. 29% for placebo. Significant improvement was demonstrated for MSQ for all three doses, and significant improvements in AIM-D domain and PI Domain were seen for 30 mg and 60 mg only. For study 2, MMD reductions from baseline were four days for the 10 mg dose, 3.8 days for the 30 mg dose, and 3.6 days for the 60 mg dose vs. 2.8 days for placebo.
CLINICAL IMPLICATIONS
Migraine is a common disorder, with a worldwide prevalence of 14.4%.4 CGRP has become a popular target for preventive treatment of migraines. Atogepant is the second non-injectable CGRP available for such treatment after rimegepant. There are no direct comparisons between the two small-molecule receptor antagonists. An indirect transitive comparison between placebo-controlled atogepant and rimegepant clinical trials with similar subject demographics and study design suggested possible differences in efficacy in favor of atogepant. Difference from placebo in MMD ranged from -1.2 days to -1.7 days for atogepant across 12 weeks vs. -0.8 days for rimegepant.1,5 Responders with ≥ 50% improvement ranged from 56%-61% for atogepant (29% for placebo; P < 0.001) vs. 49.1% for rimegepant (41.5% for placebo; P = 0.044). There are three monoclonal antibodies (eptinezumab, galcanezumab, fremanezumab) that target the CGRP ligand, and one (erenumab) that targets the CGRP receptor.
A meta-analysis of results from randomized, controlled trials of the erenumab, fremanezumab, and galcanezumab suggests similar effectiveness and safety.6 After three treatment cycles (12 weeks), the overall MMD difference between treatment and placebo was -1.80 days.6 Atogepant offers a new oral therapeutic option for prevention of episodic migraine in adults. The cost for a 30-day supply is $991.
REFERENCES
- AbbVie. Qulipta prescribing information. September 2021.
- Ailani J, Lipton RB, Goadsby PJ, et al. Atogepant for the preventive treatment of migraine. N Engl J Med 2021;385:695-706.
- Goadsby PJ, Dodick DW, Ailani J, et al. Safety, tolerability, and efficacy of orally administered atogepant for the prevention of episodic migraine in adults: A double-blind, randomised phase 2b/3 trial. Lancet Neurol 2020;19:727-737.
- GBD 2016 Neurology Collaborators. Global, regional, and national burden of neurological disorders, 1990-2016: A systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol 2019;18:459-480.
- Croop R, Lipton RB, Kudrow D, et al. Oral rimegepant for preventive treatment of migraine: A phase 2/3, randomised, double-blind, placebo-controlled trial. Lancet 2021;397:51-60.
- Alasad YW, Asha MZ. Monoclonal antibodies as a preventive therapy for migraine: A meta-analysis. Clin Neurol Neurosurg 2020;195:105900.
Atogepant can be prescribed to prevent episodic migraine in adults.
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