MAIDENHEAD, UK, 4^th September 2023 — AbbVie (NYSE: ABBV) today announced that the Medicines and Healthcare products Regulatory Agency (MHRA) has granted a marketing authorisation for AQUIPTA^® (atogepant) for the prophylaxis of migraine in adults who have at least four migraine days per month.¹

Migraine is a severe and painful long-term health condition that approximately 1 in 7 people live with in the UK.⁶ Around 10 million adults in the UK are affected, but a report from the Migraine Trust suggests this number may be even higher.⁶ Although common, migraine is a disabling disease⁶ and can affect people’s ability to work, socialise and care for dependents, along with having an impact on mental health.⁷ In 2020, the National Health Service England reported that hospital admissions for headaches and migraines had increased by 14% over the previous five years,⁸ and in 2018 lost productivity from migraine-related absence from work was estimated to cost around £8.8 billion (using the Global Burden of Disease study, 2016 adult migraine prevalence data).⁹ Despite the prevalence and impact of migraine, people report their experience is often dismissed or trivialised in wider society.⁶ This has contributed to the sense of burden and invisibility that many feel when accessing care.⁶

“Many patients struggle for years to find an effective treatment. During this time, many are resigned to living with the debilitating effects of migraine; it shouldn’t be this way,” said Professor Peter Goadsby, Honorary Consultant Neurologist, King’s College Hospital. “Atogepant is a new addition to the CGRP receptor antagonists (or gepants) treatment class and has shown promising results in clinical trials for the reduction of migraine and headache days. This marketing authorisation is an important step for the migraine community, increasing the range of treatment options that we can prescribe to them.”

The marketing authorisation is supported by data from two pivotal Phase 3 clinical studies evaluating atogepant 60 mg once-daily in adults living with episodic (ADVANCE) and chronic (PROGRESS) migraine.^1-5 In both trials, the treatment met their primary endpoint of a change from baseline in mean monthly migraine days across 12 weeks vs. placebo. Additionally, the treatment achieved significant reductions from baseline in several secondary efficacy endpoints compared to placebo: mean monthly headache days and mean monthly acute medication days.^{1, 4, 5} Atogepant was generally well tolerated, with the most commonly reported adverse reactions being nausea (7%), constipation (7%) and fatigue/somnolence (5%).¹ The majority of adverse events were mild, and none were serious.¹

“There is a common misconception that migraine is ‘just a headache,’ but for many patients, migraine has a devastating impact on their everyday life,” said Belinda Byrne, Medical Director, AbbVie UK. “AbbVie is committed to advancing the standards of care for people living with migraine and we are delighted that the MHRA has provided marketing authorisation for this new medication. We are currently working with the regulatory authorities to bring this potential treatment to eligible patients as soon as possible.”

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▼This medicine is subject to additional monitoring. This will allow quick identification of new safety information. You can report side effects directly via the Yellow Card Scheme at https://yellowcard.mhra.gov.uk/ or via the Medicines and Healthcare products Regulatory Agency (MHRA) Yellow Card app, available in the Google Play or Apple App Stores. Adverse events should also be reported to AbbVie at GBPV@abbvie.com. By reporting side effects, you can help provide more information on the safety of this medicine.

UK media contacts:

Sophia James                                                             Anastasios Koutsos

AbbVie UK                                                                  Health Unlimited

T: +44 (0)7977 055 997                                              T: +44 20 7751 5083

E: sophia.e.james@abbvie.com                                 E: anastasios.koutsos@unlimitedgroup.com

NOTES TO EDITORS:

About Migraine

Migraine is a disabling primary headache disorder, typically involving recurrent moderate to severe pulsatile headaches and neurological symptoms.¹⁰ Migraine attacks can involve the whole body, with sensitivity to light, sensitivity to sounds and smells, nausea, and fatigue.¹¹ It is highly prevalent, standing as the second highest cause of disability globally,¹⁰ with an estimated 10 million people living with migraine in the UK.⁶

Migraine can be episodic or chronic. People living with chronic migraine experience headaches or migraine for 15 or more days per month, with at least eight of those days associated with migraine for three or more months.^1,12 It is differentiated from episodic migraine, which is characterised by 4–14 headache days per month,^1,12 greater prevalence of comorbid conditions, as well as higher frequency of headache and migraine days.¹² Migraine can affect people’s ability to work, socialise and care for dependents, along with having an impact on mental health.⁹ Despite the prevalence and impact of migraine, it’s often underdiagnosed and not optimally treated.⁹

About AQUIPTA^® (atogepant)

Atogepant is a once-daily, orally administered calcitonin gene-related peptide (CGRP) receptor antagonist specifically developed for the prophylaxis of migraine in adults who have at least four migraine days per month.¹ Atogepant blocks the binding of the CGRP to the receptor and antagonises CGRP receptor function.^{1,12, 13} CGRP and its receptors are expressed in regions of the nervous system associated with migraine pathophysiology.^1,12 Studies have shown that CGRP levels are elevated during migraine attacks¹² and selective CGRP receptor antagonists confer clinical benefits in migraine.^2,3,5

About the atogepant Phase 3 clinical trial programme^3,5,

Atogepant was evaluated for the prophylaxis of migraine in two pivotal studies across the migraine spectrum in chronic and episodic migraine.

The data presented below are from the modified intent-to-treat (mITT) population, as per the pre-specified analysis in the published studies. It therefore may differ slightly from the data in the AQUIPTA^® Summary of Product Characteristics, which uses the off-treatment hypothetical estimand (OTHE) population at the request of the European Medicines Agency.

Episodic migraine³

Atogepant was evaluated for the prophylaxis of episodic migraine (4–14 headache days per month) in a randomised, multicentre, double-blind, placebo-controlled study (ADVANCE). A total of 910 patients were randomised 1:1:1:1 with N=222 to receive AQUIPTA 60 mg and N=214 for placebo once daily for 12 weeks.

The primary efficacy endpoint was the change from baseline in mean monthly migraine days (MMD) across the 12-week treatment period. Additional endpoints included the change from baseline in mean monthly headache days, the change from baseline in mean monthly acute medication use days, the proportion of patients achieving at least a 50% and 75% reduction from baseline in mean MMD (3‑month average), and change from baseline at 12 weeks for Headache Impact Test HIT-6 total score and Migraine Specific Quality of Life Questionnaire version 2.1, MSQ v2.1 Role Function-Restrictive RFR domain score.

Atogepant demonstrated the following results (N=222 for atogepant and N=214 for placebo):

Primary efficacy endpoint

• -4.2 days change from baseline (7.8 days) in mean MMD across 12 weeks compared to -2.5 with placebo from baseline (7.5 days), mean difference vs. placebo: -1.7, 95% CI -2.3 to -1.2, p<0.001

Secondary endpoints

• -4.2 change from baseline (9.0 days) in mean monthly headache days across 12 weeks compared to -2.5 with placebo from baseline (8.4 days), mean difference vs. placebo: -1.7, 95% CI -2.3 to -1.1, p<0.001.
• -3.9 days from baseline (6.9 days) of acute medication use per month for migraine attacks across 12 weeks compared to -2.4 days per month with placebo from baseline (6.5 days), mean difference vs. placebo: -1.5, 95% CI -2.0 to -1.0, p<0.001.
• 135 patients achieved at least a 50% reduction from baseline in mean MMD across 12 weeks compared to 62 with placebo, odds ratio vs. placebo: 3.8, 95% CI 2.6 to 5.7, p<0.001.
• +31.2 mean change in the effect of migraine on daily life and ability to function at work and social situations from baseline (46.8 days) in the MSQ v2.1 Role Function-Restrictive RFR at week 12 compared to +20.4 with placebo from baseline (46.8 days), difference vs. placebo: 10.8, 95% CI 6.4 to 15.2, p<0.001.
• -9.1 mean change in quality of life from baseline (63.8 days) in the HIT-6 score at week 12 compared to -5.2 with placebo from baseline (64.6 days), difference vs. placebo: -3.9, 95% CI  -5.4 to -2.5, p<0.001.¹

Chronic migraine⁵

Atogepant was evaluated for the prophylaxis of chronic migraine (15 or more headache days per month with at least eight migraine days) in a randomised, multicentre, double-blind, placebo-controlled study (PROGRESS). A total of 778 patients were randomised 1:1:1 with N=256 to receive AQUIPTA 60 mg and N=246 for placebo once daily for 12 weeks.

The primary efficacy endpoint was the change from baseline in mean MMD across the 12‑week treatment period. Additional endpoints included the change from baseline in mean monthly headache days, the change from baseline in mean monthly acute medication use days, the proportion of patients achieving at least a 50% and 75% reduction from baseline in mean MMD (3-month average), and change from baseline at week 12 for HIT-6 total score and MSQ v2.1 RFR domain score.

Atogepant demonstrated the following results (N=256 for atogepant and N=246 for placebo):

Primary endpoint

• -6.9 days change from baseline (19.2 days) in mean MMD across 12 weeks compared to -5.1 days with placebo from baseline (18.9 days), mean difference vs. placebo: -1.8, 95% CI -2.9 to -0.8), p=0.0009.

Secondary endpoints

• -7.0 days change from baseline (21.5 days) in mean monthly headache days across 12 weeks compared to -5.1 days with placebo from baseline (21.4 days), mean difference vs. placebo: -1.9, 95% CI -2.9 to -0.8, p=0.0009.
• -6.2 days of acute medication use per month from baseline (15.5 days) for migraine attacks across 12 weeks compared to -4.1 days per month with placebo from baseline (15.4 days), mean difference vs. placebo: -2.1, 95% CI -3.1 to -1.1, p=0.0009.
• +23.3 mean change in the effect of migraine on daily life and ability to function at work and social situations from baseline (43.6 days) in the MSQ v2.1 RFR at week 12 compared to +17.2 mean change with placebo from baseline (43.6 days), mean difference vs. placebo: 6.1, 95% CI 2.5 to 9.8, p=0.0009.
• -7.8 mean change from baseline in quality of life from baseline (64.2) in the HIT-6 score at week 12 compared to -5.2 with placebo from baseline (64.0), difference vs. placebo: -2.7, 95% CI -4.0 to -1.3, p<0.0024.

Safety profile¹

The safety of atogepant was evaluated in 2,657 patients with migraine who received at least one dose of atogepant. Of these, 1,225 patients were exposed to atogepant for at least six months and 826 patients were exposed for 12 months.

The most commonly reported adverse drug reactions were nausea (7%), constipation (7%), and fatigue/somnolence (5%). The majority of the cases were mild, and none were serious. The adverse reaction that most commonly led to discontinuation was nausea (0.6%).

For full information on the adverse reactions of atogepant, please refer to the Summary of Product Characteristics.

About AbbVie in Neuroscience

At AbbVie, our commitment to preserving the personhood of people around the world living with neurological and psychiatric disorders is unwavering. With more than three decades of experience in neuroscience, we are providing meaningful treatment options today and advancing innovation for the future. AbbVie's Neuroscience portfolio consists of licensed treatments in neurological conditions, including migraine, movement disorders, and psychiatric disorders, along with a robust pipeline of transformative therapies. We have made a strong investment in research and are committed to building a deeper understanding of neurological and psychiatric disorders. Every challenge makes us more determined and drives us to discover and deliver advancements for those impacted by these conditions, their care partners, and clinicians. For more information about AbbVie, please visit us at www.abbvie.co.uk. Follow @abbvieuk on Twitter or YouTube.

About AbbVie

AbbVie's mission is to discover and deliver innovative medicines and solutions that solve serious health issues today and address the medical challenges of tomorrow. We strive to have a remarkable impact on people's lives across several key therapeutic areas – immunology, oncology, neuroscience, and eye care – and products and services in our Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at www.abbvie.co.uk. Follow @abbvieuk on Twitter or YouTube.

References

1. AQUIPTA^® (Atogepant) Summary of Product Characteristics. [Last accessed: August 2023].

2. Ashina M, et al. Once-daily oral atogepant for the long-term preventive treatment of migraine: Findings from a multicenter, randomized, open-label, phase 3 trial. Headache. 2023 Jan;63(1):79–88.

3. Ailani J, et al. Atogepant for the Preventive Treatment of Migraine. N Engl J Med. 2021;385:695–706.

4. Lipton RB, et al. Effect of atogepant for preventive migraine treatment on patient-reported outcomes in the randomized, double-blind, phase 3 ADVANCE trial. Neurology. 2023 Feb 21;100(8):e764–e777.

5. Pozo-Rosich P, et al. Atogepant for the preventive treatment of chronic migraine (PROGRESS): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. Available from: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)01049-8/fulltext [Last accessed: August 2023]

6. The Migraine Trust. State of the Migraine Nation Dismissed for too long: Recommendations to improve migraine care in the UK. Available from: https://migrainetrust.org/wp-content/uploads/2021/09/Dismissed-for-too-long_Recommendations-to-improve-migraine-care-in-the-UK.pdf [Last accessed: August 2023].

7. Begasse de Dhaem O and Sakai F. Migraine in the workplace. eNeurologicalSci. 2022 Jun 6;27:100408.

8. NHS England. News: Improved NHS migraine care to save thousands of hospital stays. Available from: https://www.england.nhs.uk/2020/01/improved-nhs-migraine-care/#:~:text=The%20number%20of%20admissions%20to,emergency%20admissions%20in%202018%2F19. [Last accessed: August 2023].

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