DUBLIN, June 11, 2018 /PRNewswire/ — Allergan plc, (NYSE: AGN), a leading global pharmaceutical company, today announced positive results from CGP-MD-01, a Phase 2b/3 clinical trial evaluating the efficacy, safety, and tolerability of orally administered atogepant. All active treatment arms of atogepant met the primary endpoint across all doses and dose regimens, with a statistically significant reduction from baseline in monthly migraine/probable migraine (MPM) headache days in patients with episodic migraine treated with atogepant compared with placebo for 12 weeks. Atogepant is Allergan’s second orally-administered investigational calcitonin gene-related peptide (CGRP) receptor antagonist in development for migraine prevention. Atogepant follows ubrogepant, Allergan’s first oral investigational CGRP antagonist for the acute treatment of migraine, which reported two positive Phase 3 pivotal trial results earlier this year. Allergan will continue with its phase 3 program for atogepant following discussions with regulatory authorities.
In study CGP-MD-01 834 U.S. adult patients were randomized (2:1:2:1:2:1) to placebo, 10-mg QD, 30-mg QD, 30-mg BID, 60-mg QD, and 60-mg BID respectively, and treated under double blind conditions 12 weeks for the prevention of episodic migraine. Efficacy analyses were based on the modified ITT (mITT) population of 795 patients. The primary efficacy endpoint was the change from baseline in mean monthly migraine/probable migraine (MPM) headache days across the 12-week treatment period.
All active treatment groups demonstrated a statistically significant reduction from baseline in the primary efficacy parameter (10 mg QD vs placebo, p=0.0236; 30 mg QD vs placebo, p=0.0390; 60 mg QD vs placebo, p=0.0390; 30 mg BID vs placebo; p=0.0034, 60 mg BID vs placebo, p=0.0031). The reported p-values are adjusted for multiple comparisons by controlling the overall type I error rate of the study at 5%, 2-sided.
“We are extremely pleased to share these positive results for atogepant — our first phase 2b/3 study in Episodic Migraine—which represent a tremendous opportunity in the prevention of migraine, with a convenient, oral dosage form that is currently unavailable,” said David Nicholson, Chief Research and Development Officer, Allergan. “Allergan has been studying migraine treatment for decades and is committed to addressing unmet needs through product innovation for patients who are hopeful for new options that can make a true difference in their daily lives.”
In the CGP-MD-01 trial, atogepant was well tolerated. The most common adverse events were nausea, fatigue, constipation, nasopharyngitis, and urinary tract infection which were reported with a frequency >5% in at least 1 atogepant treatment arm and greater than placebo. There was no signal of hepatotoxicity with atogepant in this study with daily administration over 12 weeks. The liver safety profile for atogepant was similar when compared to placebo.
“The positive results from this study show that oral atogepant has a compelling profile relative to other treatment options on the market and in development for the prevention of migraine. We are excited about the prospects for this product and rapidly moving to the next stage of development,” said Bill Meury, Chief Commercial Officer at Allergan. “Allergan has one of the most innovative and deepest product lines for migraine in the industry, with Botox approved for the prevention of chronic migraine and oral atogepant and ubrogepant in development for the prevention and acute treatment of migraine.”
“These exciting results demonstrate the potential for atogepant for a broad spectrum of migraine patients. The efficacy and safety across doses and dose regimens show promise in a patient population with high unmet treatment needs,” said Dr. Peter Goadsby, Neurologist and Professor at Kings College, London and University of California, San Francisco. “Results from this atogepant trial provide continued evidence for the clinical potential of oral CGRP antagonists and the substantial value of progressing research and developing new treatments for migraine patients.”
About the CGP-MD-01 study
Study CGP-MD-01 is a Phase 2b/3, multicenter, randomized, double-blind, placebo-controlled, parallel-group study conducted in the United States.
The study includes a 4-week screening/baseline period prior to randomization, a 12-week double-blind treatment period, and a 4-week safety follow-up period.
To be eligible for study participation, patients must be 18 to 75 years of age (inclusive), have a history of migraine with or without aura for at least 1 year, and experience between 4 to 14 migraine/probable migraine headache days per month on average in the 3 months prior to Visit 1 and in the 28-day baseline period.
Of the 834 randomized patients, the mean age was 40.1 years. Patients were mostly female (86.5%), white (76.1%) or black/African American (20.4%) with a mean Body Mass Index (BMI) of 30.11. Patients enrolled had a history of migraine for an average of 19.37 years with 50.4% of patients diagnosed with Migraine Without Aura and 49.4% of patients diagnosed either with Migraine with Aura or both Migraine With/Without Aura. A total of 82% of patients completed the study. The rate of discontinuation was similar across all treatment groups.
About Atogepant
Atogepant is a novel, highly potent, orally-administered CGRP receptor antagonist in development for the prevention of migraine. CGRP and its receptors are expressed in regions of the nervous system associated with migraine pathophysiology. It is chemically distinct from ubrogepant, our orally-administered CGRP receptor antagonist for the acute treatment of migraine, with a higher potency and longer half-life, making it suitable for preventive treatment.
Oral CGRP receptor antagonism offers a novel, and validated mechanism of action in a patient friendly dosage form for the prevention of migraine.
About Migraine
Migraine is a chronic disease with episodic attacks defined by neurological symptoms such as headache pain, sensitivity to light, sound, and nausea that are often incapacitating. It is highly prevalent, affecting approximately 1 in 7 individuals, and is associated with significant disability leading to societal and economic burden. Despite its prevalence and the availability of treatments, migraine is an underdiagnosed and undertreated disease, and there remains a need for novel oral preventive treatments with improved benefit-risk profiles. Current oral preventive treatments are often ineffective or poorly tolerated. As a result, a substantial number of patients discontinue or cycle through treatments without adequately reducing migraine frequency or severity. This leads to increased disability, preventing those with migraine from performing daily activities and significantly impacting their quality of life. There is a need for new treatments for migraine with improved benefit-risk profiles as compared to current standard of care.
Allergan, a leader in the Chronic Migraine space, markets BOTOX® (onabotulinumtoxinA) the first preventive treatment for adult Chronic Migraine patients since it was approved in 2010. Allergan is also advancing its migraine program with two investigational small molecule oral calcitonin gene-related peptide (CGRP) receptor antagonists, which are being developed for the treatment and prevention of migraine. Allergan’s CGRP receptor antagonists, ubrogepant in Phase 3 for the acute treatment of migraine and atogepant in Phase 2b/3 for the prevention of migraine, are expected to be the first oral CGRP receptor antagonists to market.
About Allergan
Allergan plc (NYSE: AGN), headquartered in Dublin, Ireland, is a bold, global pharmaceutical leader. Allergan is focused on developing, manufacturing and commercializing branded pharmaceutical, device, biologic, surgical and regenerative medicine products for patients around the world.
Allergan markets a portfolio of leading brands and best-in-class products for the central nervous system, eye care, medical aesthetics and dermatology, gastroenterology, women’s health, urology and anti-infective therapeutic categories.
Allergan is an industry leader in Open Science, a model of research and development, which defines our approach to identifying and developing game-changing ideas and innovation for better patient care. With this approach, Allergan has built one of the broadest development pipelines in the pharmaceutical industry.
Allergan’s success is powered by our global colleagues’ commitment to being Bold for Life. Together, we build bridges, power ideas, act fast and drive results for our customers and patients around the world by always doing what is right.
With commercial operations in approximately 100 countries, Allergan is committed to working with physicians, healthcare providers and patients to deliver innovative and meaningful treatments that help people around the world live longer, healthier lives every day.
For more information, visit Allergan’s website at www.Allergan.com.
Forward-Looking Statement
Statements contained in this press release that refer to future events or other non-historical facts are forward-looking statements that reflect Allergan’s current perspective on existing trends and information as of the date of this release. Actual results may differ materially from Allergan’s current expectations depending upon a number of factors affecting Allergan’s business. These factors include, among others, the difficulty of predicting the timing or outcome of FDA approvals or actions, if any; the impact of competitive products and pricing; market acceptance of and continued demand for Allergan’s products; the impact of uncertainty around timing of generic entry related to key products, including RESTASIS®, on our financial results; uncertainty associated with financial projections, projected cost reductions, projected synergies, restructurings, increased costs, and adverse tax consequences; difficulties or delays in manufacturing; and other risks and uncertainties detailed in Allergan’s periodic public filings with the Securities and Exchange Commission, including but not limited to Allergan’s Annual Report on Form 10-K for the year ended December 31, 2017 and Allergan’s Quarterly Report on Form 10-Q for the period ended March 31, 2018. Except as expressly required by law, Allergan disclaims any intent or obligation to update these forward-looking statements.
SOURCE Allergan plc
Posted: June 2018
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