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Allergan Announces Second Positive Phase 3 Clinical Trial for Ubrogepant -- an Oral CGRP Receptor Antagonist for the Acute Treatment of Migraine

Update: Ubrelvy (ubrogepant) Now FDA Approved - December 23, 2019

DUBLIN, April 27, 2018 /PRNewswire/ -- Allergan plc, (NYSE: AGN), a leading global pharmaceutical company today announced positive results from ACHIEVE II (UBR-MD-02), the second of two pivotal Phase 3 clinical trials evaluating the efficacy, safety and tolerability of orally administered ubrogepant 25 mg and ubrogepant 50 mg compared to placebo in a single migraine attack in adults. Allergan anticipates filing of a New Drug Application (NDA) to the FDA in 2019.

The ACHIEVE II study included 1,686 U.S. adult patients randomized (1:1:1) to placebo, ubrogepant 25 mg and 50 mg respectively, to treat a single migraine attack of moderate-to-severe headache intensity.

In the modified ITT (mITT) population of 1355 patients, both doses showed a statistically significant greater percentage of ubrogepant patients achieving pain freedom at 2 hours after the initial dose as compared to placebo patients (25 mg vs placebo, p=0.0285, 50 mg vs placebo, p=0.0129) and the 50 mg dose demonstrated a statistically significant greater percentage of ubrogepant patients achieving absence of the most bothersome migraine-associated symptom at 2 hours after the initial dose as compared to placebo patients (50 mg vs placebo, p=0.0129). The 25 mg dose demonstrated improvement in the percentage of ubrogepant patients achieving absence of the most bothersome migraine-associated symptom at 2 hours after the initial dose as compared to placebo patients, however failed to demonstrate statistical significance (25 mg vs placebo, p=0.0711).

The 50 mg dose of ubrogepant also showed a statistically significant greater percentage of patients achieving pain relief at 2 hours, sustained pain relief from 2-24 hours, and sustained pain freedom from 2-24 hours after the initial dose as compared to placebo (50 mg vs placebo, p=0.0129 for each of these endpoints). In addition, ubrogepant 50 mg also showed a statistically significant greater percentage of patients achieving absence of photophobia (p= 0.0167) and phonophobia (p= 0.0440) at 2 hours after the initial dose as compared to placebo. Ubrogepant 25 mg compared to placebo failed to demonstrate statistical significance in these endpoints.

"We are pleased to share these positive results from ACHIEVE II, our second Phase 3 study supporting the efficacy, safety, and tolerability of 50 mg ubrogepant. The consistency in response between both ACHIEVE I and ACHIEVE II provides further evidence that ubrogepant, an oral calcitonin gene-related peptide (CGRP) receptor antagonist, offers a promising opportunity for the acute treatment of migraine", said David Nicholson, Chief Research and Development Officer, Allergan. "Allergan is committed to addressing unmet patient needs through product innovation and has identified a clear need in the migraine marketplace."

In ACHIEVE II, ubrogepant was well tolerated and demonstrated a safety profile similar to placebo. There was no signal of hepatotoxicity for ubrogepant. The most common adverse events were nausea and dizziness, neither of which was reported with a frequency >2.5%. In terms of hepatic safety within 30 days of dosing, there were 4 cases (1 in placebo and 3 in ubrogepant arms) with aminotransferase (ALT or AST) elevations greater than 3 times (but not higher than 5 times) the upper limit of normal (ULN). Each of these 4 cases were adjudicated by a blinded panel of liver experts and none were noted by the liver safety adjudication board to have a probable relationship to ubrogepant. Of these 4 cases, one case was noted within 7 days of drug administration (attributed to exercise-induced rhabdomyolysis, on 50 mg ubrogepant and again, noted by the liver safety adjudication board to not have a probable relationship to ubrogepant). There were no cases of Hy's Law.

"Given the prevalence of migraine and significant disability that many patients face, ubrogepant may provide a new option for those having tolerability issues with current migraine-specific treatments." said Dr. Stephen Silberstein, Director, Headache Center, Thomas Jefferson University. "In addition, a need exists for treatments when there is a contraindication to migraine-specific medications. Results from ACHIEVE II will lead to a new treatment that will improve the lives of patients."

Additional results from this study are anticipated to be released at upcoming scientific meetings throughout 2018.

About ACHIEVE II Study

The ACHIEVE II trial is a Phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy, safety, and tolerability of 2 doses of ubrogepant (25 mg and 50 mg) compared to placebo for the treatment of a single migraine attack. The modified ITT population included 1355 adult patients 18-75 years of age with a history of migraine (with or without aura) randomized (1:1:1) to placebo, ubrogepant 25 mg, or ubrogepant 50 mg to treat a single migraine attack of moderate or severe headache pain intensity at home. The co-primary efficacy parameters were pain freedom (PF) at 2 hours after the initial dose (defined as a reduction in headache severity from moderate/severe at baseline to no pain at 2 hours after the initial dose) and absence of the most bothersome migraine-associated symptom (photophobia, phonophobia or nausea) at 2 hours after the initial dose.

About Ubrogepant

Ubrogepant is a novel, highly potent, orally-administered CGRP receptor antagonist in development for the acute treatment of migraine. CGRP and its receptors are expressed in regions of the nervous system associated with migraine pathophysiology. CGRP receptor antagonism is a novel mechanism of action for the acute treatment of migraine that clearly differs from the mechanisms of currently available triptans (serotonin 1B/1D agonists) and opioids.

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. The current standards of care in the acute treatment of migraine are not optimal for many patients due to partial effectiveness, poor tolerability, or contraindications. As a consequence, patients may experience repeated, uncontrolled attacks leading to medication overuse and increased risk of migraine disease progression. 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 and only FDA-approved, 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 III for the acute treatment of migraine and atogepant in Phase IIB 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. Except as expressly required by law, Allergan disclaims any intent or obligation to update these forward-looking statements.

SOURCE Allergan plc

Posted: April 2018

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