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Allergan Announces Positive Phase 3 ACHIEVE I Trial Results for Ubrogepant Published in The New England Journal of Medicine

-- Published data from a second robust Phase 3 clinical trial demonstrated efficacy, safety and tolerability of ubrogepant, an orally-administered CGRP receptor antagonist (gepant) --

-- Compared to placebo, ubrogepant 50 mg and 100 mg doses led to significantly greater rates of pain freedom and freedom from the most bothersome migraine-associated symptom at two hours, a new, more stringent FDA standard in the acute treatment of migraine --

-- Ubrogepant 50 mg and 100 mg also met the secondary efficacy endpoint demonstrating clinically significant pain relief at two hours in the majority of patients studied versus placebo, a primary endpoint used in the studies of older migraine treatments, such as triptans --

-- FDA action on New Drug Application (NDA) expected in December 2019 for ubrogepant, which would make it the first oral CGRP blocker (gepant) to address unmet patient needs in acute treatment of migraine --

DUBLIN, Dec. 4, 2019 /PRNewswire/ -- Allergan plc (NYSE: AGN) today announced that positive results from ACHIEVE I (UBR-MD-01), a robust Phase 3 clinical trial evaluating the efficacy, safety and tolerability of ubrogepant, have been published in the December 5th issue of The New England Journal of Medicine (NEJM). The data from this second published pivotal trial reinforced that the acute treatment of migraine with ubrogepant, compared with placebo, led to significantly greater rates of pain freedom and freedom from the most bothersome migraine-associated symptom at two hours with both the 50 mg and 100 mg doses. If FDA-approved, ubrogepant would be the first available and approved small molecule, oral calcitonin gene-related peptide (CGRP) receptor antagonist (gepant) for the acute treatment of migraine.

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"The findings from the ACHIEVE I trial are particularly meaningful for primary care physicians who are first-line in migraine management and need treatment options that are safe and effective to treat debilitating migraine symptoms," said Susan Hutchinson, MD, Family Practice Headache Specialist and Founder of Orange County Migraine & Headache Center and paid consultant for Allergan. "With limited migraine-specific acute treatment options on the market, the approval of ubrogepant would provide healthcare providers and patients a much-needed new treatment option with a favorable side-effect profile that can be taken on-demand to effectively treat a migraine attack."

The ACHIEVE I trial evaluated ubrogepant 50 mg and 100 mg, compared with placebo, across a wide range of endpoints, including more stringent FDA guidelines established in 2018 for the acute treatment of migraine: meeting both co-primary endpoints of pain freedom (no pain at all) and freedom from the most bothersome of three non-headache migraine-associated symptoms (no sensitivity to light, no sensitivity to sound, or no nausea at all) at two hours post initial dose. For the two co-primary endpoints, ubrogepant 50 mg and 100 mg showed statistically significant higher response rates for pain freedom at two hours (11.8% for placebo, 19.2% for 50 mg, 21.2% for 100 mg) and freedom from the most bothersome migraine-associated symptom at two hours (27.8% for placebo, 38.6% for 50 mg, 37.7% for 100 mg).

"Based on the recently published ACHIEVE I and ACHIEVE II data, I am confident that ubrogepant, with its novel mechanism of action as a gepant, will make a difference for people with migraine and unmet needs for acute treatment," said Richard B. Lipton, M.D., Author of ACHIEVE I and Lead Author of ACHIEVE II, Professor and Vice Chair of Neurology at the Albert Einstein College of Medicine and Montefiore Health System, Director of the Montefiore Headache Center. "The favorable safety and tolerability profile, as well as the efficacy data, for ubrogepant are particularly important as we consider new treatment options for people living with migraine." Dr. Lipton is also a paid consultant for Allergan, the trial sponsor.

Both doses of ubrogepant at 50 mg and 100 mg demonstrated significant improvement compared with placebo for a secondary efficacy endpoint of pain relief at two hours (49.1% for placebo, 60.7% for 50 mg, 61.4% for 100 mg). Pain relief was defined as the reduction in headache severity from moderate to severe pain to mild or no pain at two hours after initial doses. This secondary endpoint is most similar to the primary endpoint that older migraine treatments like triptans demonstrated for FDA approval. Additionally, both doses of ubrogepant were statistically superior to placebo in sustained pain relief from two to 24 hours (20.8% for placebo, 36.3% for 50 mg, 38.0% for 100 mg).

Both the 50 mg and 100 mg doses of ubrogepant were well tolerated with an adverse event profile similar to placebo. There were no serious adverse events. Nausea was the most common adverse event, reported at 1.6% for placebo, 1.7% for 50 mg, 4.1% for 100 mg. Rates of all treatment-emergent adverse events were also similar to placebo (12.8% in placebo, 9.4% for 50 mg, 16.3% in 100mg).

"I have been living with migraine attacks for more than 20 years, but unfortunately I do not have any tolerable prescription treatment options to take when I start having pain," said Anna Williams, migraine patient. "I am hopeful for new treatment options that will eliminate my debilitating pain along with other migraine symptoms."

Triptans are by far the most commonly used prescription medications for migraine, representing 73% of prescriptions within the acute treatment market. However, for people living with migraine, 67% report delaying or avoiding taking their prescription medication when a migraine attack occurs, often because of the adverse events they experience from the treatment. In addition, approximately 20% people with migraine have cardiovascular (CV) disease, and because triptans constrict blood vessels, they may be contraindicated in this patient population. For those who take triptans, as many as 30% may not sufficiently respond or may experience side effects.

"We are pleased to see the results from our pivotal Phase 3 trial published in The New England Journal of Medicine," said Mitchell Mathis, M.D., VP, Chief Medical Officer, Central Nervous System. "With the ACHIEVE II trial results recently published in The Journal of the American Medical Association, the recognition from these two prestigious medical journals underscores the significance of ubrogepant as a promising oral option for the acute treatment of migraine. We are proud of the research and science that have brought us to this point and look forward to continuing innovation in the pursuit of migraine freedom."

The full NEJM article is available at http://bit.ly/2qWuI4R

About ACHIEVE I (UBR-MD-01) Study
The ACHIEVE I trial is a Phase 3, multicenter, double-blind, parallel-group, study evaluating the efficacy, safety, and tolerability of ubrogepant (50 mg and 100 mg) compared to placebo for the acute treatment of a single migraine attack of moderate or severe headache pain intensity. In this pivotal trial, 1,672 adult participants (18-75 years of age) with a history of migraine (with or without aura) were randomized (1:1:1) to placebo, ubrogepant 50 mg, or ubrogepant 100 mg. The co-primary efficacy parameters were pain freedom (no pain) at two hours after the initial dose and freedom from the most bothersome migraine-associated symptom at two hours after the initial dose. The most bothersome migraine-associated symptom could include photophobia, phonophobia, or nausea and was selected by the participant immediately prior to treating a qualifying migraine attack. Secondary efficacy endpoints also evaluated the clinical benefits of ubrogepant across a wide range of outcome measures, including pain relief at two hours, sustained pain relief from 2 to 24 hours, and sustained pain freedom from 2 to 24 hours, among others. Adverse events were collected and evaluated for 48 hours after the initial and optional second dose of trial treatment, as well as within 30 days after administration of any dose.

About ACHIEVE I (UBR-MD-01) and ACHIEVE II (UBR-MD-02)
ACHIEVE I and ACHIEVE II both tested the efficacy of ubrogepant to treat a single migraine attack. The protocols for the two trials were identical except for the doses of ubrogepant tested.  ACHIEVE I tested doses of 50 mg and 100 mg versus placebo, whereas ACHIEVE II tested doses of 25 mg and 50 mg versus placebo. 

About Ubrogepant
Ubrogepant is a novel, highly potent, orally-administered CGRP receptor antagonist (gepant), 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 completely new mechanism of action for the acute treatment of migraine compared to medications currently available, which include triptans (serotonin 1B/1D receptor agonists), opioids, ergots as well as over-the-counter medications, such ibuprofen and acetaminophen.

About Migraine  
Migraine is a chronic disease with episodic attacks defined by neurological symptoms such as headache pain, sensitivity to light and sound, and nausea. Migraine is highly prevalent, affecting approximately 31 million Americans, and is associated with significant disability leading to high personal, family, occupational, societal, and economic burden. Based on the current standard of care, there are still unmet needs for new acute treatments for migraine.

Allergan, a leader in the migraine space, markets BOTOX® (onabotulinumtoxinA), the first FDA-approved, preventive treatment for adult Chronic Migraine (approved 2010). Allergan is also advancing its migraine program with two investigational small molecule oral calcitonin gene-related peptide (CGRP) receptor antagonists (gepants), one of which is being developed for the acute treatment of migraine and one for the prevention of migraine. In addition to ubrogepant, which is expected to be the first FDA-approved gepant with a completely new approach for acute treatment of migraine, atogepant is currently in Phase 3 development for the prevention of migraine.

About Allergan MIND™ 
As part of Allergan's ongoing commitment to innovating and inspiring change in the migraine community, the company has established a migraine franchise, Allergan MIND™ (Migraine:  Innovation, Navigation, Discovery), to drive progress and unify its efforts as a worldwide leader in migraine. Allergan MIND™ represents the company's vision and mission to continue advancing science and improving the lives of people living with migraine with treatments, education and support in the pursuit of migraine freedom. This new migraine franchise serves as a center of excellence and catalyst for advancing the dialogue and treatment landscape in migraine, bringing together diverse stakeholders to rally around the latest insights and developments that will impact the future of migraine.

About Allergan plc
Allergan plc (NYSE: AGN), headquartered in Dublin, Ireland, is a global pharmaceutical leader 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 primarily focused on four key therapeutic areas including medical aesthetics, eye care, central nervous system and gastroenterology. As part of its approach to delivering innovation for better patient care, Allergan has built one of the broadest pharmaceutical and device research and development pipelines in the industry.

With colleagues and commercial operations located 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; risks associated with divestitures, acquisitions, mergers and joint ventures; risks related to impairments; uncertainty associated with financial projections, projected cost reductions, projected debt reduction, 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, 2018 and Allergan's Quarterly Report on Form 10-Q for the period ended September 30, 2019. Except as expressly required by law, Allergan disclaims any intent or obligation to update these forward-looking statements.

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