Allergan Announces Positive Phase 3 ACHIEVE II Trial Results for Ubrogepant Published in The Journal of the American Medical Association
-- Pivotal Phase 3 clinical trial reinforced efficacy, safety and tolerability of ubrogepant, an orally-administered CGRP receptor antagonist (gepant) --
-- Acute treatment of migraine with ubrogepant compared with placebo led to significantly greater rates of pain freedom at two hours with both the 50 mg and 25 mg doses, and freedom from the most bothersome migraine-associated symptom at two hours with the 50 mg dose --
-- FDA action on New Drug Application (NDA) expected in December 2019 for ubrogepant, potentially making it the first oral CGRP to address unmet patient needs in acute treatment of migraine and the first FDA-approved gepant --
DUBLIN, Nov. 19, 2019 /PRNewswire/ -- Allergan plc (NYSE: AGN) today announced that positive results from ACHIEVE II (UBR-MD-02), a pivotal Phase 3 clinical trial evaluating the efficacy, safety and tolerability of ubrogepant, have been published in the November 19th issue of The Journal of the American Medical Association (JAMA). These data reinforced that acute treatment of migraine with ubrogepant compared with placebo led to significantly greater rates of pain freedom at two hours with both the 50 mg and 25 mg doses, and freedom from the most bothersome migraine-associated symptom at two hours with the 50 mg dose. If approved, ubrogepant would potentially be the first FDA-approved small molecule, oral calcitonin gene-related peptide (CGRP) receptor antagonist (gepant) for the acute treatment of migraine.
"Migraine is the second leading cause of disability, and we need new acute treatments that are efficacious, safe, and tolerable," said Richard B. Lipton, M.D., Lead Author, Professor and Vice Chair of Neurology at the Albert Einstein College of Medicine and Montefiore Health System, Director of the Montefiore Headache Center. "Having ubrogepant as a potential new medication for the acute treatment of migraine will provide much-needed innovation for a disease that causes lost time for millions of people." Dr. Lipton is also a paid consultant for Allergan, the trial sponsor.
The ACHIEVE II trial evaluated ubrogepant 50 mg and 25 mg, compared with placebo, across a wide range of clinical endpoints, including the co-primary endpoints of pain freedom (no pain) and freedom from the most bothersome migraine-associated symptom at two hours post-initial dose. For the two co-primary endpoints, ubrogepant 50 mg and 25 mg showed statistically significant higher response rates for pain freedom at two hours (21.8% for 50 mg, 20.7% for 25 mg and 14.3% for placebo), and the 50 mg dose demonstrated statistically significant higher response rates for the freedom from the most bothersome migraine-associated symptom at two hours (38.9% for 50 mg and 27.4% for placebo). Additionally, ubrogepant 50 mg was statistically superior to placebo in the absence of light sensitivity (43.8% for 50 mg and 35.5% for placebo) and sound sensitivity (54.1% for 50 mg and 46.3% for placebo).
Ubrogepant studies show that both the 50 mg and 25 mg doses were well tolerated with an adverse event profile similar to placebo. The most common adverse reaction during the single attack studies (occurring with an incidence greater than 2 percent and at least twice the rate of placebo) was nausea (incidence 2-4%). In a year-long extension study, the most common treatment-related adverse event was also nausea, with an incidence <2 percent.
"I have been living with migraine attacks for most of my life, but unfortunately, I can't tolerate existing prescription treatments when I start having pain," said Anna Williams, migraine patient. "We really need new treatments, which is why I am so excited to see new research published in a prestigious medical journal about a medication that may provide what patients need."
Triptans are the most popular acute treatment for migraine representing 70 percent of prescriptions. However, for people living with migraine disease, approximately 20 percent of individuals have multiple cardiovascular (CV) risk factors, and because triptans restrict blood vessels, they may not be appropriate for these migraine patients. And for those who take triptans, as many as 30 percent may not sufficiently respond or may experience side effects. In the ACHIEVE II trial, approximately 11 percent of participants had moderate to severe CV risk factors, and 23 percent of participants previously had an insufficient response to triptans.
"If approved, ubrogepant will provide a new and different acute treatment option for patients suffering the debilitating pain and other symptoms of migraine. Allergan has a long history of developing migraine medications and remains committed to continued innovation of new treatments," said Mitchell Mathis, M.D., VP, Chief Medical Officer, Central Nervous System at Allergan. "Ubrogepant is a completely new approach to the acute treatment of migraine. This would expand Allergan's migraine portfolio that includes BOTOX®, the first FDA-approved, preventive treatment for adults with chronic migraine. We are also continuing to advance the Phase 3 clinical program for atogepant, our second orally-administered gepant specifically for migraine prevention. We believe in having multiple treatment options available because we know not every patient will respond to every medication. We believe that patients should have open access to all new treatments for migraine."
About ACHIEVE II (UBR-MD-02) Trial The ACHIEVE II trial is a Phase 3, multicenter, double-blind, parallel-group study evaluating the efficacy, safety, and tolerability of ubrogepant (50 mg and 25 mg) compared to placebo for the acute treatment of a single migraine attack of moderate or severe headache pain intensity at home. In this pivotal trial, 1,355 adult patients (18-75 years of age) with a history of migraine (with or without aura) were randomized (1:1:1) to placebo, ubrogepant 25 mg, or ubrogepant 50 mg. The co-primary efficacy parameters were pain freedom (no pain) at two hours after the initial dose and absence of 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 at the time of 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 2 hours, sustained pain relief from 2-24 hours, and sustained pain freedom from 2-24 hours, among others. Adverse events were collected and evaluated 48 hours after the initial and optional second dose of trial treatment, as well as within 30 days after administration of any dose.
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 agonists), opioids and ergots.
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; these symptoms are often debilitating. 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.
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