Amgen announced full results from the phase 3b LIBERTY trial of Aimovig (erenumab) in episodic migraine patients who had previously failed two to four preventive treatments, due to lack of efficacy or to intolerable side effects.
The data, which will be presented at the 70th Annual Meeting of the American Academy of Neurology (AAN) in Los Angeles, show the potential of Aimovig as an effective preventive treatment option for these patients, who have tried several treatment options without gaining relief. Aimovig is the only investigational fully human monoclonal antibody under regulatory review that was designed to selectively block the calcitonin gene-related peptide (CGRP) receptor, which plays a critical role in migraine activation. LIBERTY is the first study to investigate a treatment targeting the CGRP pathway specifically in this challenging patient population.
In LIBERTY, 246 patients who had experienced two to four previous preventive treatment failures were randomized to receive monthly subcutaneous injections of either Aimovig 140 mg or placebo for 12 weeks. Patients taking Aimovig had nearly three-fold higher odds of having their migraine days cut by at least 50 per cent, with more than twice as many patients taking Aimovig achieving this reduction compared to placebo (weeks 9-12: 30.3 per cent with Aimovig, 13.7 per cent with placebo, p<0.002, odds ratio 2.73).
“We are encouraged by these new findings, which add to the growing body of clinical evidence supporting potential use of Aimovig across a broad spectrum of patients with migraine, all of whom live with what is considered one of the most disabling diseases,” said Sean E. Harper, M.D., executive vice president of research and development at Amgen. “These data support the overall efficacy and safety profile we have seen consistently during extensive clinical study of Aimovig, and speak to its potential to help fill treatment gaps in more difficult patient populations whose migraine has not been adequately managed with current therapies.”
In the study, patients taking Aimovig also had statistically significant and clinically meaningful improvements from baseline compared to placebo across all secondary endpoints: Reduction in monthly migraine days; Decrease in monthly acute migraine-specific drug use; 75 per cent or greater reduction in monthly migraine days; 100 per cent reduction in monthly migraine days; Improved physical functioning and ability to complete everyday activities as measured by the Migraine Physical Function Impact Diary (MPFID).
Over 97 per cent of Aimovig patients completed the double-blind phase of the LIBERTY study. There were no adverse events leading to discontinuation of treatment in the Aimovig group, while 0.8 per cent of those in the placebo group experienced adverse events leading to discontinuation of treatment.
“The LIBERTY study distinctively demonstrates the ability of an anti-CGRP receptor antibody to significantly reduce migraine frequency and its associated burden in patients who could not find the relief they need from currently available preventive treatment options,” said professor Uwe Reuter, managing medical director at Charité Universitätsmedizin in Berlin. “These compelling data offer new hope of fewer migraine days to those people with migraine who may have cycled through current standard of care unsuccessfully for years due to lack of efficacy and tolerability.”
The long-term open label extension phase of the study is ongoing. LIBERTY contributes to an extensive body of evidence, across the spectrum of migraine, in support of the efficacy, safety and tolerability profile of Aimovig. Aimovig has been studied in four placebo-controlled phase 2 and phase 3 clinical studies involving more than 3,000 patients and continues to be studied in an ongoing open-label extension for up to five years in duration.
The US Food and Drug Administration (FDA) has set a Prescription Drug User Fee Act (PDUFA) target action date of May 17, 2018, for Aimovig and the European Medicines Agency has validated the Marketing Authorization Application (MAA) for Aimovig. If approved, it will be administered once-monthly using a self-injection device. If approved, Amgen and Novartis will co-commercialize Aimovig in the US. Amgen has exclusive commercialization rights to the drug in Japan, and Novartis has exclusive rights to commercialize in rest of world.
LIBERTY (NCT03096834) is a phase 3b, multicenter, randomized 12-week, double-blind, placebo-controlled study evaluating the safety and efficacy of Aimovig in patients with episodic migraine (defined in the trial as four to 14 migraine days per month at baseline) who have failed up to four prior preventive treatments for migraine. In the study, 246 participants with episodic migraine who had two to four previous treatment failures were randomized to receive Aimovig 140 mg or placebo during the 12-week double-blind treatment phase. The primary endpoint was the percentage of patients with at least a 50 per cent reduction of monthly migraine days from baseline over the last four weeks of the double-blind treatment phase of the study (weeks 9-12).1 The study includes an ongoing 52-week open-label extension study.
Secondary endpoints assessed during the same time period included: change from baseline in monthly migraine days, change from baseline in the number of monthly acute migraine-specific medication treatment days and change from baseline in the Migraine Physical Function Impact Diary (MPFID) physical impairment and impact on everyday activities domain scores. The MPFID is a scale developed to measure these two domains. The scale has been validated in line with FDA Patient Reported Outcomes Guidance.2 Percentages of patients with a 75 per cent response rate and 100 per cent response rate to Aimovig were also assessed as secondary endpoints.
Aimovig is the only investigational treatment under regulatory review that was specifically designed to prevent migraine by blocking the CGRP receptor, which is associated with migraine activation. Aimovig has been studied in several large global, randomized, double-blind, placebo-controlled studies to assess its safety and efficacy in migraine prevention. More than 3,000 patients have participated in the Aimovig clinical programme across four placebo-controlled phase 2 and phase 3 clinical studies and their open-label extensions.
In August 2015, Amgen entered into a global collaboration with Novartis to develop and commercialize pioneering treatments in the field of migraine and Alzheimer's disease. The collaboration focuses on investigational Amgen drugs in the migraine field, including Aimovig (Biologics License Application submitted to FDA in May 2017) and AMG 301 (currently in phase 2 development). In April 2017, the collaboration was expanded to include co-commercialization of Aimovig in the US. For the migraine programmes, Amgen retains exclusive commercialization rights in the US (other than for Aimovig as described above) and Japan, and Novartis has exclusive commercialization rights in Europe, Canada and rest of world.