Amgen has announced new data in patients with high unmet need, providing further evidence of the efficacy of Aimovig (erenumab) for migraine prevention. Aimovig is the first and only investigational biologic product specifically designed to prevent migraine by blocking the calcitonin gene-related peptide (CGRP) receptor, which is associated in migraine activation.
The data include a pre-planned sub-analysis from the pivotal Phase 2 chronic migraine study, demonstrating that Aimovig reduced the number of monthly migraine days (MMDs) in patients who have failed previous preventive therapies. Additionally, results from a dedicated study in patients with stable angina adds further support to the safety profile of Aimovig. These results will be presented at the 18th Congress of the International Headache Society in Vancouver, Canada.
"Data from our robust clinical development program continue to show that Aimovig has demonstrated efficacy in a broad range of patients, including hard-to-treat chronic migraine sufferers who have previously tried and failed other preventive therapies," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "Separately, new results from a treadmill safety study showed no adverse cardiovascular effect compared to placebo in patients with coronary artery disease and stable angina, which complements our extensive safety database and ongoing long-term extension studies of Aimovig for migraine prevention."
Studies have shown that up to 80 percent of people with migraine discontinue preventive treatment within one year. In a pre-specified sub-analysis from the Phase 2 study, Aimovig showed benefits for people with chronic migraine who have previously tried and failed preventive treatments. At the end of the 12-week study, patients who had failed two or more prior preventive treatments experienced a reduction of 7.0 days and 5.4 days in the Aimovig 140 mg and 70 mg, respectively, compared to placebo reduction of 2.7 days (p<0.001). Furthermore, in the Aimovig treated arms, the odds of cutting migraine days in at least half was three-to-four fold higher than in the placebo arm (140 mg: 41.3 percent, 70 mg: 35.6 per cent, placebo: 14.2 per cent (p<0.001 for both doses versus placebo).
The safety profile of Aimovig was similar to placebo across both treatment arms in the phase 2 study. No adverse event was reported in greater than five percent of patients treated with Aimovig; the most common adverse events were injection site pain, upper respiratory tract infection and nausea.
Aimovig was tested in a group of patients with stable angina due to coronary artery disease. A treadmill "stress test" is often used to gauge how well a patient's heart can handle exercise. The study met it primary endpoint of noninferiority, showing no difference in exercise time among participants receiving Aimovig or placebo. The treatment difference in mean change from baseline in exercise time was -11.0 seconds (90 per cent confidence interval -44.9, 22.9). In addition, no significant differences were seen between the two groups in time to onset of angina or time to onset of electrocardiogram change consistent with onset of myocardial ischemia. Adverse events were reported in 27 percent of patients receiving Aimovig and in 32 per cent of patients receiving placebo. The most frequent treatment-emergent adverse events (reported in >2 per cent of patients) were headache (4.5 per cent) and viral upper respiratory infection (4.5 per cent) in the Aimovig group, and were hypotension (4.5 per cent), influenza (4.5 percent) and viral infection (4.5 percent) in the placebo group.
"While the community has watched the next generation of migraine preventives with excitement, because CGRP has a vasodilatory effect, there have been questions about a potential impact on cardiovascular function especially in at-risk populations," said Amaal J. Starling, M.D., assistant professor of neurology at the Mayo Clinic in Scottsdale, Ariz., and a study co-author. "The results of this study provide some evidence that CGRP receptor inhibition did not aggravate myocardial ischemia in at-risk population of patients with stable angina compared to placebo and contribute to the growing body of evidence supporting the safety profile of Aimovig."
These results are consistent with the known safety profile of Aimovig, as seen across the broad clinical program involving more than 2,600 migraine patients.
Regulatory submissions for Aimovig have been filed in the United States (US) and Europe. The US Food and Drug Administration (FDA) has set a Prescription Drug User Fee Act (PDUFA) target action date of May 17, 2018. If approved, Novartis and Amgen 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.
The 20120295 study is a global Phase 2, randomized, 12-week, double-blind, placebo-controlled study evaluating the safety and efficacy of Aimovig in chronic migraine prevention. In the study, 667 patients were randomized to receive once-monthly subcutaneous placebo or Aimovig (70 mg or 140 mg) in a 3:2:2 ratio, respectively. The primary endpoint was change in MMDs from baseline to the last four weeks of the 12-week treatment phase in patients with chronic migraine (the number of migraine days between weeks nine and 12). Secondary study endpoints included reduction of at least 50 percent from baseline in monthly migraine days, change from baseline in monthly acute migraine-specific medication days and change from baseline in cumulative monthly headache hours.
The 20140254 study is a double-blind, placebo-controlled cardiovascular safety study in patients with stable angina due to documented coronary artery disease. Patients were randomized 1:1 to a single intravenous infusion of Aimovig 140 mg or placebo stratified by baseline treadmill exercise test (TET) (<7 minutes or =7 minutes) defined as the average TET of two qualifying exercise tolerance tests (ETTs) performed during screening. Following study drug administration on Day 1, a post-administration ETT was conducted. The primary endpoint was the change from baseline in exercise duration as measured by TET with a non-inferiority margin of -90 seconds. Secondary efficacy endpoints included time to onset of =1 mm ST-segment depression and time to onset of exercise-induced angina during the ETT. Safety follow-up visits occurred every 2-4 weeks for 12 weeks. Adverse events were reported by 14 percent of Aimovig-treated patients and by 27 percent of placebo patients and were consistent with the known safety profile of erenumab.