Date: 2016-06-08
Type of information: Results
phase: 2
Announcement: results
Company: Amgen (USA - CA) Novartis (Switzerland)
Product: AMG 334 (erenumab)
Action
mechanism: monoclonal antibody. AMG 334 is a fully human monoclonal antibody under investigation for the prevention of migraine. AMG 334 inhibits Calcitonin-Gene-Related-Peptide (CGRP) by targeting its receptor, rather than CGRP itself, which is believed to transmit signals that can cause incapacitating pain. AMG 334 is currently under investigation in several large global, randomized, double-blind, placebo-controlled studies to evaluate its safety and efficacy in migraine prevention. In August 2015, Novartis entered into a global collaboration with Amgen to commercialize and develop new treatments in the field of Alzheimer's disease and migraine, including AMG 334 (currently in phase III studies for episodic migraine and a phase II study for chronic migraine) and AMG 301 (currently in a phase I study for migraine).
Disease: prevention of episodic migraine
Therapeutic area: CNS diseases
Country: Canada, Czech Republic, Denmark, Finland, Germany, Norway, Poland, Sweden, UK, USA
Trial
details: This phase 2, randomized, double-blind, placebo-controlled study evaluates the efficacy and safety of AMG 334 in migraine prevention (NCT01952574). The 20120295 study is a global phase II, randomized, 12-week, double-blind, placebo-controlled study evaluating the efficacy and safety of AMG 334 in chronic migraine prevention. In the study, 667 patients were randomized to receive once-monthly subcutaneous placebo or AMG 334 (70mg or 140mg) in a 3:2:2 ratio respectively.The primary outcome measure was the change in monthly migraine days 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 9 and 12). Secondary study endpoints included proportion of patients with at least a 50% reduction from baseline in monthly migraine days in the last four weeks of the 12-week treatment phase (50% responder rate), acute migraine-specific medication use days, cumulative hours of headache, and safety and tolerability.(NCT02066415)
Latest
news: * On June 8 2016, Novartis announced positive first results from the global phase II 20120295 study, investigating the efficacy and safety of AMG 334 (erenumab) in chronic migraine prevention. The study evaluated AMG 334 at two doses, 70mg and 140mg, administered subcutaneously once a month, with both doses meeting the study's primary endpoint of a statistically significant reduction in the number of monthly migraine days versus placebo. Overall, patients had a mean baseline of 18 migraine days per month. Patients randomized to the 70mg and 140mg dose groups experienced a mean 6.6-day reduction from baseline in monthly migraine days in both groups. The results were statistically significant compared with 4.2 days observed in the placebo group. The safety and tolerability profile of AMG 334 was similar to placebo in both treatment groups. No adverse event was reported in greater than five percent of patients treated with AMG 334; the most commonly reported adverse events included injection site pain, infection of the upper respiratory tract and nausea. * On June 19, 2015, Amgen announced positive interim results from its open-label extension of the global Phase 2, double-blind, placebo-controlled study evaluating the safety and efficacy of AMG 334 for the prevention of episodic migraine. Patients who entered the open-label phase received AMG 334 70 mg monthly and experienced a sustained reduction in monthly migraine days at week 52. The data were presented at the 57th Annual Scientific Meeting of the American Headache Society (AHS) on June 19, 2015, in Washington, D.C. At one year, patients receiving AMG 334 70 mg experienced an average of a -4.9-day reduction from a baseline of 8.7 mean monthly migraine days, regardless of treatment received during the blinded phase. The 50 percent responder rate (greater than 50 percent reduction in monthly migraine days) was 62 percent at 52 weeks. Additional responder rates were reported for the first time: at 52 weeks the 75 percent responder rate was 38 percent and the 100 percent responder rate was 19 percent. The open-label portion of the Phase 2 study included 383 patients. All patients received AMG 334 70 mg starting at week 12 for up to 256 weeks. Safety and tolerability were evaluated monthly and this interim analysis includes data up to week 52. Additional efficacy endpoints included the change in monthly migraine-specific medication use days and patient-reported outcomes using the Migraine Disability Assessment (MIDAS) questionnaire. Patients reported a nearly 50 percent reduction of monthly migraine-specific medication use days of -2 at 52 weeks, from a baseline of 4.3 days per month. In addition to clinical measures, patients self-reported the impact of headache and migraine on their daily activities. At one year, using the MIDAS tool, patients reported an improvement of approximately 12 days over the previous three months in their ability to function in work, home and social situations. According to the Migraine Research Foundation , migraine costs American employers more than $13 billion each year as a result of 113 million lost work days. The safety and tolerability profile during the open-label phase was similar to that observed in the blinded phase of the study. The most commonly reported adverse events included fatigue, influenza, nasopharyngitis, arthralgia and back pain. No Grade 4 or 5 adverse events were reported. Serious adverse events were reported in 13 patients, one of which was deemed treatment-related. Less than 5 percent of patients discontinued the study during the open-label phase due to adverse events. * On May 15, 2015, Amgen announced the first results from its global Phase 2, double-blind, placebo-controlled study evaluating the efficacy and safety of AMG 334 for the prevention of episodic migraine. The study met its primary endpoint of reducing monthly mean migraine days compared with placebo. The data were presented at the 17th Congress of the International Headache Society (IHC 2015) in Valencia, Spain. In the trial, 483 patients were randomized to subcutaneous monthly placebo or AMG 334 (7 mg, 21 mg or 70 mg) in a 3:2:2:2 ratio, respectively. Patients had a mean baseline of 8.7 migraine days per month. The primary endpoint was the change from baseline in monthly migraine days at week 12. Patients randomized to the 70 mg dose group observed a statistically significant 3.4-day reduction in monthly migraine days compared with 2.28 days observed in the placebo group (p=0.021). Secondary study endpoints included a 50 percent responder rate, monthly migraine attacks, and safety and tolerability. Key exploratory endpoints included change in monthly headache days and change in monthly acute migraine-specific medication use days. AMG 334 demonstrated a statistically significant increase in the 50 percent responder rate compared with placebo (47 percent vs. 30 percent, respectively). Furthermore, reductions in monthly headache days (-3.54 vs. -2.39) and monthly migraine-specific medication use days (-1.64 vs. -.69) were also statistically significant in patients taking the 70 mg AMG 334 dose compared with placebo, respectively. The dose tolerability profile of AMG 334 was similar to placebo across all dosing groups. The most commonly reported adverse events included fatigue, influenza, nasopharyngitis, arthralgia and back pain. No Grade 4 or 5 adverse events were reported.
Additional analyses of these data are ongoing and are expected to be submitted to a future medical meeting and for publication. Novartis and Amgen are also evaluating AMG 334 in two ongoing phase III studies in episodic migraine, with initial data from these studies expected later this year.
