Erenumab

35809611000001100

New Medicines

Aimovig · Migraine prophylaxis

Information

Aimovig
New molecular entity
Novartis
Amgen

Development and Regulatory status

Launched
Launched
Launched
September 2018

Oct 18: 70mg soln for inj in prefilled pen, 1=£386.50 [27]


Sep 18: Launched in the UK [26].


Jul 18: Launched in US [25].


Jul 18: Novartis says it is working closely with all stakeholders to ensure eligible patients can start benefiting from this treatment as quickly as possible in the UK. A bespoke patient support programme and range of resources are also being developed in order to provide support to patients and healthcare professionals [24].


Jul 18: Approved in EU [24].


Jun 18: Official list price in the US confirmed at lower than expected $6,900 per year, prompting amendment to the original Institute for Clinical and Ecomonic Review report to endorse cost effectiveness of erenumab, but only for patients for whom other preventive treatments have failed [23].


May 18: recommended for EU approval by CHMP - full indication is "for prophylaxis of migraine in adults who have at least 4 migraine days per month”, and it is proposed that it be prescribed by physicians experienced in the diagnosis and treatment of migraine [22].


May 18: Erenumab approved in the US for the preventive treatment of migraine in adults [21]


Jul 17: FDA accepts biologics license application for erenumab (Aimovig) for prevention of migraine [17].


Jun 17: Filed in the EU [16].


May 17: Filed in the US [15].


Mar 17: Novartis intend to file in the EU during 2017 [13].


Jun 16: Amgen hopes to file for approval following the upcoming readout from a PIII trial in H2 2016, and secure an advantage of being first to market compared with rivals galcanezumab (Lilly), TEV-48125 (Teva) and ALD-403 (Alder). Even if Amgen is unable to identify an efficacy edge, it could still secure the advantage of being first to market. Amgen believes that together with the PIII episodic data, the PII chronic data could potentially support both chronic and episodic indications being granted, at least by some global regulators [8].


Dec 15: Novartis lists AMG-334 in their development pipeline, but do not state planned date of filing [7].


Aug 15: PIII studies in episodic migraine are underway, & PII study in chronic migraine is ongoing [4].

Category

Human monoclonal antibody that works by inhibiting the calcitonin gene-related peptide receptor believed to transmit signals that can cause incapacitating pain.
Numbers may be misleading, as many who experience migraine do not consult their GP, but migraine affects about 6% of men and 18% of women. In children it is more common in boys than in girls. The first attack is often in childhood and over 80% have had their first attack by the age of 30 [2].
Migraine prophylaxis
Subcutaneous

Further information

Yes
To be confirmed

Trial or other data

Oct 18: Results of PIIIb LIBERTY study (NCT03096834) published in The Lancet. RCT (n=246) found at week 12, 36 (30%) patients on erenumab had ≥50% reduction from baseline in mean number of monthly migraine days, compared with 17 (14%) in placebo group (OR 2.7 [95% CI 1.4 to 5.2]; p=0.002). Tolerability and safety profiles of erenumab and placebo were similar [28].


Oct 18: Alder, Lilly and Teva are all developing CGRP drugs. Alder and Lilly have both posted placebo-adjusted reductions in migraine days that are almost inseparable from the 1.1 days achieved by AMG 334. While the PIII data and real-world use could still uncover meaningful differences between the drugs, the only advantage AMG 334 looks to have is first-to-market status [9]. Aimovig (erenumab) is in a new class of drugs, and provides patients with a novel option for reducing number of days with migraine [21].


Apr 18: PIIIb LIBERTY trial meets primary endpoint. Results show 30.3% of erenumab treated patients had number of migraine days reduced by half compared to 13.7% of patients on placebo [20].


Dec 17: Aimovig™ (erenumab) PIII STRIVE data published in the New England Journal Of Medicine.[18,19]


Apr 17: Amgen releases the full set of data from the STRIVE and ARISE studies. The data from the two studies were not overwhelmingly positive, but clearly show that erenumab is better than placebo when it comes to reducing monthly migraine days and showed that the drug had excellent safety and tolerability. In STRIVE, for example, a 70-mg dose of the antibody reduced the number of days in a month with migraine attacks by 1.4 compared to placebo, with a 140-mg dose cutting this measure by 1.9 days. Overall, 60% of people on erenumab experienced a 50% or greater reduction in migraine days. Analysts suggest the reductions are comparable to those seen with eptinezumab in phase 2 but not quite as good as galcanezumab and TEV-48125 in mid-stage testing—with the obvious caveat that no definitive clinical comparison can be made in the absence of head-to-head trials. Phase 3 data on the other three CGRPs is due in the next 12-18 months [14].


FNov 16: Data from the STRIVE study shows erenumab achieved a significant reduction in the number of days patients experienced severe headaches. At enrolment patients were experiencing an average of around 8 days with migraines per month. Treatment with 70mg or 140mg of erenumab cut that by 3.2 and 3,7 days respectively, while those on placebo experienced a 1.8-day reduction [12].


Oct 16: Novartis initiated the PIII LIBERTY trial (EudraCT2016-002211-18) in Spain and Austria, with roll-out intended to other EU countries including the UK. It will evaluate the efficacy and safety of erenumab vs. placebo in patients who have failed 2 - 4 prophylactic treatments; primary outcome is achievement of at least 50% reduction from baseline in monthly migraine days during month three of the three month study. Estimated recruitment is 382 and estimated overall duration 2 years 2 months [10. 11].


Sep 16: Amgen and Novartis announc PIII data for AMG-334. In the PIII trial, 577 patients were randomized to receive placebo or a once-monthly injection of 70mg of AMG 334. Participants in the treatment arm experienced a statistically-significant fall in monthly migraine days as compared to the baseline, causing the study to hit its primary endpoint. Having experienced an average of eight migraine days a month going into the trial, subjects on AMG 334 had 2.9 fewer migraine days over the final four weeks of the 12-week clinical trial. The number of migraine days in the placebo arm fell by 1.8 over the same period, resulting in a placebo-adjusted reduction of 1.1 days. AMG 334 showed a similar safety profile to placebo [9].


Jun 16: Amgen and Novartis report that erenumab met the primary endpoint in a PII trial assessing efficacy in preventing chronic migraines. The 667 participants in the study received either one of two once-monthly injected doses of erenumab--70 mg or 140 mg--or a placebo. Following 12 weeks of treatment, Amgen assessed the change in monthly migraine days. Having experienced 18 migraine days a month at baseline, patients in the treatment arm reported having fewer than 12 days a month at the end of the trial; a 6.6-day reduction in the treatment cohort vs. a 4.2-day drop in the placebo arm [8].


Feb 16: Results of PII NCT01952574 (n=483) published in the Lancet. This study found that the mean monthly change in migraine days after 12 weeks was-3.4 for AMG-334 70mg vs. -2.3 with placebo (difference -1.1; 95%CI -2.1 to -0.2). Adverse events were reported in 54% in both the 70mg and placebo arms [6].


Dec 15: NCT02483585 (ARISE) & NCT02456740 (STRIVE) are two ongoing PIII studies in patients (540 & 852, respectively) with episodic migraine comparing efficacy of AMG-334 vs placebo in reducing no. of monthly migraine days. ARISE, which incorporates a 12-week double-blind period and a 28 week open label extension, is due to complete Oct 17. STRIVE, a 24-week study is due to complete in Feb 18 [5].


Jun 15: Amgen announce positive interim results from open-label extension PII trial (n=383). At one year, patients receiving AMG-334 experienced an average of 4.9-day reduction from baseline of 8.7 mean monthly migraine days, regardless of treatment received during the blinded phase. The 50% responder rate (greater than 50% reduction in monthly migraine days) was 62% at 52 weeks. The 75% responder rate was 38% at 52 weeks and the 100% responder rate was 19% at 52 weeks [3].


May 15: First data from a mid-stage trial assessing the fully human monoclonal antibody AMG 334 show the drug to be effective in preventing migraine. In the trial, 483 patients with a mean baseline of 8.7 migraine days per month were randomised to receive subcutaneous monthly placebo or AMG 334. Those taking the 70mg dose of the drug observed a statistically significant 3.4-day reduction in monthly migraine days compared with 2.28 days observed in control arm. AMG 334 also showed a significant increase in the 50% responder rate compared with placebo (47% versus 30%, respectively), while reductions in monthly headache days (-3.54 v. -2.39) and monthly migraine-specific medication use days (-1.64 vs -.69) were also recorded in the 70mg AMG 334 group. On the safety side, tolerability was similar to placebo across all doses tested, the most commonly reported adverse events being fatigue, influenza, nasopharyngitis, arthralgia and back pain. No serious side effects were observed [1]

Evidence based evaluations