Amgen/Novartis CGRP Inhibitor Migraine Data Underwhelm Ahead Of Phase III Apex
Executive Summary
Amgen Inc. and Novartis AG are busy shoring up the case for their CGRP inhibitor erenumab – which is in a race with three others to be the first on to the migraine market. Positive topline Phase II data with erenumab has been reported but analysts suggest they may not be as strong as those from its competitors. The four CGRP inhibitors are all in Phase III with late-stage data expected this year.
Amgen Inc. has reported positive top-line results from the global Phase II study of erenumab (also called AMG 334) in chronic migraine prevention. The study met its primary endpoint of change in monthly migraine days. The reduction was significant for both the 70 mg and 140 mg doses.
"These positive results are exciting because they add to the growing body of evidence supporting erenumab for the prevention of migraine. We look forward to Phase III episodic migraine data later this year," said Dr. Sean Harper, Amgen's R&D head.
Amgen traded certain ex-US rights to the calcitonin gene-related peptide (CGRP) inhibitor for the treatment of migraine last year in return for shared global rights to an early stage candidate for Alzheimer's disease from Novartis AG. (Also see "Amgen, Novartis Trade Rights For Migraine, Alzheimer's Drugs" - Scrip, 2 Sep, 2015.)
Trial Details
In the study, 667 patients were randomized to receive once-monthly subcutaneous placebo or erenumab (70 mg or 140 mg) in a 3:2:2 ratio, respectively. At baseline, patients enrolled in this study were experiencing approximately 18 migraine days per month.
The primary endpoint was change in monthly migraine days from baseline to the last four weeks of the 12-week treatment phase in patients with chronic migraine. Secondary study endpoints included reduction of at least 50% 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.
"These positive results are exciting because they add to the growing body of evidence supporting erenumab for the prevention of migraine."
Patients experienced a 6.6-day reduction from baseline in monthly migraine days in each of the erenumab treatment arms as compared to a 4.2-day reduction in the placebo arm, a significant reduction in each erenumab treatment arm.
Secondary endpoint data were not disclosed.
"We were expecting the company to report whether the secondary endpoints were met, especially the 50% reduction rate," said analysts from Leerink Partners. "While the primary endpoint of change in monthly migraine days is the required regulatory endpoint used by Amgen and the other anti-CGRP developers, the responder analysis is very important as it shows the drug's ability to relieve patients from their migraines."
Competitors
Erenumab entered Phase III in the middle of 2015, around the same time as Eli Lilly & Co.'s LY-2951742, another monoclonal antibody CGRP inhibitor being developed for migraine prophylaxis. Later last year, Alder BioPharmaceuticals Inc. took its offering, ALD-403, into Phase III and January this year saw Teva Pharmaceutical Industries Ltd. begin Phase III trials with TEV-48125 (formerly LBR-101), both also monoclonal antibody CGRP inhibitors.
Inferior?
The Leerink analysts also suggest that Amgen's data look slightly inferior to comparative data from two of its competitors.
"ALD403 300 mg achieved a mean change in migraine days of 7.8 vs. 4.9 with placebo," they noted. "Teva's TEV-48125 achieved a reduction of 2.37 days vs. 0.75 days with placebo. From data disclosed to date, we know that AMG-334 achieved a 50% reduction rate of 46.5% (vs. 29.9% with placebo) at 4 weeks vs. ALD-403's rate of 61% (vs. 33% with placebo). Teva's TEV-48125 achieved a 50% reduction rate of 70.4% (vs. 45.2% with placebo). 52-week data from Amgen's open-label extension study showed a 50% reduction rate of 62%, which is on par with ALD-403's rate at 4 weeks."
Teva is hedging its bets on the CGRP front with a separate collaboration with Sosei's Heptares for a small molecule CGRP inhibitor program. Heptares believes small molecules present the opportunity for delivery using routes that are not available to biologics, such as oral or intra-nasal, and for patients with different needs, such as in acute therapy. (Also see "Teva Backs Small Molecule CGRP Approach To Migraine With Heptares Deal" - Scrip, 25 Nov, 2015.)
Discontinuation rates are high for oral preventive drugs for migraine, so there is a significant need for new approaches. That's why biologic medicines, such as monoclonal antibodies, are likely to prove popular with neurology specialists, the companies believe.