- Allergan's experimental headache drug atogepant proved effective at reducing migraines when given preventively in Phase 2b/3 study, clearing a path for the pharma to advance the CGRP inhibitor further into late-stage testing.
- Results announced Monday showed all active doses of atogepant beat out placebo in reducing the average number of monthly migraine days compared to baseline. Notably, Allergan reported no sign of liver toxicity — a key concern for small-molecule CGRP blockers like atogepant.
- Known best for its multi-purpose drug Botox, Allergan is counting on atogepant and another related treatment called ubrogepant to help it stay relevant in the newly competitive migraine field. Just last month, Amgen and Novartis won U.S. approval of Aimovig, a monoclonal antibody that also targets the CGRP receptor.
Allergan has been a player in the migraine market for years, selling Botox as a preventive treatment in the U.S. since its approval for the indication in 2010.
That position is threatened by the arrival of a wave of monoclonal antibodies targeting CGRP, which is thought to play a role in the development of migraine. Amgen and Novartis' Aimovig (erenumab-aooe) is the first of these large molecule drugs to win approval, but similar compounds from Eli Lilly, Teva Pharmaceutical Industries and Alder BioPharmaceuticals are nearing markets as well. Lilly's drug, called galcanezumab, is expected to receive a Food and Drug Administration OK later this year.
Allergan's efforts approach the same pathway, but with an orally administered small molecule.
Development of ubrogepant, designed for acute treatment, and atogepant, for preventive use, has so far avoided the liver toxicity issues that forced the shuttering of clinical testing of earlier small molecule CGRP inhibitors developed by Merck & Co. and Bristol-Myers Squibb.
Allergan believes ubrogepant, which passed a second Phase 3 test in April, could complement both Botox and, potentially, new CGRP inhibitors like Aimovig. As an oral acute treatment, patients administer ubrogepant when their migraines remain uncontrolled — potentially acting as a back-stop to preventive treatment.
Atogepant, then, could give Allergan another prophylatic medicine in its arsenal and allow it to better match up to newcomers.
"Should the data be replicated in a second pivotal trial, atogepant would nicely complement the Botox migraine [and] eventual acute use ubrogepant commercial efforts," wrote Cowen analyst Ken Cacciatore in a June 11 note to investors.
The 834-patient Phase 2b/3 study reported by Allergan Monday found all five doses of atogepant tested significantly reduced mean monthly migraine days over 12 weeks compared to placebo.
Nausea, fatigue, constipation, nasopharyngitis and urinary tract infection all occurred in at least 5% of patients in at least one atogepant arm and with greater frequency than in placebo, Allergan said.
Not all were convinced the data showed atogepant could challenge the anti-CGRP antibodies, however.
"We await further data disclosure and larger patient numbers to be convinced about comparing the efficacy of atogepant to the more advanced injectable CGRP medicines in development," wrote Leerink analyst Geoffrey Porges in a June 12 note.
In particular, Porges noted the reduction in mean monthly migraine days did not appear higher in the treatment groups given larger daily doses of atogepant.
The pharma plans to discuss the results with regulators before continuing with its Phase 3 program for the drug. Cowen's Cacciatore thinks atogepant could be submitted to regulators by 2021 if all goes well.
By then, however, multiple large molecule anti-CGRP treatments could be on the market, potentially altering the preventive market for migraine in dramatic fashion.
Amgen and Novartis, hoping to win market share early, priced Aimovig at $6,900 a year — in line with a cost-effectiveness analysis run by the Institute for Clinical and Economic Review and lower than expected. The relatively moderate price could win over payers and help spur uptake.
Competitive pricing could eventually work in Allergan's favor, as oral, small molecule drugs are usually less costly to produce. In the near-term, however, Amgen, Novartis and potentially others will take their shot at minting a blockbuster migraine drug.