- With more positive Phase 3 data in hand, Allergan intends to file its migraine treatment ubrogepant for U.S. approval early next year.
- Clinical results announced late last week showed that, compared to placebo, a significantly greater percentage of patients treated with ubrogepant met the pivotal ACHIEVE II study's co-primary endpoint of pain freedom two hours after initial dose. The study tested 25 mg and 50 mg doses of Allergan's drug, both of which met that endpoint.
- The other co-primary endpoint was absence of the most bothersome migraine symptom two hours after initial dose. On that measure, only the 50 mg dose significantly outperformed placebo. As for safety, Allergan said there were four cases of aminotransferase elevations between three and five times the upper limit of normal. A blinded panel of liver experts determined these events weren't likely related to ubrogepant treatment.
Ubrogepant is heading to the Food and Drug Administration backed by two positive late-stage trials and a long-term safety study expected to wrap up in October. While that puts it in a good position for approval, Allergan investors have sought assurance it can compete in what's becoming a crowded area of drug development.
A new wave of migraine treatments could hit the market as early as May. Called calcitonin gene-related peptide (CGRP) inhibitors, they include both oral versions that are meant to treat chronic migraines after they happen and injectable versions that are seeking to prevent the burdensome headaches in the first place.
Allergan's ubrogepant and Biohaven Pharma's rimegepant are both of the oral variety. But the injectables are advancing rapidly, including Amgen and Novartis' Aimovig (erenumab), which is likely to gain approval in the coming months.
The specialty pharma held a conference call Friday, during which David Dodick, a professor of neurology at the Mayo Clinic in Phoenix, fielded questions about where ubrogepant would fit into clinical practice. Dodick noted that, from his experience, 30% of patients are non-responsive to triptans (a common therapy for headaches) and 10% to 15% are intolerant.
He added that the biggest prescribing factor with those patients is headache relief, making ubrogepant an enticing option given its effect on pain freedom after two hours.
The drug could also pair nicely with other available migraine treatments.
"Could I conceive of a medication like ubrogepant being effective in a patient who's on a monoclonal antibody that targets the ligand or the receptor? Yeah, I could, because these antibodies have different association and dissociation constants, so they jump on and jump off the peptide, or jump on and jump off the receptor," Dodick said.
"So with the burst of CGRP at the synapse, you can imagine that some of the receptors will be unoccupied and a receptor antagonist like ubrogepant might provide efficacy."
Yet concerns still hover over the drug's safety, largely due to the liver signals seen in ACHIEVE II. Several years ago, liver toxicity issues caused Merck & Co. to shutter development of its candidate telcagepant, casting doubts over small molecule CGRP drugs.
On the Friday call, analysts questioned how the liver safety signals seen in ACHIEVE II would impair ubrogepant's ability to compete with other CGRP antogonists — particularly Biohaven's rimegepant, which has a similar mechanism of action but looks to have a cleaner toxicity profile.
"We, at the moment, see no confirms regarding hepatotoxicity with ubrogepant. So it looks like we have a very effective drug and also a very safe drug," said David Nicholson, Allergan's head of R&D.
Allergan plans to submit three doses — a 25 mg, a 50 mg and a 100 mg — of ubrogepant for approval in the first half of 2019. The company anticipates presenting more data from ACHIEVE II later this year at upcoming scientific meetings.