New medicine for acute migraine treatment! The oral CGRP receptor antagonist ubrogepant will be approved by FDA this month!

December 7, 2019 / BIOON / -- Allergan recently announced that the positive results of evaluating the application of ubrogepant in the phase III clinical study of acute treatment of adult migraine, acieve I (ubr-md-01), had been published in the New England Journal of Medicine (NEJM) on December 5 The data further confirmed that in terms of acute migraine treatment, the proportion of patients treated with two doses of ubrogepant (50mg and 100mg) who achieved no pain and no migraine related most annoying symptoms at 2 hours after administration was significantly higher than that of placebo group Currently, the new drug application (NDA) of ubrogepant for acute treatment of adult migraine is under review by the US FDA, which will make a review decision in December this year If approved, ubrogepant will become the first oral calcitonin gene-related peptide (CGRP) receptor antagonist for acute migraine (with or without aura) Achieve I is a multicenter, double-blind, parallel group III study that evaluated the efficacy, safety, and tolerability of ubrogepant (50mg and 100mg) compared with placebo in the treatment of acute migraine attack with moderate or severe headache pain intensity In this study, 1672 adult patients (18-75 years old) with migraine history (with or without aura) were randomly assigned (1:1:1) to receive placebo, ubrogepant 50mg and ubrogepant 100mg The common main efficacy parameters of the study were pain relief (no pain) 2 hours after the initial dose and no most annoying migraine related symptoms 2 hours after the initial dose The most annoying migraine related symptoms may include photophobia, voice phobia, or nausea, selected by the subject at the time of migraine onset The secondary efficacy endpoint also assessed the clinical benefits of ubrogrepant in a range of outcome measures, including 2-hour pain relief, 2-24-hour continuous pain relief, and 2-24-hour continuous pain relief (no pain) Adverse events were collected and evaluated 48 hours after the first and optional second administration and 30 days after any one administration The results showed that in terms of two common primary endpoints, the proportion of patients who achieved pain relief (no pain) 2 hours after the initial administration was significantly higher and the data was statistically significant (11.8% in the placebo group, 19.2% in the 50mg group, 21.2% in the 100mg group) than that in the placebo group (50mg and 100mg) The proportion of patients with headache related symptoms was higher and the data was statistically significant (27.8% in placebo group, 38.6% in 50mg group and 37.7% in 100mg group) In addition, in terms of the secondary end point of pain relief 2 hours after administration, the two doses of ubrogepant treatment group showed significant improvement compared with the placebo group (49.1% in the placebo group, 60.7% in the 50mg group and 61.4% in the 100mg group) Pain relief was defined as a reduction in headache severity from moderate to severe to mild or no pain at 2 hours after initial administration This secondary end point was most similar to the primary end point of migraine drugs previously approved by the FDA, such as traptan In addition, the two doses of ubrogepant were statistically superior to placebo (20.8% in placebo group, 36.3% in 50mg group and 38.0% in 100mg group) In this study, both 50mg and 100mg doses of ubrogepant were well tolerated, and the characteristics of adverse events were similar to those of placebo There was no serious adverse reaction, the most common adverse reaction was nausea, which was 1.6% in placebo group, 1.7% in 50mg group and 4.1% in 100mg group The incidence of adverse events in all treatments was similar to placebo (12.8% in placebo group, 9.4% in 50mg group and 16.3% in 100mg group) At present, triptan is the most commonly used drug in the treatment of migraine, accounting for 70% of the prescription However, 67% of migraine patients reported that they would delay or avoid taking prescription drugs when migraine attack, usually because of the adverse events they encountered during the treatment In addition, about 20% of migraine patients have multiple cardiovascular (CV) risk factors, while tritan drugs have vasoconstrictive effect, which may not be suitable for migraine patients with CV risk factors Up to 30% of patients taking traptan may not respond adequately or may have side effects The molecular structure formula of ubrogepant (picture source: Wikipedia) in the United States, the new drug application (NDA) of ubrogepant is based on the successful completion of 4 clinical studies 2 key phase III studies (ACHIEVE I, ACHIEVE) 2) And two additional safety studies (ubr-md-043110-105-002) that demonstrated the efficacy, safety, and tolerance of ubrogepant for acute migraine treatment in a wide range of patient groups, including patients with inadequate response to traptan, patients with contraindications to traptan, and patients with moderate to severe cardiovascular risk characteristics Ubrogepant is a new, efficient, oral calcitonin gene-related peptide (CGRP) receptor antagonist, which has been developed for the treatment of acute migraine CGRP and its receptor are expressed in the nervous system related to the pathophysiology of migraine CGRP receptor antagonism is a new mechanism of acute migraine treatment, which is different from the existing triptans (serotonin 1B / 1D agonists) and opioids At present, CGRP receptor has become a hot target of migraine drug development Up to now, there are three McAbs targeting CGRP receptor for migraine prevention and treatment drugs on the market, respectively: Novartis / ammovig (erenumab aooe), ajovy (fremanezumab vfrm) and emgality (galcanezumab gnlm) In terms of medication, aimovig and emgality are injected subcutaneously once a month, ajovy can be injected subcutaneously once a month or once every three months, which is more convenient in terms of medication and will provide patients with a differentiated treatment option In addition, the company's monoclonal antibody eptinezumab (intravenous infusion once in March) also filed an application for listing in the United States in late February this year Other companies are developing oral CGRP inhibitors, including biomegepant from biohaven, in addition to ubrogepant and atogepant from Elgin In October, leyvow (lasmiditan) was approved by the US FDA for acute treatment of migraine in adults with or without aural symptoms The approval is significant because reyvow represents the first new class of acute migraine drugs approved by FDA in more than 20 years The active ingredient of the drug is lamiditan, which is an oral, central nervous system permeable, selective, 5-hydroxytryptamine 1F (5-HT1F) agonist It is different from the approved migraine drugs in structure and mechanism, and has no vasoconstrictive activity It is worth mentioning that lasmiditan is the first and only drug molecule approved for acute treatment of migraine in adults This approval represents the first major innovation in the treatment of acute migraine in more than 20 years Original source: Allergan announcements positive phase 3 achievement I trial results for ubrogepant published in the New England Journal of Medicine