dm+d

Unassigned

New Medicines

UbrelvyMigraine - acute treatment

Information

Ubrelvy
New molecular entity
Allergan
Allergan

Development and Regulatory status

None
None
Launched
Feb 20In its latest annual report, Allergan does not describe any plans to file for approval of ubrogepant in the EU [16].
Feb 20Annual list price in the US of Ubrelvy is $4,896 [14]
Dec 19Approved in the US for treatment of acute treatment of migraine in adults, with or without aura. The decision makes Ubrelvy the first oral CGRP receptor antagonist approved in the US to treat acute migraines once they start [13].
Aug 19Allergan plans to launch ubrogepant in the US in H1 2020; plans for EU development not stated [12].
Mar 19Filed in US [10].
Sep 18Topline PIII results expected, with launch in 2020 [9].
May 18Analysts predict US launch in 2020, and launch in other countries starting in 2021 [8].
Feb 18Allergan annouced that it anticipates filing of a New Drug Application (NDA) to the FDA in 2019.[6]
Mar 17Company expects launch to be in 2020 [3].
Aug 16Pivotal PIII trials started; estimated completion Dec 17 [4].
Jul 15Allergan has purchased exclusive rights to Mercks experimental oral calcitonin gene-related peptide (CGRP) receptor antagonists, which include MK-1602. Under the deal, Allergan takes full responsibility for development of the CGRP programs, as well as manufacturing and commercialisation upon approval and launch of the products. Merck will receive development and commercial milestone payments and tiered royalties based on commercialisation of the programs [1].

Category

Calcitonin gene-related peptide (CGRP) receptor antagonist, orally-active small molecule
It is estimated that there are 190,000 migraine attacks experienced every day in England and 6 million people suffer from migraine in the UK. Prevalence has been reported to be 5–25% in women and 2–10% in men. Prevalence of chronic migraine in the UK is not known, although some clinicians consider the rate could be 1 in 1000 people [2].
Migraine - acute treatment
Oral

Trial or other data

Dec 19Results of ACHIEVE 1 study (NCT02828020) published in NEJM [13].
Apr 18Positive results from pivotal, PIII, multicentre, randomised, double-blind, placebo-controlled, parallel-group study (ACHIEVE II, UBR-MD-02) for ubrogepant for the acute treatment of migraine. The study included 1,686 pts in the US randomised (1:1:1) to placebo, ubrogepant 25 mg and 50 mg respectively, to treat a single migraine attack of moderate-to-severe headache intensity. Co-primary efficacy parameters were pain freedom (PF) at 2 hours after the initial dose and absence of the most bothersome migraine-associated symptom (photophobia, phonophobia or nausea) at 2 hours after the initial dose. In the mITT population (n=1355), the percentage of pts achieving pain freedom at 2 hours after the initial dose was; 25 mg vs placebo, p=0.0285, 50 mg vs placebo, p=0.0129. The percentage of pts achieving absence of the most bothersome migraine-associated symptoms at 2 hours after the initial dose was statistically significant for the 50 mg dose (50 mg vs placebo, p=0.0129) but not for the 25mg dose. Ubrogepant was well tolerated and demonstrated a safety profile similar to placebo. There was no signal of hepatotoxicity for ubrogepant within 30 days of dosing. The most common adverse events were nausea and dizziness (frequency <2.5%).[7]
Feb 18Positive Top Line Phase 3 Results for Ubrogepant announced from the ACHIEVE I study (NCT02828020, n=1327). Pts were randomised (1:1:1) to placebo, ubrogepant 50 mg and 100 mg - they were treated for a single migraine attack of moderate to severe intensity. Both doses showed a statistically significant greater percentage of ubrogepant pts achieving pain freedom at 2 hours after the initial dose vs. placebo (50 mg vs placebo, p=0.0023, 100 mg vs placebo, p=0.0003) and a statistically significant greater percentage of ubrogepant pts achieving absence of the most bothersome migraine-associated symptoms (including photophobia, phonophobia or nausea) at 2 hours after the initial dose vs. placebo (50 mg vs placebo, p=0.0023, 100 mg vs placebo, p=0.0023). Ubrogepant was well tolerated with an adverse event profile similar to placebo. The most common adverse events were nausea, somnolence, and dry mouth, none of which were reported with a frequency of ≥5%. Results of the 2nd PIII trial, ACHIEVE II (UBR-MD-02), are expected in H1 2018.[6]
Sep 17PIII trial (NCT02867709) is currently recruiting patients. No change to timescales. PIII trials (NCT02828020) has completed recruitment and expects to complete collection of primary outcome data in Jan 18 [5].
Aug 16Second of two PIII trials started (NCT02867709) - this has a similar design and estimated recruitment to NCT02828020, but compares ubrogepant doses of 25 mg and 50 mg and placebo; estimated completion is Dec 2017 [4].
Jul 16First of two PIII trials started (NCT02828020), a randomised placebo-controlled trial comparing the efficacy and safety of two doses of ubrogepant (50 mg, 100 mg) and placebo in acute migraine. Primary outcomes are freedom from pain and freedom from the most bothersome symptom at two hours; estimated recruitment is 1650 and estimated completion November 2017 [4].

Evidence based evaluations