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Rapastinel Flop Leaves Allergan in a Hole

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Rapastinel Flop Leaves Allergan in a Hole March 06, 2019 Rapastinel flop leaves Allergan in a hole Madeleine Armstrong The failure of one of Allergan’s key pipeline projects puts the group’s chief executive under even more pressure. In the battle of the ketamine-like antidepressants Allergan had pitched rapastinel as an agent with a more benign safety profile than Johnson & Johnson’s just-approved Spravato. However, unlike Spravato, there is no sign that Allergan’s candidate actually works. The failure of three phase III trials of rapastinel yesterday might not be a disaster in itself, but it highlights the thinness of Allergan’s late-stage pipeline. The group’s chief executive, Brent Saunders, has faced criticism in recent weeks, and he could now come under more pressure to strike a big deal – or leave the company. Allergan's late-stage pipeline highlights 2024e Project Indication Note sales ($m) Acute Ubrogepant 425 FDA filing due Q1 2019 migraine Rapastinel Depression 359 Failed 3 ph III trials Migraine Ph III trial in chronic migraine to start Atogepant 297 prevention H1 2019 Bimatoprost Glaucoma 206 FDA filing due H2 2019 SR Ph III Maple trial of new formulation Abicipar Wet AMD 178 due H1 2019 Relamorelin Gastroparesis 86 Ph III Aurora trial due to complete Cenicriviroc Nash 28 2020 Source: EvaluatePharma. Activist shareholders have long been agitating for change at Allergan, and the latest failure will only provide more ammunition to those who want to split the roles of chairman and chief exec amid dissatisfaction with the group's acquisition strategy, and with its stock hovering around a five-year low. Both positions are held by Mr Saunders, who has resisted calls for such a separation, at least until he is ready to throw in the towel. Rapastinel, which Allergan gained through its $560m acquisition of Naurex in 2015, is hardly a glowing example of Mr Saunder's deal-making skills. It does not look like anything can be salvaged from the three phase III studies – RAP-MD-01, RAP-MD-02 and RAP-MD-03 – that had evaluated rapastinel on top of standard antidepressants in patients with a partial response to the existing drugs. Allergan did not give many details, but said all three trials failed to show a benefit with the NMDA modulator versus placebo on the primary endpoint, change in Montgomery-Asberg depression rating scale at three weeks, as well as flunking key secondary endpoints. And an ongoing relapse prevention study, RAP-MD-04, also looks unlikely to succeed after an interim look, the company added. Several trials of rapastinel are continuing, including those evaluating the project for suicidality prevention and as a monotherapy in depression, but there cannot now be much hope for them. Quantity, not quality Allergan’s attention will now turn to the rest of its pipeline, which looks like an exercise of quantity over quality. The next big event will come courtesy of its marketed antipsychotic Vraylar, which is due a decision from the FDA in bipolar depression in May. Meanwhile, Allergan’s brightest pipeline hopes are its oral CGRP inhibitors, ubrogepant and atogepant, which are both being developed for migraine. Ubrogepant should soon be filed with the FDA for the acute treatment of migraine, where it could go up against Biohaven’s rival oral CGRP rimegepant. And atogepant, designed to prevent migraines, is in phase III. Oral pills should be more patient-friendly than the injectable CGRPs currently on the market, but the migraine space is becoming crowded. Some of Allergan’s other pipeline prospects are less promising. The wet AMD candidate abicipar did technically succeed in its pivotal trials, but the win was marred by a high incidence of intraocular inflammation (Allergan’s eye contender cannot knock Eylea off its perch, 20 July 2018). The future of the project depends on the upcoming Maple trial, which is testing a new formulation that Allergan hopes will reduce this side effect. And expectations are low for the Nash project cenicriviroc, which the company picked up with its $534m acquisition of Tobira. Allergan recently pushed back the readout of the Aurora trial to 2020, and study delays are rarely a good sign. Nash has proven a tough nut to crack, with Gilead’s selonsertib and Intercept’s Ocaliva yielding disappointing results in the past few weeks. Allergan’s stock opened up 3% today, suggesting that investors had not been holding out much hope for rapastinel and that they are relieved it will not be spending much more money on it. But any more stumbles could strengthen calls for the company to do something drastic – and could make it hard for Mr Saunders to hang on to his job. NMDA projects in depression 2024e sales Project Company Pharma class Status ($m) Johnson & Spravato NMDA antagonist 1,556 Approved Johnson Rapastinel Allergan NMDA receptor partial agonist 359 Phase III Norepinephrine, dopamine reuptake inhibitor Axsome AXS-05 (bupropion) plus NMDA antagonist 211 Phase III Therapeutics (dextromethorphan) Vistagen AV-101 AMPA agonist and NMDA antagonist 68 Phase II Therapeutics Source: EvaluatePharma. More from Evaluate Vantage Evaluate HQ 44-(0)20-7377-0800 Evaluate Americas +1-617-573-9450 Evaluate APAC +81-(0)80-1164-4754 © Copyright 2021 Evaluate Ltd..
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