Datamonitor recently attended the 63rd American Academy of Neurology Annual Meeting in Honolulu, Hawaii, held over April 9-16, 2011. Below are the highlights of the conference's coverage of new migraine drugs.
Few major developments were announced in the migraine field at the 63rd American Academy of Neurology Annual Meeting (AAN 2011), with no new clinical data presented for the more promising late-stage pipeline candidates. Nevertheless, Allergan boasted a strong presence to promote the use of Botox (onabotulinumtoxinA) injections for patients with chronic migraine, an underserved patient population. Elsewhere, MAP Pharmaceuticals and Zogenix sought to educate delegates about the benefits of their rapid-acting technologies for acute migraine. Merck & Co. provided some encouraging cardiovascular safety data for its first-in-class calcitonin gene-related peptide (CGRP) receptor antagonist, telcagepant.
MAP Pharmaceuticals: Levadex shown to be effective when given during migraine attacks
Levadex, under development by MAP Pharmaceuticals, is an inhaled formulation of the ergotamine derivative dihydroergotamine (DHE), using the company's proprietary Tempo drug delivery technology, for the potential acute treatment of migraine. DHE in non-inhaled forms has been used for over six decades in the treatment of migraines. In previous clinical studies, Levadex has been shown to have a similar Tmax to intravenous DHE but a lower Cmax, which results in less nausea, a common side effect with intravenous DHE.
Having completed Phase III efficacy development, MAP is conducting four additional clinical trials - an open-label safety trial, a pharmacokinetics study, a pharmacodynamics study, and a QT interval trial - to support its New Drug Application (NDA) submission, which it plans to file in the first half of 2011.
MAP presented some of its data from these trials at AAN 2011. The poster presentations were mainly focused on describing a favorable safety and pharmacokinetic profile for Levadex. Dr Shashidhar Kori described the benefits of using Levadex during a migraine attack, when the efficacy of triptans is typically reduced. The rationale for the study is that many patients often wait before taking their medication, despite evidence to suggest early intervention is best and that late intervention with triptans is less effective. This post-hoc analysis of a Phase III trial (n=771) demonstrated the efficacy of Levadex in treating moderate or severe acute migraine attacks, even when administered more than eight hours after the start of a migraine. Showing efficacy in this real world situation will be an advantage for Levadex over other acute therapies.
Zogenix and Astellas: high patient acceptance of Sumavel DosePro, though price remains a limiting factor
In January 2010, Zogenix and its co-promotion partner Astellas announced the US commercial launch of the Sumavel DosePro (sumatriptan injection) needle-free delivery system for the acute treatment of migraine, with or without aura, and the acute treatment of cluster headaches. Sumavel DosePro is a rapid-acting sumatriptan formulation in a simple to use, needle-free delivery system for self-administration. However, a high reimbursement tiering means that there is a large co-pay associated with the product, and the high price will hinder uptake, particularly as generic sumatriptan injections are already available. Nevertheless, the marketing partnership with Astellas will enhance penetration of the primary care market.
The companies gave two poster presentations for Sumavel DosePro at AAN 2011. The first poster presented results from an open-label study showing that Sumavel DosePro improved treatment satisfaction and confidence among current triptan users trying Sumavel DosePro for up to four migraine attacks. In the second poster, an open-label study (n=212) showed that Sumavel DosePro was associated with rapid, sustained headache relief, and was well tolerated in the treatment of multiple migraine attacks among current triptan users. Both posters support the clinical and patient acceptance profile of Sumavel DosePro, but are unlikely to be sufficient to convince increasingly frugal healthcare payers to extend reimbursement coverage.
Allergan: strong focus on the potentially lucrative chronic migraine use of Botox
In October 2010, Allergan's Botox became the first drug to be approved by the US FDA for the prophylactic treatment of headaches in adults with chronic migraine. Chronic migraine is characterized by patients who have a history of migraine and suffer from headaches on 15 or more days per month, with headaches lasting four hours a day or longer. Botox is injected at labeled doses and in the recommended locations in the head and neck, and is expected to be effective for up to three months.
Allergan chose AAN 2011 to present positive findings from the Phase III PREEMPT clinical trial program, the results of which were originally announced in early 2010. The company also boasted a large Botox stand in the exhibition hall to promote the migraine and non-migraine uses of its product to delegates. Datamonitor believes that Allergan was successful in promoting the benefits of Botox for chronic migraine, which is important given that the US will provide the majority of migraine revenues for the brand.
Professor David Dodick gave an oral presentation providing analysis that supported the efficacy and safety of Botox use in chronic migraine from the PREEMPT Phase III clinical trial program (n=1,384). The PREEMPT clinical program demonstrated that Botox yielded significant improvements over placebo across multiple headache symptom measures, including reduction in headache days. A poster presentation provided further analysis from the PREEMPT program, showing that Botox treatment is associated with improved emotional and physical functioning, and overall health-related quality of life.
Merck & Co.: telcagepant's cardiac profile looks promising
Merck & Co.'s telcagepant (MK-0974) is the leading investigational oral CGRP receptor antagonist in Phase III development for the potential acute treatment of migraine. Datamonitor believes that telcagepant is one of the most promising drugs in late-stage development for migraine based on its novel mechanism of action, favorable efficacy shown in clinical trials, and Merck's experience in the migraine arena. However, safety issues arising from Phase II studies relating to elevated liver enzymes are a concern.
While Merck & Co. did not announce any new efficacy data for telcagepant at AAN 2011, it did present two posters describing the cardiovascular and abuse profile of its drug. In one poster, high dose telcagepant (600mg/560mg daily) was shown to have no effect on 24-hour ambulatory blood pressure or heart rate in healthy volunteers, based on two small double-blind studies (n=34 and n=38). These data will help differentiate telcagepant from triptans, which can produce adverse cardiac events and are contra-indicated in patients with underlying cardiovascular disease.
If larger studies confirm a benign cardiac profile, then Merck will possess a major competitive advantage. In a second poster, telcagepant was shown to have no potential for recreational abuse. The small randomized double-blind crossover study of 32 healthy recreational polydrug users compared telcagepant to alprazolam, a benzodiazepine, which was shown to produce greater abuse potential. Benzodiazepines are used to treat migraine prevention and are associated with a high risk of abuse. Triptans, however, which form telcagepant's main competition in the market, are not associated with a high risk of abuse potential.