AAN 2013 preview: no game changers but pipeline developments aplenty.
By Daniel Chancellor, Lead Analyst
27 February 2013
I am a Lead Analyst covering the CNS and rare disease markets at Datamonitor Healthcare. I joined in early 2010, having ...
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Over March 16–23, San Diego will play host to the 65 American Academy of Neurology (AAN) Annual Meeting, the largest annual conference dedicated to the field of neurology. In keeping with tradition, the AAN has published scientific abstract details online in advance of the meeting. This article provides a preview of the conference and highlights presentations to look out for.
Previous years will be a tough act to follow for multiple sclerosis research
Recent AAN conferences have provided a feast of information on emerging multiple sclerosis drugs and 2013 appears to be no exception. However, the only new Phase III study of a new disease-modifying drug set to be showcased at this year’s meeting is Biogen Idec’s ADVANCE trial for PEG-Avonex (peginterferon beta-1a), its successor to the market-leading interferon beta product Avonex. Biogen has already announced top-line data, in which both fortnightly and monthly PEG-Avonex dosing met all primary and secondary endpoints compared to placebo, including relapse rate and disability progression. Look out for a presentation revealing important clinical differences between the two dosing regimens on Wednesday 20, although Biogen has opted against comparing PEG-Avonex to Avonex. Also that day, Acorda will be at the AAN with detailed results of its post-marketing study to investigate the efficacy and safety of a lower dose of Ampyra (fampridine). Ampyra is currently approved to improve walking in patients with multiple sclerosis in both the US and EU, although it is not a disease-modifying drug.
The US Food and Drug Administration (FDA) is due to issue its decision on the approval of Biogen Idec’s Tecfidera (BG-12/dimethyl fumarate) for relapsing-remitting multiple sclerosis on March 28, one week after the conclusion of AAN 2013. It is no surprise then that Tecfidera features prominently at the meeting, with numerous posters analyzing the minutiae of its impressive pooled clinical data. A systematic literature review, to be presented on Thursday 21, suggests that Tecfidera has comparable efficacy on relapse reduction to Gilenya (fingolimod; Novartis) and is only inferior to Tysabri (natalizumab; Biogen Idec). Available data support its superiority over the current first-line injectable treatments.
With no other pivotal trials for the current crop of new launches and late-stage pipeline multiple sclerosis drugs completing in the previous 6 months, the majority of data presented concern open-label safety extensions and detailed analyses on secondary endpoints. Novartis will be presenting 4-year safety data for Gilenya, as well as multiple indirect comparisons between Gilenya and Tysabri, suggesting that Novartis is targeting Tysabri’s market share. Sanofi also has some limited exposure at AAN with analyses of data from its Aubagio (teriflunomide) trials. In a similar vein, numerous posters will explore the long-term safety of Lemtrada (alemtuzumab; Sanofi/Bayer), daclizumab (Biogen Idec/AbbVie), and ocrelizumab (Roche), all of which represent potential market entrants offering high efficacy alongside possible safety concerns. Additionally, results of open-label extension studies for ponesimod (Actelion) and siponimod (Novartis), both vying to become second-in-class sphingosine-1-phosphate (S1P) receptor agonists behind Gilenya, will be presented.
2012 trials and tribulations of bapi/sola quickly consigned to history in fast-moving Alzheimer’s disease field
It had been hoped that 2012 would represent a breakthrough year for Alzheimer’s disease research, as the mammoth clinical programs for bapineuzumab (Johnson & Johnson/Pfizer) and solanezumab (Eli Lilly) came to fruition. However, the failed bapineuzumab trials do not feature among the list of AAN presentations, while Eli Lilly has just a small presence devoted to the intriguing glimpse of efficacy revealed during its EXPEDITION solanezumab studies. Although efficacy results from EXPEDITION were debuted toward the end of 2012, biomarker endpoints will be explored in a poster presentation on Monday 18. These will help inform the direction of clinical studies of future beta amyloid-targeting drugs, not to mention their relevance for the redesign of Lilly’s own Phase III program for solanezumab, currently scheduled to restart by no later than Q3 2013.
One presentation to look out for, also on Monday 18, involves Octapharma’s study of its intravenous immunoglobulin (IVIG) preparation Newgam in patients with mild cognitive impairment (MCI) due to Alzheimer’s disease. Treatment with IVIG was associated with decreased brain atrophy and improvement in cognition over a 1-year time period, although the small sample size (n=51) and non-significant results should be noted. Nevertheless, this provides an exciting proof-of-concept for IVIG in the earlier stages of Alzheimer’s disease; Baxter has provided similar data for its IVIG product, Gammagard, in mild to moderate Alzheimer’s disease and may soon be announcing initial results from a larger, more robust Phase III program. Also, the most advanced alpha-2c adrenoreceptor antagonist in development for Alzheimer’s disease, Orion Pharma’s ORM-12741, has completed a proof-of-concept Phase II trial with the results to be announced in an Emerging Science session on Wednesday 20.
The Parkinson’s disease drug pipeline may be starting to show promise
In Parkinson’s disease, look out for new data on Azilect (rasagiline; Teva/Lundbeck), tozadenant (BioTie Therapies/UCB), and pimavanserin (Acadia). Teva and Lundbeck will be presenting results from the ANDANTE study, which explored the addition of Azilect to dopamine agonists in early Parkinson’s disease. BioTie has recently completed a 420-patient Phase IIb/III study of tozadenant in levodopa-treated Parkinson’s disease patients, in which drug treatment yielded highly significant effects versus placebo across multiple endpoints, including decreased “off” time, increased “on” time, and improvements in Unified Parkinson’s Disease Rating Scale (UDPRS), clinician-, and patient-assessed global impression scores. Acadia’s pivotal Phase III pimavanserin study, first announced in November 2012, revealed significant treatment effects for Parkinson’s disease psychosis. Other noteworthy presentations include reviews of Newron’s pivotal MOTION and SETTLE trials of safinamide, posters of the long-term safety of Impax’s Rytary/IPX066 (carbidopa-levodopa), and details from Addex’s Phase II trial of its first-in-class mGluR5 negative allosteric modulator dipraglurant.
Late-breaking presentations could provide the headline news from AAN 2013
As always at the AAN, late-breaking presentations provide the ideal platform to announce new clinical data and these are not listed among the abstracts before the conference. Merck’s suvorexant for insomnia, currently under regulatory review, is notably absent from the pre-published list of abstracts, while further clinical data for Gammagard, subcutaneous bapineuzumab (Johnson & Johnson/Pfizer), and SAR110894 (Sanofi) for Alzheimer’s disease, CERE-120 (Ceregene) for Parkinson’s disease, and IPX159 (Impax) in restless legs syndrome are expected in the near term.