Starting this Sunday, July 24th, the Alzheimer’s disease (AD) community will turn its eyes to Toronto as the 2016 Alzheimer’s Association International Conference (AAIC)—one of the biggest worldwide meetings for AD clinicians, investigators, scientists, and drug developers—gets underway. DRG will be on the ground at the Metro Toronto Convention Centre, and here are some things we will be keeping a close eye on.

Will Tau Outshine Amyloid This Summer?

Amyloid-targeted therapies have long been the focus of AD drug development, but it’s possible that a tau therapy could beat the amyloid contenders to the finish line. On Wednesday, initial results from the Phase III trials of TauRx’s LMTX (a second generation version of methylthionium chloride), a tau aggregation inhibitor for the treatment of mild/mild to moderate AD, will be presented (Session O4-08-02). Phase II data from an earlier formulation showed some promise, with one of three doses demonstrating efficacy on the ADAS-cog at 24 weeks in moderate AD and at 50 weeks in mild to moderate AD1, but historically Phase II results have not been a reliable barometer for late-phase success in AD. While LMTX has flown under the radar for some time, you can expect that if these data prove positive, they will steal the show at this year’s meeting. LMTX could be the first putative disease-modifying therapy (DMT) to reach the FDA, a huge milestone in AD… or it could be another in a long line of failed DMTs.

Also presenting in this session is vTv Therapeutics, with Phase II data from its RAGE inhibitor azeliragon (Session 04-08-05) and Eli Lilly, with Phase I data from its Aß-monoclonal antibody LY3002813 (Session 04-08-06).

All About That BACE

A number of developers will be presenting data on investigational BACE inhibitors this week, including a Sunday session on Aß clinical trials (Session 01-10) featuring Janssen’s oral BACE-1 inhibitor JNJ-54861911 and Novartis’s oral BACE-1 inhibitor CNP520. Other BACE inhibitors being highlighted include AstraZeneca and Eli Lilly’s AZD3293 (P2-002), Eli Lilly’s LY3202626 (P1-044), and Merck’s verubecestat (P4-380). While many of these presentations will feature either early phase study results or baseline characteristics of Phase III studies, these drugs are ones to watch. BACE inhibitors could become preferred DMTs given the oral delivery of most drug candidates—it’s too early to know if efficacy could differentiate them or any other DMTs—but safety will be key and remains a lingering question mark in light of Eli Lilly’s discontinuation of LY02886721 because of an association with liver toxicity in 2013.

An Eye Toward the Future: Prevention Trials

A Wednesday morning symposium on AD prevention trials (F4-03) promises to bring together “key leaders” of the DIAN (NCT01760005), A4 (NCT02008357), and API (NCT01998841) studies to discuss “early successes and challenges from each trial and highlight how they are informing the development of the next generation of trials in AD prevention.” We all know early intervention will be critical to the success of DMTs, but the ongoing prevention trials assessing DMT effects in preclinical AD (i.e., at-risk, asymptomatic patients) represent the ultimate test in achieving this goal.  These studies, which vary widely in methodology and design, will be an important step in understanding the preclinical characteristics of AD and determining how to identify AD patients prior to the onset of cognitive symptoms—and, of course, establishing if anti-amyloid drugs from Eli Lilly and Roche/Genentech are efficacious in these populations. Many of these trials are not expected to read out until 2019-2020, but some early insight into their progress should be enlightening; positive results would be paradigm-shifting.

What Else?

Improved symptomatic treatments in AD are still an area of significant opportunity. Two late-stage procognitive, symptomatic, 5HT-6 receptor antagonists, Axovant’s intepirdine (RVT-101) and Lundbeck/Otsuka’s idalopirdine, will be represented in poster presentations at AAIC 2016 (P1-056, P3-014, P4-001). While the earliest results from ongoing Phase III trials of idalopirdine aren’t expected until late 2016, the presentation may give us a status update. Similarly, increasing focus has been placed on behavioral symptoms associated with AD, notably agitation, and a number of presentations will focus on management of these symptoms (e.g., O2-1401, P3-021, P1-047) as well as some emerging therapies targeted to these symptoms (e.g., Nabilone, PF-05212377). To date, we count at least six companies developing new drugs specifically for AD agitation, for which no drugs are approved.

In addition to these great topics, we hope AAIC 2016 also provides a few surprises. Either way, DRG will be there to see it and incorporate theses insights into our upcoming offerings in AD, including Disease Landscape & Forecast, Special Topics (focusing on emerging therapies), and Access and Reimbursement (US).

 

  1. Wischik CM. Tau Aggregation Inhibitor Therapy: An Exploratory Phase 2 Study in Mild or Moderate Alzheimer’s Disease. J Alzheimers Dis. 2015; 44:705-720.

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