Who To Watch In The Alzheimer's Treatment And Research Space
By Anna Rose Welch, Editorial & Community Director, Advancing RNA
In an interview with the Triangle Business Journal, Eli Lilly CEO John Lechleiter said 2/3 of drugs fail to show efficacy in Phase 2 trials because there isn’t enough understanding of the targeted disease. He tells the Journal, “While drug hunting remains a vital activity… I think we need to advance, like our ancestors did, from hunting to farming, cultivating the knowledge of disease.”
Pharma is faced with finding answers to some tricky illnesses. In particular, Alzheimer’s disease is burdened with clinical difficulties and, therefore, stunted pipelines. In 2013, Obama launched the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative. This project is dedicated to, among other things, garnering more insights into the brain’s neurons to determine treatment methods for Alzheimer’s. This is a welcome $300 million effort, but in looking at NIH funding in particular, the $600 million allocated for Alzheimer’s pales in comparison to the $5 billion for cancer. Considering the disease population is expected to more than triple to 16 million Americans (and cost $1.2 trillion to treat) by 2050, I’m hoping to see these funding efforts increase in the near future.
I haven’t heard of any big breakthroughs in terms of a prospective treatment for Alzheimer’s as of late. However, according to PhRMA, there are 81 Alzheimer’s drugs in clinical trials or awaiting review by the FDA, along with several newly launched initiatives/new startups aiming to get a better sense of the biology of the disease — in keeping with Lechleiter’s advice.
Here are just a few of the ongoing efforts in the Alzheimer’s space I’ve come across recently (starting with the most recent):
- The NIH just launched a new Alzheimer’s Big Data portal as part of the Accelerating Medicines Partnership (AMP). This new portal will facilitate the sharing and analyses of biomedical datasets in order to develop predictive models of Alzheimer’s and identify targets for potential treatments. Reflecting the industry’s current focus on open innovation, the goal of the project is to inspire collaboration and, in turn, accelerate the discovery of and reduce costs of developing new treatments.
- This month, Forbes published an article interviewing Tony Coles, formerly of Onyx Pharmaceuticals, who recently launched the Cambridge, MA-based startup, Yumanity. This company hopes to determine how misfolded proteins in the brain cause Alzheimer’s, Lou Gehrig’s disease, and Parkinson’s. For more information about Yumanity’s discovery platforms, check out this press release about the company’s launch.
- AgeneBio published results from a Phase 2 trial investigating its AGB101 in the pre-dimension stage of Alzheimer’s. In the trial, the drug reduced excess hippocampal activity and improved memory in patients — a move which could delay onset of the disease.
- AstraZeneca and Eli Lilly announced in December 2014 they were launching the AMARANTH Phase 2/3 study, investigating the safety of their oral beta-secretase cleaving enzyme (BACE) inhibitor compared to placebo. The drug, AZD323 or LY3314814 demonstrated efficacy in lowering amyloid-beta levels in the cerebro-spinal fluid of Alzheimer’s patients and healthy volunteers.
- Also in December 2014, Biogen Idec announced that its plaque-buster candidate for Alzheimer’s, BIIB037, reduced amyloid levels in the brain and improved cognition in patients versus placebo in a 54-week study (both secondary endpoints). When evaluating the drug for safety (primary endpoint), researchers did find that BIIB037 caused mild to moderate amyloid-related imaging abnormalities in patients receiving the drug. However, Biogen’s Head of R&D is optimistic and expects to carry the drug further into development, as well as launch some other studies that will evaluate the drug’s performance in different doses.
- Back in October, researchers created Alzheimer’s-in-a-dish, proving the “Amyloid Hypothesis” that a build-up of beta amyloid leads to the development of tau tangles, in turn causing the formation of the disease. This discovery will also provide researchers with a much faster and cheaper way to test plausible drugs than by using mouse models which are different from the human form of the disease.
- Last April, a 2013 Life Science Leader company to watch, CogRx, announced its intention to launch a clinical trial of its Alzheimer’s candidate in 2015. The company is developing small molecule drugs that are designed to keep toxic Abeta oligomer proteins and their receptors from binding to the brain. In pre-clinical trials, the soon-to-be tested drug showed promise in causing the sustained reversal of the disease. The company was also a 2014 recipient of a grant from the National Institute of Aging (NIA)/NIH for the development of its small molecule soluble Abeta receptor antagonist program.
- The NIA launched two trials in early 2014: the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s Disease Trial, or A4 trial, and the Study of Nasal Insulin to Fight Forgetfulness (SNIFF). The NIH-funded A4 trial aims to test Lilly’s solanezumab in 1,000 patients age 70+ that have amyloid in their brains but aren’t showing symptoms of Alzheimer’s. Just this month, in fact, Harvard University began scanning the brains of healthy patients enrolled in the A4 study to identify those whose brains contain the tau protein — a key player along with amyloid in the spread of Alzheimer’s. The SNIFF trial will investigate insulin nasal spray’s effect on memory improvement and preservation in adults 55 to 85 with mild Alzheimer’s disease.
- At the end of 2013, Merck announced it was pushing its BACE-inhibitor candidate, MK-8931, into the Phase 3 EPOCH trial. MK-3981 is being examined in 1,960 patients, with results expected by mid-2017. The company also announced its intentions to test the drug in the Phase 3 APECS trial, enrolling 1,500 patients who do not yet have dementia.
- Mid-2013, Eli Lilly announced its intention to refocus trials for its Alzheimer’s drug solanezumab on patients with milder forms of the disease. In 2012, the drug failed to improve cognition and function in patients with mild to moderate forms of Alzheimer’s. However, in pre-specified secondary subgroup analyses, both of the Phase 3 studies showed the drug significantly slowed cognitive decline in patients with mild forms of the disease. In the newest trial, the company plans to enroll 2,100 participants who have signs of beta amyloid (compared to the previous trials that enrolled 1,300 patients — a quarter of whom did not have beta amyloid and might have been suffering from other forms of dementia).