One of the burning topics that industry and academic scientists, policymakers and patients will be discussing this week at a one-day forum focused on the primary hurdles to combating Alzheimer’s disease (AD), sponsored by the Pharmaceutical Research and Manufacturers of America, the Alzheimer’s Association and the Alzheimer’s Drug Discovery Foundation, will be how to accelerate the impact of pre-competitive collaborative partnerships to get products moving into clinical trials.

The topic is a timely one because companies and research organizations alike are beginning to recognize the need that collaboration is a necessary requirement in order to improve research on innovative products to prevent Alzheimer’s disease. It certainly appears that the penny is starting to drop because several big pharmaceutical companies have joined together with major international companies as founding members of Washington D.C.-based Global CEO Initiative on Alzheimer’s disease (CEOi).

The organization’s goal is to create a clear pathway to diagnose, prevent and treat Alzheimer’s by 2025, and members such as Eli Lilly and Co., Janssen Pharmaceuticals Inc., Merck & Co. Inc., Pfizer Inc., Sanofi SA and GE Healthcare, are lending their resources and expertise to ensure this becomes a reality.

Big Data

One of their initiatives is the Alzheimer’s disease Big Data Challenge – an effort to increase innovation and identify new AD biomarkers through the use of open source data from Alzheimer’s patients provided by the Alzheimer’s disease Neuroimaging Initiative (ADNI), which consists of cognitive, imaging, biochemical, and whole genome sequencing data. CEOi is joining with Sage Bionetworks to co-lead the challenge.

The winning predictive model from the challenge will be determined by evaluation against a similarly structured validation data set that is either newly generated for the challenge or not yet released. The participants will be evaluated by an independent, scientific advisory board that will award the model that best predicts cognitive scores using ADNI and outside data. The winners of the challenge will be announced in 2014.

The development of new Alzheimer’s biomarkers would certainly help researchers better identify AD early on and potentially open new doors to therapy and treatments.

“There are currently no disease modifying cures or treatments for Alzheimer’s disease, which speaks to the dire need to develop new biomarkers,” said Alex Gorsky, CEO of Johnson & Johnson, in an announcement about the challenge. “These biomarkers could serve as an invaluable tool to the research community, especially at a time when current levels of funding are low.”

The push for earlier diagnosis is important because the “seeds” of AD are planted early and by the time it manifests itself clinically the “roots” are deep and difficult to treat.

New tools, particularly amyloid-imaging agents, such as recently launched Amyvid (florbetapir) from Lilly subsidiary Avid Radiopharmaceuticals Inc., which the company acquired three years ago, should help detect AD sooner There are several potential positron emission tomography (PET) imaging agents in clinical trials that researchers hope will help with diagnosis by identifying beta amyloid plaques in the brain early in AD.

Navidea Biopharmaceuticals Inc., of Dublin, Ohio, for example, has its NAV4694 beta amyloid imaging agent in late-stage trials. The company recently received a Small Business Innovation Research grant from the National Institute on Aging in connection with the development of the agent, which will partially support a Phase IIb trial evaluating NAV4694 as a diagnostic imaging agent that may aid physicians in identifying those individuals with mild cognitive impairment who are at greatest risk of progressing to Alzheimer’s disease. (See BioWorld Today, Sept. 5, 2013.)

Diagenic ASA, of Oslo, Norway, is collaborating with GE Healthcare, of Princeton, N.J., to develop a blood-based test using Diagenic’s peripheral gene expression profiling in patients with mild cognitive impairment, a disorder associated with risk for AD. The study would be used in conjunction with PET imaging to identify a blood based gene expression signature in these patients. The PET imaging agent [18F] flutemetamol is being developed by GE Healthcare.

Merck, of Whitehouse Station, N.J., is also collaborating with GE Healthcare for the use of [18F] flutemetamol to support development of MK-8931, an oral, beta amyloid precursor protein site cleaving enzyme inhibitor in development for AD. (See BioWorld Today, Dec. 19, 2012.)

A Full Pipeline

The later-stage pipeline for candidate therapies targeting AD is certainly robust. According to Cortellis Clinical Trials Intelligence, a database developed by BioWorld’s parent Thomson Reuters, there are 95 Phase II clinical trial studies in active recruitment and 56 trials for products at the Phase III stage.

Among the medicines in development is a Phase II study of CERE-110 (AAV-NGF), a gene therapy product designed to deliver nerve growth factor (NGF) for the treatment of AD. The product was being developed by San Diego-based Ceregene Inc. but the asset was taken over by Sangamo Biosciences Inc., of Richmond, Calif., which acquired the company in August. (See BioWorld Today, Aug. 28, 2013.)

H. Lundbeck A/S, of Valby, Denmark, and Otsuka Pharmaceutical Co. Ltd., of Tokyo, recently initiated the first of four planned Phase III trials of Lu AE58054 to treat AD. The trial will study the effect of several doses of the selective 5HT6 receptor antagonist, ranging from 10 mg to 60 mg, in combination with donepezil in mild to moderate AD as adjunctive therapy to acetylcholinesterase inhibitors. The companies said the Phase III program will enroll approximately 3,000 patients worldwide and the trials are expected to last up to three years. (See BioWorld Today, Oct. 16, 2013.)

Masitinib, a tyrosine kinase inhibitor (TKI) being developed by AB Science SA, entered a 400-patient Phase III trial in Alzheimer’s, following a Phase II study which indicated that the drug improved cognition and memory in patients with mild to moderate disease. (See BioWorld Today, May 22, 2013.)

Undaunted by an earlier trial disappointment, Eli Lilly and Co. announced that it is making another run at AD with its Phase III candidate solanezumab (sola), this time in the mild form of the disease.

Last year, the drug missed both the cognitive and functional endpoints in its two double-blind, placebo-controlled EXPEDITION trials in patients with mild to moderate disease. The monoclonal antibody binds specifically to soluble amyloid beta and is aimed at drawing the peptide away from the brain through the blood. (See BioWorld Today, July 15, 2013.)

EXPEDITION3 is based on a pre-specified secondary analysis of pooled data across the first two EXPEDITION trials that showed statistically significant slowing of cognitive decline in the overall study population. The trial will include 2,100 patients ages 55 to 90 with mild AD.

In March Taurx Pharmaceuticals Ltd., of Singapore, received an equity investment of $10.5 million from Dundee Corp., of Toronto, to support Phase III trials of LMTX, a tau aggregation inhibitor for AD and behavioral-variant fronto-temporal dementia. Dundee originally invested $20 million in Taurx in September 2011. With the investment, Dundee maintains 5 percent interest in Taurx.

LMTX aims to stop the binding of normal tau protein to neuronal waste products, and the self-aggregating that follows, allowing the toxic material to grow and destroy neurons. The idea is that tau trouble starts AD, and plaque confirms the presence of the condition. The Phase III program will include a study in 833 people with mild to moderate AD over 12 months.