Which pharmaceutical company will produce the blockbuster treatment for Alzheimer’s disease? Alzheimer's, which involves the degeneration of connections between brain cells and subsequent loss of cognitive functions, affects approximately 5.4 million people in the United States. Alzheimer's kills half a million each year and does not have an effective treatment option.
Top pharmaceutical companies like J&J, Pfizer, and Eli Lilly have endured multiple failures in Phase III trials for Alzheimer's drugs. Drug trials for Alzheimer's often fail because there is no way of detecting Alzheimer's until symptoms arise. At this point, it is too late to halt problematic brain processes associated with Alzheimer's. Current FDA-approved treatments for AD tackle symptoms but not the underlying causes and thus are unable to slow the progression of the disease.
Scientists have shown that people with Alzheimer’s have abnormal clusters in their brains, referred to as Ab. Many companies attempting to create treatments for Alzheimer's, including some discussed below, are searching for ways to disrupt Ab by preventing its formation or attacking Ab once it’s formed.
Alzheimer's Drug Testing and Treatment History
The United States alone spent $214 billion in 2014 to provide health care for Alzheimer's disease. Though this spending is indicative of a substantial market for an effective treatment, the number of clinical trials has decreased in recent years.
Even the NIH invests relatively little in Alzheimer's drug testing, spending about $600 million per year on the disease, or about one tenth of the NIH's budgets for cancer treatments. Much of the investment burden falls to pharmaceutical companies and private investors who fund the research and development required to develop and commercialize Alzheimer's treatments.
Large Pharmaceuticals Developing Alzheimer's Treatments
Despite repeated failures in clinical trials, leading pharmaceutical companies continue to invest time and capital in finding Alzheimer's treatments. However, these pharmaceutical companies appear to be shifting their strategy as they collaborate more with other large pharmaceuticals and small startups.
Following mixed results for a clinical trial testing of an Ab antibody by AC Immune and partner Genentech (a Roche subsidiary), AC Immune entered a separate partnership with Johnson & Johnson. Together, J&J and the Swiss biotech company will boost R&D around ACI-35, a vaccine against tau, another key protein in Alzheimer's. Investing in the anti-tau vaccine could benefit J&J, as other companies continue to focus on targeting Ab. The vaccine is in a Phase 1b clinical trial where the vaccine is being tested for its ability to stimulate the immune system to attack tau.
Pfizer’s current Alzheimer's strategy is to partner with Alzheimer's experts. Pfizer's Centers for Therapeutic Innovation (CTI) is collaborating with the Alzheimer’s Drug Discovery Foundation (ADDF) to invest in translational research aimed at developing small molecule drugs for Alzheimer's. By providing researchers with joint funding, and the resources and expertise from both groups, CTI and ADDF hope to hasten the generation of effective drugs. The agreement with ADDF may position Pfizer to better identify promising lines of research and invest accordingly.
Eli Lilly is teaming up with AstraZeneca to attempt to commercialize AZD3293, which is a beta secretase cleaving enzyme (BACE) inhibitor that may be capable of preventing the Ab formation that is observed in Alzheimer's. Phase I trials demonstrated the ability of an oral BACE inhibitor to reduce the amount of Ab, in both Alzheimer’s patients and healthy volunteers. Phase II/III trials are underway. Showing that AZD3293 leads to cognitive improvements will be critical to the drug’s success.
Biogen has demonstrated that its antibody against Ab, BIIB3037, can lead to cognitive improvements in people with early Alzheimer's signs. In a Phase 1 trial designed to test the compound's safety, researchers were encouraged to find that BIIB3037 also demonstrated efficacy: BIIB3037 reduced the levels of Ab in the brain, and higher BIIB3037 doses led to lower Ab levels. Though Biogen could see similar frustrating outcomes in Phase III trials, Biogen's Phase 1b data is so promising that Biogen is moving directly to Phase III.
Alzheimer's Emerging Therapeutic Companies
Some smaller companies are braving the Alzheimer’s field and may make significant contributions for intervening in the deadly disease. A couple favorites are:
Alzheon is a clinical-stage biotechnology company focused on brain health, memory and aging, developing transformative treatments for Alzheimer’s disease and other neurodegenerative disorders. Alzheon raised $10 million in Series A funding in April 2015. The funding was meant for Phase III clinical studies for a therapy promising to improve Alzhemer's patients' function and cognition.
Pharnext is a privately owned French company combining drugs to target multiple disease pathways and produce synergistic effects. In February 2015, Pharnext published results on its Alzheimer’s drug, PXT-864, showing that this drug produces beneficial effects in rodent models of the disease. PXT-864 is a combination of baclofen and acamprosate, which are often used to treat multiple sclerosis and alcoholism, respectively. The preclinical data suggest that the positive effects of the drug on both the brain and cognition are greater than could be expected by simply adding the known effects of each of the component drugs.
Axxam SpA received a $340,485 grant from ADDF in January 2015 to develop a small molecule treatment targeting brain inflammation. This Italian biotech company will apply the grant funds toward identifying ways to selectively block P2X7, which is a brain receptor associated with inflammation. Though effectively reducing inflammation could certainly minimize problems associated with Alzheimer's, reducing inflammation is not likely to cure the disease because such an approach does not target the developmental processes that underlie Alzheimer's.
Gismo Therapeutics, a biotech startup, is a newcomer to watch. Gismo's technology is based on the idea that amyloid (the ‘A’ in Ab) must interact with other molecules to become toxic. Gismo's aim is to prevent the types of molecular interactions that lead to Alzheimer's. In addition to filing for its first patent in January 2015, Gismo has also landed a highly competitive SBIR grant from the NIH, as well as additional funding from places like the Michael J. Fox Foundation.
Alzheimer's Emerging Non-Therapeutic Companies
The significant challenge researchers have faced in developing effective drugs to treat Alzheimer’s disease has opened up market opportunities for companies that can facilitate development efforts.
Amarantus has created a blood test, LymPro, to identify biomarkers for Alzheimer's. In addition to the clinical benefit of enabling physicians to diagnose Alzheimer's earlier and with more confidence, LymPro can add significant value in Alzheimer's research. Amarantus may thus become a major provider for pharmaceutical companies interested in testing the effects of their candidate drugs. Of particular interest will be recruiting subjects that have not been diagnosed with AD but are likely to be diagnosed in the coming years.
The success of Amarantus' blood test has led to multiple funding rounds in the past two years, including $1.3 million in October 2013 and an additional $3 million in November 2014:
Amarantus has an exclusive agreement with Georgetown University to commercialize biomarkers and will offer the pharmaceutical industry access to its biomarkers. This week, Amarantus announced its first collaboration. Amarantus will work with Anavex Life Sciences Corp. (AVXL) to test the ability of Anavex prouducts to affect specific AD markers.
Neurotrack spun out from Emory University in 2012 and, like the LymPro test, Neurotrack addresses the limitations imposed by the inability to detect Alzheimer's early. Neurotrack uses an eye-tracking assessment that can apparently detect the risk of developing Alzheimer's 3 to 6 years before symptoms begin. This technology has many of the same advantages of LymPro but provides a less invasive, relatively inexpensive and simple way to identify Alzheimer's pre-symptomatically.
Protea has produced Laser Ablation Electrospray Ionization (LAESI), which is a bioanalytics technology that facilitates the identification of key Alzheimer's molecules. Unlike other technologies that analyze the molecular makeup of tissues, LAESI requires minimal tissue processing and thus provides a relatively easy way to generate large data sets that enable efficient identification of Alzheimer's biomarkers and candidates for drug targets.
Yumanity launched in December 2014 in a partnership between Susan Lindquist, 2009 winner of the National Medal of Science, and Tony Coles, former CEO of Onyx Pharmaceuticals. Yumanity will focus on protein misfolding, which occurs when amino acid strands incorrectly form functional proteins.
Cortexyme is a Peter Thiel-backed biotech developing a small-molecule treatment related to a specific (undisclosed) pathogen tied to Alzheimer’s.
Alector is leveraging recent discoveries in neuroimmunology and human genetics data to develop antibody drugs aimed at genetic-based targets for Alzheimer’s. Alector raised an undisclosed amount of funding in October 2013 and struck a deal with J&J’s Innovation Center to fund early research and development efforts.
Future of Alzheimer's Treatments
Recent developments promising earlier detection of Alzheimer's were bolstered by a new finding published in February 2015 by scientists at Cambridge. The researchers reported in Nature Structural and Molecular Biology that they were able to prevent the development of Ab using brichos, a molecule known as a molecular chaperone. Specifically, the scientists showed that brichos binds to the amyloid fibers that cluster to form Ab (i.e. preventing them from sticking together). Though brichos itself would not be an effective intervention because the body would likely absorb it before it could enter the brain, the findings are encouraging because they suggest that Ab formation could be prevented.
Many researchers and physicians believe that an effective AD treatment will be a cocktail of drugs, much like treatments used in cancer and HIV. There are thus many players in the game, and continued collaboration may be the key to finding a cure for the disease. In the meantime, the companies offering tools that help clarify the etiology of Alzheimer's and the potential impact of different therapeutics are the ones likely to dominate the relevant market.
About the Writer
Nisha Kaul Cooch is the founder of BioInnovation Consulting LLC, a life sciences communications firm based in Washington DC. Dr. Cooch holds a PhD in neuroscience and specializes in the intersection of technology and decision making. You can follow her on Twitter @BioInnovationCo.