The Past, Present and Future of Alzheimer’s Treatments By Leo Sun - August 19, 2013
Alzheimer’s disease, the most common form of dementia, is one of the greatest medical mysteries of our day. 5.2 million Americans are diagnosed with this debilitating disease, which is the sixth leading cause of death in the country. Alzheimer’s disease usually occurs in patients over 65 years old, and is expected to affect one in every 85 people in the world by 2050 -- a startling figure considering that scientists still don’t fully understand what causes the disease. Those factors make the race to bring a real treatment for Alzheimer’s disease a top priority for the biotech industry. Let’s take a look at the past, present and future of these treatments to better understand the challenges that patients, scientists and biotech investors face.
Current treatments
The current market for Alzheimer’s treatments generates roughly $20 billion in revenue annually, according to Deutsche Bank. However, these treatments only treat the main symptoms of Alzheimer’s -- memory loss, confusion, and cognitive problems -- rather than the actual cause. Aricept, developed by Eisai and Pfizer (NYSE: PFE), is the most popular of these treatments. Aricept is a cholinesterase inhibitor which prevents the breakdown of acetylcholine, a chemical messenger needed for learning and memory. By keeping acetylcholine levels elevated, Alzheimer’s symptoms can be held at bay for an average of six to twelve months in roughly half of the patients. Aricept had peak sales of $2.4 billion in 2010, but have fallen dramatically over the past three years after its patent expiration. Today, generic Aricept is widely available from generics companies such as Actavis and Teva Pharmaceutical. Namenda, which was first synthesized by Eli Lilly & Co. (NYSE: LLY) in 1968, is another common treatment for Alzheimer’s disease. Namenda attempts to protect the brain’s nerve cells against glutamate, a chemical messenger which is released in excess amounts by cells damaged by Alzheimer’s disease and other neurological disorders. If glutamate binds to a patient’s brain cells, it allows calcium to freely enter the cells, causing cell degeneration. Namenda is currently manufactured by Forest Pharmaceuticals, a subsidiary of Forest Laboratories (NYSE: FRX). Last quarter, sales of Namenda rose 7.9% year-on-year to $397.5 million, accounting for 48% of Forest Laboratories’ top line. However, the patent for Namenda expires in 2015, which could send Forest over the edge of the cliff as generics enter the market.
The brain plaque problem
To treat the root cause of Alzheimer’s, scientists are currently working on the theory of brain plaques -- extracellular deposits of beta amyloid in the gray matter of the brain. These brain plaques are believed to be neurotoxic and a major cause of the primary symptoms of dementia. The quest to clear away the plaque, however, has not been an easy one. Pfizer, along with Johnson & Johnson (NYSE: JNJ) and Elan Corporation (recently acquired by Perrigo Company), initially approached this problem with a plaque-clearing humanized monoclonal antibody known as bapineuzumab. Bapineuzumab attempts to use monoclonal antibodies to bind to beta amyloids directly to clear them individually. However, bapineuzumab was shown to be ineffective in patients with mild to moderate Alzheimer’s disease. Development of an intravenous formulation of the drug was halted last August, and a Phase II subcutaneous formulation of the drug was discontinued in July. Eli Lilly, on the other hand, has been working a different angle with its experimental drug, solanezumab -- a BACE inhibitor which seeks to block the creation of beta amyloid deposits altogether, rather than simply clearing them out. However, Lilly hit a major roadblock last year when its experimental drug, solanezumab, showed poor efficacy on advanced Alzheimer’s patients in Phase III trials. Rather than give up as its peers have done, Lilly went back to the drawing board by focusing the treatment on mild Alzheimer’s cases instead, on a larger group of 2,100 patients, compared to the 1,300 in its original trial. Lilly faces some tough competition going forward. Merck and AstraZeneca are also developing BACE inhibitors like solanezumab, and Merck has already presented positive results for its Phase Ib study of its drug, MK-8931.
Smaller competitors at the gates
Big Pharma is not alone in its quest to uncover the elusive treatment for Alzheimer’s. Last year, over 1,000 clinical trials were conducted to test various methods of treating the disease. Many of these trials were conducted by smaller, developmental stage companies, like Prana Biotechnology (NASDAQ: PRAN). Prana’s lead drug, PBT2, is a copper/zinc ionophore which was shown to restore cognition in animal models of Alzheimer’s disease. The drug targets the zinc and copper ions that are necessary for the assembly of the beta amyloid deposits, diffusing them and effectively detoxifying them. PBT2 is currently in Phase IIb clinical studies for Alzheimer’s and Phase IIa clinical trials for Huntington’s disease, a neurodegenerative genetic disorder. The full results from the Alzheimer’s trial will be released in October, and the results of the Huntington’s trial will be available next March. Although Prana is a small fish in a sea of much larger competitors, its progress with PBT2 makes it one of the more important names to watch in the race to treat Alzheimer’s.
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