Are we close to alzheimer’s cure?
The need is great, barriers are many and rewards high- this is the current scenario of Alzheimer’s drug development. It’s been 14 years since the last new drug was approved for Alzheimer’s by the FDA and for long Alzheimer’s disease has been a graveyard f
Improved healthcare facilities, better access to quality health infrastructure and growing awareness of good lifestyle is helping people live longer. Yes, that is good news! But with old age comes age related disorders like dementia that rob elders of their cognitive abilities, severely impacting their day to day life. Today, across geographies, many elderly suffer from disorders that fall under the umbrella term dementia and despite concerted efforts from the scientific community and pharmaceutical industry, researchers have frustratingly failed to develop drugs for some of the most frightening age related diseases. Alzheimer’s is one of the most common type of dementia. Alzheimer’s disease is increasing rapidly in frequency as the world’s population ages and more people enter the major risk bracket for this age-related disorder. From the
5.3 million US citizens affected now, experts predict that the number of victims will increase to 13 million or more by 2050 and worldwide the total number of affected individuals is expected to increase to a staggering 100 million. The cost of care in the US, currently more than $200 billion annually, will grow to an unsupportable $1 trillion annually by 2050.
Alzheimer’s is a neurodegenerative, progressive disease of the brain, which leads to loss of memory and cognitive functions. It also involves parts of the brain which control thought, memory, and language and over time can seriously affect a person’s ability to carry out daily activities. Alzheimer’s accounts for 60-80 per cent of dementia cases. The disease was first discovered in 1906 by Alois Alzheimer and since then, has been difficult to treat. Alzheimer’s is a progressive disease, in which symptoms of the disease gradually worsen over a number of years.
This disease has no current cure; there are drugs that only treat symptoms and these drugs are highly patient dependent.
For the pharma industry, it’s been a bumpy ride to fight Alzheimer’s disease. Alzheimer’s is a formidable foe for a number of reasons. The brain isn’t easy to access, animal models for testing are difficult and it is estimated that nearly 99.6 per cent of the clinical trials have failed in the course of 2002 to 2012. A recent study looked at how 244 compounds in 413 clinical trials fared for Alzheimer’s disease between 2002 and 2012. The study findings paint a gloomy picture. Of those 244 compounds, only one was approved.
Despite this sky-high failure rate, pharmaceutical companies are leaving no stone unturned to find a cure for this debilitating disease, presumably because of the lucrative and largely untapped drug market.
thinks that a medicine for Alzheimer’s could rake in a monstrous $20 billion in sales by 2030, given that over 5 million Americans already suffer from this debilitating disease, combined with the fact that there are no treatments available right now.
In the past decade or two, global drug powerhouses like Eli Lilly, Eisai, Roche, Pfizer, AstraZeneca, Biogen, and Merck have devoted billions of dollars into projects. Among this diverse list of clinical hopefuls, Eli Lilly and Biogen’s betaamyloid plaque-busting antibodies -- solanezumab and aducanumab, respectively -- have garnered the most attention, in part because of the advanced state of their development. While the lucrative market is attracting pharma companies, so is repeated failures and billions of dollars spent, prompting several pharma giants to end their research efforts towards finding a cure for the disease.
2018 began with pharma giant Pfizer announcing that it was ending its internal efforts to develop new drugs for Alzheimer’s and Parkinson’s diseases. Axovant Sciences also announced that it is pulling plug off its Alzheimer’s drug after a key study failure. These setbacks pile on to an already depressing situation: more than 400 failed clinical trials since the last Alzheimer’s drug — which only treats the symptoms of the disease, temporarily — was approved more than a decade ago.
“I was surprised, because I knew Pfizer had interesting compounds in the pipeline,” said Dr. Jeff Cummings, director of the Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas as quoted by the CNBC. For Cummings, though, it was ultimately just one more addition to a long record he has maintained, documenting the failure of Alzheimer’s treatments. “It is another statement that development of drugs, particularly for neurodegenerative diseases like
Alzheimer’s and Parkinson’s, has proven to be enormously difficult.”
It takes on average 13 years for a candidate for Alzheimer’s treatment to move from laboratory to Food and Drug Administration (FDA) review and 10 years for an agent to navigate the clinical development period from start of phase I to end of FDA review, elaborates a recent study. This means that under current circumstances, an agent must now be in phase II to possibly be approved by 2025. Although there are few promising agents in the clinical trial pipeline with the high rate of failure of Alzheimer’s disease drug development, the aim of having a repertoire of agents that could respond comprehensively and individually to a patient’s clinical circumstances within the 2025 timeframe is not easy. Also, Alzheimer’s patients are generally diagnosed in the late stage, mostly due to delayed appearance of symptoms. Hence, developing the early diagnostic devices that can detect the disease early is also a significant challenge.
A new ray of hope
Amid these string of failures and trial closures, comes Japan’s Eisai and Biogen’s announcement bringing in hope to millions of patients. The companies announced positive topline results from the Phase II study with BAN2401, an anti-amyloid beta protofibril antibody, in 856 patients with early Alzheimer’s disease. The study achieved statistical significance on key predefined endpoints evaluating efficacy at 18 months on slowing progression in Alzheimer’s Disease Composite Score and on reduction of amyloid accumulated in the brain as measured using amyloidPET.
“This is the first late-stage anti-amyloid antibody
study to successfully achieve statistically significant results at 18 months, further validating the amyloid hypothesis,” said Lynn Kramer, M.D., Chief Clinical Officer and Chief Medical Officer, Neurology Business Group, Eisai in its press release on July 5. “We will discuss these very encouraging results with regulatory authorities to determine the best path forward. We continue to work towards the goal of delivering BAN2401 to patients and healthcare professionals as early as possible.”
Earlier many pharma giants have also focused on addressing the issue of amyloid protein buildup in Alzheimer’s patients. Many of these clinical trials flopped and this has cast doubt on amyloid hypothesis. The latest results for BAN2401, however, showed improvement on two key fronts. First, the drug slowed progression in Alzheimer’s disease by a statistically significant amount. Second, it reduced the amount of amyloid accumulated in the brains of patients by a statistically significant amount.
This aside, the more promising late-stage Alzheimer’s disease drug for Biogen is aducanumab, which it is co-developing with Neurimmune Holding. Biogen has three candidates in phase 3 clinical testing. Two of them, like BAN2401, target the treatment of Alzheimer’s disease. And both, also like BAN2401, seek to reduce amyloid accumulation in the brain. Aducanumab ranked third on market research firm EvaluatePharma’s list of top pipeline assets in the biopharmaceutical industry.
Huge untapped market
Statisticians estimate that more than 2 billion people will be above 60 years by 2026. Rising old age population and higher incidences of neurodegenerative diseases are two significant factors that supplement the market growth. Moreover, increasing R&D investment, global initiatives and encouragement to find a cure for Alzheimer’s is further expected to fuel the market growth.
A recent market report suggests that global Alzheimer’s drugs market was valued at approximately $3.42 billion in 2016 and is expected to generate revenue of around $5.09 billion by end of 2022, growing at a CAGR of around 8 per cent between 2017 and 2022.
Alzheimer’s is one of the leading causes of death in the United States. The huge disease burden with very few therapeutic alternatives indicates an impending market need that would provide lucrative growth opportunities to the industry players.
Asia Pacific is also a key market for Alzheimer’s interventions. Growth in Asia Pacific market is expected to be driven due to growing awareness about the treatment of Alzheimer’s in the region.
This region is likely to be a key contributor to the global Alzheimer’s drugs market in the coming years. Some of the key players in Alzheimer’s Drugs are Ono Pharmaceutical, Johnson & Johnson, Daiichi Sankyo, H Lundbeck A/S, Eisai, and among others.
Global Data analyst Tom Moore thinks that Biogen’s BAN2401 could generate peak annual sales of more than $1 billion if it earns FDA approval. Hence, though the risks, funding challenges and barriers for companies working in Alzheimer’s are huge, but so too, potentially, are the rewards.