Three years ago, my grandfather died. At the age of 89 years old some might say that was a long life lived. But for the best part of his last decade my grandfather suffered with escalating dementia, the most common cause of which is Alzheimer's disease.
The word dementia describes a set of symptoms that include memory loss and difficulties with thinking, problem-solving or language. These symptoms occur when the brain is damaged by certain diseases, including Alzheimer's. More than half a million people in the UK suffer with Alzheimer's disease. During the course of the disease, proteins build up in the brain to form structures called 'plaques' and 'tangles'. This causes a loss of connection between nerve cells and, eventually, the death of nerve cells and loss of brain tissue. Alzheimer's patients can also have a shortage of the important chemicals that transmit signals around their brain. When there is a shortage of these chemicals, the signals are not transmitted as effectively.
I, like many others, have had first-hand experience of watching this disease rob people of their golden years. I watched my grandparent - the reigning patriarch of our family - lose his memories, bearings and, at the end, recognition of my grandmother to whom he had been married since 1945. It has been said that Alzheimer's is the biggest concern for people over 50, beating cancer, heart disease or any other terminal diseases, mainly because Alzheimer's is not only distressing for the patient but for their nearest and dearest who are forced to watch the person they love disappear before them. Eventually, ordinary people, without specific training and often elderly themselves, are left caring for an empty shell.
The Alzheimer's Society says the disease is most prevalent among over 65s. Above this age, a person's risk of developing Alzheimer's disease doubles approximately every five years. And while the reason remains unknown, about twice as many women as men over 65 fall victim to the illness. So far, the only explanation appears to be the lack of the hormone oestrogen after menopause. But most frightening is the possibility of what professionals call "early-onset" Alzheimer's where symptoms of the disease start showing up in people younger than 65. Medical advances to extend life expectancy, coupled with the slow, degenerative nature of Alzheimer's means some people will spend the second half of their life succumbing to an irreversible and lonely fate.
Elusive treatments
It's no surprise, therefore, that the healthcare industry has made a cure for Alzheimer's a top priority, along with cancer and HIV. Only earlier this month, hopes were raised by a study conducted by researchers from several Gladstone Institutes in San Francisco, the University of California, Stanford University School of Medicine and the Buck Institute for Research on Aging. They tested an existing arthritis drug called Salsalate on mice with clumps of tau (plaque) in their brains. Salsalate was found to block the process that can lead to a further protein build-up. Treated mice also performed better in tests designed to assess memory skills.
These findings are promising, but human studies will be required to determine how effective the drug is and over what timescale. But - as the NHS has pointed out - because this drug has already been approved for use in humans (albeit for arthritis) the relevant tests may come sooner rather than later. In the meantime, health professionals are urging no one take Salsalate as a treatment for Alzheimer's - especially as it has been shown to be dangerous in patients recovering from heart surgery.
Acetylcholinesterase inhibitors (known more commonly as donepezil, rivastigmine and galantamine) and memantine are the only drugs currently approved for the management of Alzheimer's. And management is a crucial word. These drugs only provide modest symptomatic improvement and do even less to modify the disease process, far less reverse it completely. They haven't proved effective in the treatment of all kinds of dementia, either. Donepezil was originally patented under the brand name Aricept, but is more widely available now as just generic donepezil. Rivastigmine was patented as Exelon and is now also available as other brands, as well as generic rivastigmine. Galantamine was patented as Reminyl and is now also available as generic galantamine and the brands Reminyl XL, Acumor XL, Galsya XL and Gatalin XL. Memantine was originally patented as Ebixa and is now also available as generic memantine. Other UK brand names for memantine include Maruxa and Nemdatine.
Crucially, there are no treatments that can cure Alzheimer's disease or any other common type of dementia. Instead, the major developments in this direction are amyloid and tau-based therapeutics, which could hold the key to Alzheimer's treatment in the future.
No new drugs have been licensed in the UK for Alzheimer's disease since 2002-03, so there's a huge growth opportunity for drugs companies looking to create effective Alzheimer's treatments. But the Dementia Forum of the World Innovation Summit for Health has warned that a "history of failures" has created "funding fatigue" among big pharma companies. According to the report, major drug companies halved the number of research programmes into central nervous system disorders, including dementia, between 2009 and 2014. Dr James Pickett, head of research at the Alzheimer's Society, believes public-private partnerships are the answer, as they're designed to share the risk of investment for future funding of research.
BCC Research has said the Alzheimer's market will be worth $9.5bn in 2017. That's actually down from the $10.2bn it claims was spent on Alzheimer's in 2012, but it doesn't reflect a drop-off in the need for new treatments. In fact, it reflects the expiry of several patents for existing Alzheimer's drugs - so the need for innovation is even clearer.
Inching closer
But it's not true to say big pharma has given up hope completely. Earlier this year US giant Eli Lilly (US:LLY) revealed encouraging clinical trial data on its drug solanezumab. Eli Lilly hopes solanezumab can help slow the pace of mild Alzheimer's by up to 34 per cent - thus decreasing the financial burden on society by allowing patients to remain independent for longer. It could also deliver a multibillion-dollar windfall for the company's investors if successful. More results are needed to corroborate these findings, but data could be due as soon as late 2016, and an official drug approval could come within three years barring any significant clinical setbacks.
It's not just Eli Lilly that wants to be responsible for the frontline in fighting Alzheimer's. US group Amgen (US:AMGN) has agreed to help Swiss giant Novartis (US:NVS) develop its pipeline of Alzheimer's drugs by paying an upfront fee, further milestone payments and the majority of research and development (R&D) costs. In return, the two companies will split profits of successful drugs equally.
The IPO of US biotechnology company Axovant (US:AXON) also made headlines earlier this year. The company only has one undeveloped drug to its name - a prospective treatment for Alzheimer's called RVT-101 bought for $5m from GlaxoSmithKline (GSK) in December 2014 - but priced its shares at $15 a share at the time of the float, raising $315m in the process, and snaring a market capitalisation of more than $2bn. Since then, the shares peaked at more than double that listing price, but have reverted to a mere $13 apiece as fears of a biotech bubble gathered pace over the summer.
That could all be about to change - again. In October 2015, the group revealed it had started a final-phase clinical trial of RVT-101 in 1,000 patients with a mild to moderate form of the disease in combination with Aricept, an existing Alzheimer's medicine. The first results are due in 2017 and regulatory approval from the US Food and Drug Administration (FDA) could follow in 2018 if the data proves successful. GSK previously shelved the compound after it failed four clinical trials involving more than 1,800 patients, before hiving it off to Axovant for a bargain price. But supporters of the possible drug claim GSK only threw the drug on the scrapheap as a result of extensive cost-cutting. If Axovant can get the product to market, GSK is still set to earn close to 13 per cent in royalties on future sales.
Axovant is different for other reasons, too. It was founded by 29-year old Vivek Ramaswamy, who said he intends to use the IPO proceeds to acquire other potential Alzheimer's drugs, in turn developing the world's largest "dementia solutions company".
Fellow US biotech group Biogen is bound to be a close competitor to Axovant. In March, it announced positive results from clinical trials of its potential Alzheimer's drug, aducanumab. Some criticised the study for inciting too much excitement too soon (the sample population size was less than 200 people) and there are concerns about the range of side effects associated with taking the treatment. But just these initial findings alone have been more than 25 years in the making. The difference, compared with finding treatments for cancer for example, is trying to keep certain cells alive instead of killing them off. Pros and cons aside, the results were deemed sufficiently compelling for Swiss giant Roche to take another look at data it had previously shelved on future Alzheimer's medicines.
Value creation
Finding a cure or even an effective treatment for Alzheimer's could unlock significant value for shareholders. Shares in Eli Lilly are still trading close to a 12-month high, having peaked at $92 in September 2015. And the warm reception from Wall Street to the Axovant float is a prime example of biotech bulls at their best. But sceptics are quick to remind investors that there has been no significant breakthrough - no biotech frontiers smashed, no new therapies or ways to use the human body to tackle the disease. So far, it's simply a case of rehashing existing science. It's also worth remembering that between 2002 and 2012, it's thought roughly 99 per cent of clinical trials based on testing potential Alzheimer's drugs ended in failure.
Encouragingly, the UK government - along with several large pharmaceutical companies - aren't giving up hope. The Dementia Discovery Fund (DDF), a global investment fund to support discovery and development of new dementia treatments has just launched, raising $100m from investors, including Department of Health and Alzheimer's Research UK, alongside Biogen, GlaxoSmithKline, Johnson & Johnson, Eli Lilly, Pfizer and Takeda. Managing the fund is life sciences venture capital firm SV Life Sciences.
The new vehicle has put a timeline on itself to come up with new approaches to treating the disease by 2025, although the word 'cure' has not made itself into the manifesto. Instead, the fund says it will aim to find drugs that could improve symptoms or "modify the course of disease". Kate Bingham, managing partner of SV Life Sciences, has said developing new treatments for dementia is "hugely important" but also "enormously challenging". She also admitted that those drugs on the market all address symptoms but have "no effect on the underlying disease". Patrick Vallance, president of the pharmaceuticals R&D division at GSK, concurs: "This is a complex and costly area of research", but if drugs companies, research institutions and governments "work together and jointly shoulder the risk" an effective treatment is possible.
Dr Dennis Gillings, the UK government-appointed World Dementia Envoy, has said dementia is "a ticking bomb" and with the global cost of dementia care expected to exceed $1 trillion by 2030 more must be done to combat the roots of the disease. Research, he says, is "not delivering results" and there are "serious economic and social impacts" if this "critical global health issue" isn't tackled. Pharmaceuticals companies are racing against time, but investors putting money into various projects are almost certain to reap the reward if anything resembling a cure or symptom-reversing drug is proved to work.
Finding the cure: cancer – an expert response Congratulations on your article “Finding the cure” in the 14 August 2015 edition of Investors Chronicle. I have been involved in cancer research and management as a surgical oncologist for over 50 years. I believe the following observations will help other readers with an interest in investing in those companies exploring cancer treatments. I trust these factors will help readers understand why regular press items speaking of an “imminent cancer breakthrough” do not impress seasoned practitioners. Yours sincerely FD Skidmore OBE MA MD FRCS Consultant Surgeon & Surgical Oncologist Cancer facts and economics: 1. The term cancer indicates tumours arising from the inner lining of body cavities and ducts. These tumours of the lung, gastrointestinal tract and genito-urinary tract as well as skin relate to environmental factors such as smoking, sunburn and infection, eg papilloma virus, HIV/AIDS and gastric helicobacter. They are all characterised by a long interval between exposure and malignant change. 2. Other epithelial cancers such as those that develop in the ovary, pancreas and prostate develop silently and often present late when they have spread/metastasised. There are inheritance factors such as colon polyposis and BRCA1 breast cancers which are more common in communities with consanguinity. 3. Populations internationally are reluctant to accept this well-meaning evidence and advice from medical scientists about the risks of practices which we know promote cancer – the best example of this is cigarette smoking and lung cancer, but there are also enhanced risks of larynx, pharynx and bladder tumour from tar inhalation. Pipe tobacco and snuff promote oropharyngeal cancers, alcohol enhances the risk of pancreatic and oesophageal tumours and obesity is a factor in breast, oesophagus and bowel cancer. Notwithstanding this evidence populations most at risk of these problems are the least willing to accept screening tests even when these are provided free by governments. 4. There are a series of other tumours such as sarcoma, brain, lymphoreticular and embryonic tumours which are rare and basically we still have no idea why the majority of these suddenly occur. 5. There are national dietary factors, such as the high propensity of the Japanese to develop oesophago-gastric carcinomas. This has resulted in medico-industrial cooperation thus leaving Japan as a world leader in endoscopy for body cavity inspection and biopsy. 6. By contrast, Europe, North America and the British Commonwealth have the highest incidence of breast, gastrointestinal, lung and genito-urinary tumours and produce the best (surgery, chemotherapy, radiotherapy, etc) composite treatment regimes. 7. Unfortunately comorbidities are common, the most prevalent being age related, and these can prevent aggressive treatment. Obesity, diabetes, chronic pulmonary disease and cardiovascular insufficiency alone or in combination can all prevent us optimising treatment in an attempt to provide best prognosis for the patient. 8. Research implication: the flashes of scientific intuition which guided Fleming in the 1940s or Watson/Crick in the 1950s are rare. The practical economics of big pharmaceutical companies either with ‘in-house’ research or imported evidence from university studies mean that when a promising advance appears they have to commence phase I, II, and III trials and accommodate rigorous FDA evaluation all of which increases amortised production costs. 9. In the UK, the National Institute for Health and Care Excellence recommendations and quality of life expectancy are all political rather than ethical scientific and clinical factors which determine whether a particular product will come to be used in a financially constrained NHS. |
