BANGKOK – A Big Pharma star player – Sanofi Aventis – has been battling a stock market tsunami these past few days. It was all caused by a negative rumor about one of its best-selling products, Lantus (or glargine) – an insulin-a-day wonder that is key in the fight against diabetes.
Tens of thousands of Lantus users panicked. Diabetes is a complex disease with multiple angles, touching tens of millions of people around the world. The stakes – strategic, financial and in terms of health – are enormous. Welcome to the New Health Great Game.
Asia is getting fat. Literally. And that spells trouble. The best specialists agree that obesity is largely responsible for a global diabetes epidemic. For instance, 25% of China’s 1.3 billion people are already overweight. 2.8% of Chinese males and 5% of females are obese; and no less than 16.1% of males and 37% of females suffer from what is graciously defined as “abdominal obesity”. In a nation of no less than 350 million smokers, 60% of them males, and with female smoking also rising, that spells a monster red alert.
By 2025, no less than 20 million people all over the world will be dying of cardiovascular diseases – mainly coronary diseases and strokes, linked to a cluster of risk factors that include obesity. And this will especially affect low and middle-income countries, as are most in Asia.
The medical diagnosis is implacable, as presented by Professor Rody Sy, of the University of the Philippines. “Carbohydrates in excess of energy needs” lead to “abdominal obesity”, and that causes “dyslipidemia [major alterations in cholesterol traffic], hypertension and diabetes”. This carbohydrate-rich diet may be better handled in rural areas, where people move about more often; but in increasingly urbanized – and sedentary – Asia it can be lethal. What to do about it?
In November 2008, in New Orleans, a group of global specialists from North America, Europe and Asia launched the Residual Risk Reduction initiative (known in the industry as R3i). That was packaged as a global program to reduce excess risk of myocardial strokes, kidney diseases, loss of vision and even non-traumatic limb amputation that afflict millions of people with diabetes – even those currently under available medication. R3i has just hit Bangkok, via a conference/workshop designed to spread the wake-up call to doctors from all over Asia.
Statin therapy is the current ABC in the treatment of cholesterol alterations. As specialists describe it, for the past few decades the treatment with statin of vascular risk associated with “lipid disorders” had only dealt with “bad cholesterol”. It’s time to take on “good cholesterol” as well.
Taxi to the cholesterol side
Cholesterol is an essential raw material for cells to work properly. As medical news analyst Dr Jean-Philippe Minart explains it, cholesterol is delivered by an army of “taxis” along a network of highways – the arteries.
Among these taxis, a major transportation company stands out: the LDL-cholesterol. They deliver their content to the artery walls. Then scores of trash-carrying trucks come to recover cholesterol from the artery walls, thus preventing their accumulation: these are the HDL-cholesterol transporters.
So we have on one side transporters that screw up and make a mess out of it sometimes, the LDL or “bad cholesterol”; and the cleaners, the HDL or “good cholesterol”. But this is not about good and evil; the point is that cholesterol should not pile up in the wrong place. It’s gotta move all the time.
Coming from our food intake, cholesterol is always in transit. As soon as it’s absorbed by our stomach and refined by a factory – our liver – it’s transported by the army of taxis along our vessels and to our cells, all of them voracious consumers. If we have too much cholesterol, the number of LDL taxis is higher, cholesterol shoots up and piles up in the artery walls: that’s atherosclerosis. Circulation is at risk, and we face a lethal traffic jam – a heart attack.
Statins reduce the circulation of the LDL taxis. In certain cases, more often than not, the trash-carrying trucks may also go on strike. The problem is compounded by the proliferation of an independent taxi enterprise – the TG and the VLDL. These circulation problems have a name: dyslipidemia.
Under these circumstances, the accumulation of cholesterol in the arteries goes on, while we’re under the impression the problem has been solved. That’s why doctors talk about residual risk, and that’s why they want to associate other drugs to statin to act against these disturbing elements. Thus, the task at hand is to lower the number of independent taxis (the TG and VLDL) and increase the number of trash-carrying trucks (HDL). It’s much more complicated than it sounds.
Professor Jean Davignon, of the University of Montreal, says the world is “facing a paradigm shift. This is the end of the statin era. We have to look beyond LDL [bad cholesterol]. The broader we are, the better. We must consider all aspects of atherosclerosis”. (Aatherosclerosis, as mentioned, is the accumulation of cholesterol fat in the arteries.) It was Davignon himself who coined the fabulous term “cholesterocentric world” – the world we all live in. Now he asks, “But what about other risk factors” causing heart diseases?
Studies show that even with statin treatment, “major coronary events” still happen at a staggering rate of 77%. Moreover, statin and other intensive therapies still cannot prevent the progression of what is called microvascular diseases (which include eye diseases, renal failure and amputation) in up to 50% of patients that already suffer from diabetes. Diabetes and obesity can become evil twins, and are commonly described in the medical industry as “diabesity”.
R3i to the rescue
That’s where R3i steps in. Its “mission” is to improve the lives of people suffering from heart disease and/or diabetes. The initiative is adamant: “The residual vascular risk issue has become a major public health challenge in all geographical regions.”
This is not philanthropy, of course: the project is run by a Swiss-based foundation, with initial seed funding by Belgian-based Solvay Pharmaceuticals, and led by a board of trustees and an international steering committee of 21 specialists in cardiology, diabetology, lipidology, endocrinology, epidemiology, nutrition, ophthalmology, nephrology and basic science. The foundation is now actively negotiating supplemental grants with other Big Pharma players and the food industry.
According to the American Journal of Cardiology, R3i is committed to research, educational programs and making sure that the core issue – technically described as “residual vascular risk associated with atherogenic dyslipidemia” – becomes a global priority. More than 40 countries are already involved in research and educational programs. Professor Sy of the University of Philippines defines R3i as “a neutral group. What we need to do most of all is to alert primary physicians”.
The ghost of “diabesity” is now haunting Asia. From 2000 to 2025, diabetes in Asia will increase by 85%. According to an alarming, recent study conducted in 3960 individuals aged 20-74 from urban and rural areas of Fujian, China, 29% were overweight (including 3.5% that were obese). Around 10% suffered from diabetes. And 14.5% had a condition called “impaired glucose tolerance”. In a 2002 report on hypertension in China, 24% of individuals were affected, 78% were treating it, but only 19% had it under control.
According to the International Diabetes Federation, in 1985 there were 35 million people with diabetes worldwide; in 2000, they were already 150 million. By 2007, they were more than 110 million in Asia alone. By 2025, they will be a staggering 380 million. In Southeast Asia alone, diabetes among 20 to 79-year-olds, in 2007, affected 46.5 million people. By 2025, it will affect 80.3 million people.
India has the highest number of people with diabetes in the world: 40.9 million. By 2025, also according to the International Diabetes Federation, that number will be 69.9 million. Not to mention an extra 35 million with impaired glucose tolerance.
On a global level, the rate of obesity and overweight children has increased from 0.2% in 1970 to 2% in 2007. This means a staggering 400,000 new cases of obese children every year. It’s important to remember that obesity can lead to diabetes.
The Chinese authorities won’t fail to notice that the economic burden of diabetes now represents around 17.6 billion yuan (roughly $2.4 billion) a year, and growing.
Welcome to the Lipid war
It goes without saying that R3i is an inevitable by-product of globalization. The directors of the initiative are the first to point out that the road to less residual vascular risk implies weight loss, a healthy diet, frequent exercise and no smoking – even in the case of people already being treated with statin.
But try convincing Asian masses especially in India and China they must abdicate from their Big Mac and fries. Or stop smoking – be it kretek cigarettes in Indonesia, bidis in India or non-filter torpedoes in China. If people won’t change, or the appeal of the fast food industry and the tobacco industry is too powerful, the answer has to come from educating the public plus, inevitably, pharmacotherapy.
R3i recommendations are fundamentally sound. They involve above all a change in lifestyle; normalization of blood pressure; and, as physicians stress, “earlier intervention in the natural history of the disease”.
Residual vascular risk is so crucial because research for the past 20 years has identified obesity, dyslipidemia, high blood pressure and raised blood sugar as the key risk factors associated with cardiovascular disease and diabetes. Dyslipidemia alone is a major culprit: 54% as far as the risk of heart attack is concerned.
Microvascular complications, per se, do not kill. But their effects can be simply devastating. For instance, diabetic eye disease is the number one cause of blindness in working-age adults. Diabetic nephropathy is the number one cause of end-stage renal failure. And diabetic neuropathy may lead to amputation of the lower limbs.
For Big Pharma, the so-called Lipid Lowering Agent (LLA) market – the whole business of drugs that lower cholesterol – used to be a booming market ($26 billion in sales in 2008). Now this “gold rush” is over; welcome to the age of generics (mostly made in India).
The fact that the market will inevitably continue to grow in volume also means that the price of the available drugs keeps falling, squeezed by the increased availability of generic drugs. A branded LLA pill costs $3 to $4 a day for the rest of your life. A generic equivalent costs $0.7 to $1.9 a day. The social function of the spread of generics is essential – as they benefit more and more patients.
According to industry data, the LLA market in China in 2008, for instance, was worth almost 1.4 billion yuan (almost US$190 million), with 35 million pills sold. It has been in steady progress since 2004. This reflects a relentless, worldwide growing trend in emerging markets – the new frontier for Big Pharma.
New drugs are expected to be in the market within the next few years. But what kind of drugs? Professor Sy of the Philippines puts it as “a poli-pill. Or various poli-pills, especially helpful for low to middle-income countries. Single pills that take care of blood pressure, blood sugar, diabetes, will be helpful. But to tackle severe hypertension, several classes of drugs are needed”.
Yet there’s more to it. Once again, why is residual risk so important? Because as mentioned before, people treated with statin are still dying of cardiovascular diseases. Residual risk opens the way to the making of “poli-pills” – in this case, single pills that will tackle all aspects of cholesterol. This means the industry going the crucial step beyond statin. Once again, it’s high-stakes poker – a new source of huge profits for Big Pharma, on something that concerns us all, and not only stock market players.
And once again the perverse effects of Asia copying the Western globalization model come full circle. The global fast food industry turns people’s eating habits upside down and Big Pharma steps in with a cure. Everyone profits. But not necessarily those in the wake of their strokes and heart attacks.