Cocktail Drugs

Written by BV Mahalakshmi | Sudhir Chowdhary | Updated: Jul 22 2008, 02:42am hrs
Medical researchers are moving closer to affordable, multiple-target, fixed combination polypills for prevention and cure of cardiovascular disease, HIV, malaria and tuberculosis (TB).

The first to hit the retail chemist stores in the next two years would be five-in-one drugs for treatment and prevention of heart attacks and stroke. Such drugs will offer millions of heart patients the convenience to strictly comply to their medications by simply popping a single pillcontaining medications for dilating arteries, relaxing heart muscles, removing excess water and salts, preventing clot formation, and reducing bad cholesterolthereby getting rid of the boring yet essential exercise of swallowing four to five tablets a day.

Drug maker Cipla seems to have an early mover advantage. Says Amar Lulla, joint managing director, Cipla, We have made a headstart by launching two-in-one and four-in-one combination drugs for heart ailments. Currently, we are working on more combo pills for people affected by heart attacks. Besides, clinical trials are progressing for a five-in-one pill.

Dr Reddys Laboratories (DRL) is another player in the arena and claims to have completed trials for its four-in-one polypill. Analysts inform that several varieties are being developed around the world for different types of cardiovascular disease. Some of the institutes are Spanish National Centre for Cardiovascular Research (CNIC), and the Ferrer laboratory in Spain. Among big pharmaceutical majors, Pfizer, AstraZeneca, GSK and Aventis are some of the companies that have shown interest towards polypill development.

These may have a small market share, to begin with$750 million at launch time in 2010 out of the $11-billion pharmaceutical market for cardiovascular segment. The calculation rests on the assumption of sales of products sold in single dosage format as opposed to the fixed dosage combos, reflected by polypill constituents.

However, excitement in the market seems to indicate a steep growth curve. We have completed trials for our four-in-one polypills in India and the data is under compilation. We expect to make an application to the Drugs Controller General of India (DCGI) soon. Now, the global clinical effort is on and regulatory approvals have been received for pilot trials from USFDA, MHRA, TGA (Australia), Medsafe (NZ) and DCGI (India). Besides, we have a partnership with University of Auckland for the trials, says Raghu Cidambi, advisor, Dr Reddys Laboratories. Clinical trials would involve 600 people from five continents. They would be drawn from New Zealand, India, Australia, Brazil, China, South Africa, the US and the UK.

Local clinical trials for DRLs polypill were completed in July last year across 11 centres in the country. The evidence from the clinical data is very strong. It is not an irrational combination and we have got solid clinical evidence with our data,

says Cidambi.

Our offering is unique as it does not fall under any blockbuster category nor traditional drugs; but a new molecule, which would be made available to the needy at an affordable price, he insists.

The cost of a monthly course (30 tablets) of DRLs polypill will work out to only Rs100, compared to the prevailing cost of Rs 400-500 for multiple tablets, travails included. Isnt it surprising But, this is the promise these wonder drugs hold for patients and doctors alike.

The significance of this breakthrough is multi-pronged. Firstly, the medical fraternity is finally working on prevention of diseases plaguing mankind, instead of the earlier practice of focusing on its treatment. Secondly, the polypill approach is being directed not only towards those at the risk of heart problems and stroke, but also towards the treatment and prevention of equally devastating illnesses like tuberculosis (TB), malaria and HIV. It is believed that several domestic drug companies have intensified their research efforts in their endeavour to develop combination drugs. Those closer to the market include one that brings together two asthma medications and another that combines three HIV drugs. Thirdly, the polypill approach is opening another vista to the Indian drug companies to tap the global markets. Their research efforts are getting strengthened in their ability to develop affordable combination drugs that focus on the treatment of various diseases as well as their prevention.

Current treatment usually involves treating one cardiovascular problem with at least two drugs. Future treatment would involve treating a group of cardiovascular problems with one pill containing multiple drugs.

Since Indians are at a high risk of contracting cardiovascular diseases, development of such a polypill, which combines multiple drugs proven to be of benefit for heart diseases, makes sense, says Anoop Misra, director and head, department of diabetes and metabolic diseases, Fortis Hospitals (New Delhi and Noida).

Every year, over 17.5 million people die due to heart diseases all over the world. India has the dubious distinction of having the largest shareover 2.8 million.

Misra, however, insists there are several issues to be considered. If given on a mass scale, are these polypills cost-effective It is likely that some people will develop side effects. Would these have advantages over strict diet and exercise Should we give it to all people, say those above 50 years Why should a non-obese person with normal blood cholesterol, no family history of heart disease, taking balanced diet and doing regular exercise, take such a pill for several decades till he dies His argument in a nutshellTo give it to the population and considering the costs involved, data from large scale trials are needed.

Without any doubt,

practical issues that have to be addressed with the polypills will include clinical trials, the commercial incentivepolypills will be a high-volume, low-margin productregulatory approvals, and clinician and patient acceptance. There are several varieties of polypills under development around the world for primary and secondary prevention of cardiovascular diseases, informs Misra.

Irrespective of who launches first, the good news is that those who are working on the product have low- and middle-income countries very much on their radar, and are trying to ensure that the products are affordable and widely adopted in those parts of the world where they can have the greatest impact.

Tracing its genesis, two British researchers, NJ Wald and MR Law, were the first to put forward the idea of a polypilla combination of three or more drugs in a single pill for the prevention of cardiovascular disease. Based on theoretical considerations, they projected that such a pharmaceutical product should enable the worlds healthcare systems to decrease the incidence of heart diseases by more than 80%.

Although the initial publication was met with a degree of skepticism, it appears that the concept was premature at that time.

Over the next 10 years, many different versions of the polypill will become available, say analysts.

With research and clinical trials in full swing on innovative and varied polypill formulations, combination therapies hold significant potential to fill the requirement for simpler and less expensive treatment regimens.

Though the current focus is on the treatment of cardiovascular disease, the polypill approach is also being directed towards HIV, malaria and tuberculosis. Sustaining the success of this therapy would require the manufacturer to overcome potential hurdles of efficacy, safety and cost-effectiveness with robust clinical evidence, says Sandhya Kamath, senior research analyst (healthcare), Frost & Sullivan.

DRLs polypill will give 60% risk reduction either for occurrence or delay or prevention of a heart attack or stroke. Patients with a known history of heart disease and also those who have had a stroke can simply take just one pill, instead of popping all the four, states Cidambi.

Meanwhile, hectic efforts by drug companies to push polypills into the national health programmes to reach the masses does not seem to be cutting ice with the government.

There is very little effort by the government agencies to use polypills as part of the public-health system, says a senior scientist at a leading drug company. All the four ingredients going into the pill are recommended therapy for people who had an heart attack or a stroke, says Cidambi, adding, these are approved safe drugs in use that have been already proven for safety and efficacy.

It is seen that research undertaken now focused predominantly on the use of a polypill for secondary prevention after a heart attack.

Going forward, future research will most likely target use for primary prevention in populations where individuals are at high risk because of increasingly urbanised lifestyles and greater age, but are currently without overt health problems.

As per World Health Organisation (WHO) estimates, India will have 60% of the worlds heart patients by 2010, fuelled by risky lifestyleswhich include junk food, lack of exercise and smoking. This could spell a huge opportunity for polypills in the country.