Union health minsitry has banned the controversial anti-diabetic drug Rosiglitazone(marketed by GlaxoSmithKline as Avandia,and variant brand names produced by different pharma companies like Reddys, Sun, Glenmark etc.), based
on an expert committe recommendation. This recommendation is driven by the reasoning that the continued use of drug ups the chances of heart diseases and is particularly dangerous to Indians, due to their perceivced higher genetic pre-disposition to heart ailments. Given the prevelance of diabtes in India, this is a serious issue of public health concern.
I had sent out the question to a couple of experts on this field and gotten the response.The response from Dr. Anoop Misra here. Dr. Anoop is the head of diabetology at Fortis and was in the limelight on this issue.
1. Could you just take us through an overview of this recent news announcement of Avandia drug ban, focussing on what this drug is meant for, how widespread is its usage in India, what are the implications of this ban?
When introduced in 1999, this drug was believed to be excellent drug for diabetes since it was acting not only on blood sugar but also on liver and fat showing multiple benefits. Since then it has been regularly used as frontline therapy in diabetes. Till 2008, it had nearly 25% of share of all diabetes drugs in India, but since then the used has been declining due to reports of adverse reactions
2. Could you just give us a perspective on the evolution of drug development for diabetes and position the role of Rosiglitazone in this? Also, are there guidelines/framework to the industry on the development of drugs for diabetes and if yes, did the Rosiglitazone conform to all those guidelines?
By 2002, Thiazolidinediones (Troglitazone, Rosiglitazone and Pioglitazone) were at the center point in the treatment of diabetes. These drugs were developed according to strict drug development guidelines of FDA. However, at this time, FDA was not evaluating toxicity, if any, of any drug given on chronic basis, on heart.
3. Could you just give us a overview of the process that a new drug discovery needs to get through before it is approved to be marketed and is this process guaranteed to protect the interest of the patients? Does this process itself has inherent limitations and if so, how does it adress those?(It would help if you provide this explanation taking the example of Avandia itself)
Drug development process is long and tedious but not without shortcomings. After animal studies, phase 1, 2 and 3 studies are performed in limited number of human subjects to evaluate safety and efficacy. Most of these studies are of 3 months to at the most 2 year duration. These studies do not ensure that investigational drug does not cause side effect in larger number of patients after it is clinically used, since a particular side effects was not noticed in limited number of subjects. Further none of the studies could tell us what would be long term side effects of the drugs e.g. after its use for 5-10 years. The heart side effects of Avandia were not properly noticed till large number of studies were collectively analysed five years after it was first introduced.
4. Specific to this Avandia, it has been in the past removed from the market(US, through FDA ban) because of its unacceptable high risk of liver failure and later study found it to be safe? So does this mean that there could be a repeat phenomenon like this with the current ban too?
Any ban of any drug cannot be lifted. Please note that it was sister drug Troglitazone which was banned because of liver side effects and not Avandia.
5. Does the public confidence on regulatory bodies in protecting the patients interest and on the treating physicians on their choice of drugs get affected due to these kind of stories and what could be done to adress that?
Any drug regulatory body is not without its faults and bias. US FDA has clearly dragged its feet on Avandia, and strict action should have been taken long back. DCGI office (India) has much improved after current DCGI has taken over, however needs to be given much more support from Government with more powers.
6. Are there precedences in India, for such a ban on any chronic medicines? How did the post ban scenario span out in those cases, and could there be any learnings from that for this ban? Given the perceived high genetic pre-disposition to heart ailments do you think India has acted at the right time or they could have been more pro-active(Given the fact that Europe has done this ban couple of months ago and US has given restricted use recommendation a while ago)?
Please note that regulatory action from US FDA (strictly restricted use) and by European agency (Ban) has come only on 23rd September, 2010 not before that. Only black box warning was put on Avandia before this by USFDA. Considering this, India has clearly acted in proactive manner. Even before this, India was first country to ban ongoing trial of Avandia. Previously, Indian regulatory authority (DCGI) had reacted swiftly in similar manner for banning weight loss pill Rimonabant.
7. Now coming to the implications of this ban, What do patients who are currently on this drug do?, Suppose for a doctor who has prescribed this medicine to a patient for a long period of time and has clinical evidence to demonstrate the suitability towards this against other approaches (Intolerance to metformin kind of scenarios)(I know a "popular" diabetologist has explicitly stated that he has adviced a patient who is on this drug to continue and suggest that nothing will happen to his heart, though this interview was before the ban announcement) do in such a case? Are there suitable alternatives to this that poses less risk as against Rosiglitazone?
I cannot comment on other people’s practices, but our team had stopped using Avandia 2 years back, and I had emphatically lectured to various general practitioners and discussed with all prominent diabetologists in India to do so. We were never in doubt that this drug is not good for heart. Presently, there are a number of alternative drugs are available and any physician should be able to smoothly change from this drug to another without any loss of control. Even its sister drug, Pioglitazone could be used on its behalf since based on current data, it is safe.