Interview with Pharmaceutical Coordinator Elodie Jambert
3 March 2010
Over the last nine years, Untangling The Web
http://utw.msfaccess.org/background/aids_progress_under_siege (읽어 보시기를 추천합니다!)
has provided an annual snapshot of what’s happening to the costs, availability, adaptability and patent issues surrounding antiretroviral medicines for AIDS treatment in developing countries.
This year, new WHO guidelines on antiretroviral use, falling second-line drug prices and the continuing neglect of paediatric medicines are among the trends picked out by our pharmaceutical team.
In late 2009 the World Health Organization brought out new guidelines calling on governments and other treatment providers to phase out the use of the antiretroviral stavudine (d4T) and start using improved drugs. Why? And how will the switch affect the price of treatment?
In fact WHO has been trying to steer patients away from using d4T in their antiretroviral combination therapy for a few years now. d4T is a drug which has been a cornerstone for treatment for millions in the developing world and has allowed us to scale-up treatment considerably, but it has significant toxic side effects.(lactic acidosis, lipodystrophy, etc) These side effects can sometimes be so severe that patients find they can’t stick to their treatment. If you interrupt treatment not only does your health suffer but you are also more likely to develop resistance to drugs.
But countries have been reluctant to make the switch in treatment programmes because of the higher price of the improved replacement drugs, such as tenofovir (TDF) and zidovudine (AZT). So there has been a financial barrier in the way of improving patients’ regimens.
But now, over the last few years, as a result of competition between generic manufacturers, we have seen the price of tenofovir drop considerably. In the last year alone the cost fell by over one third. This means that today, the improved three-in-one combination pill with TDF (TDF/3TC/EFV) – recommended by WHO – costs US$176 per patient per year (ppy) from generic sources.
That price is still higher than for the ‘older’ first-line regimen with d4T. The most affordable versions of these today cost just $68 ppy. But it is still a considerable saving on earlier prices. And as more countries and treatment programmes make the switch to TDF or AZT, there will be more demand which will push the price down yet further.
What about people who have been on antiretrovirals for a while now but whose drugs are becoming ineffective as patients grow resistant to their medications – how much does second-line treatment cost today?
The good news is that while the most affordable second-line treatment is indeed still more expensive than the improved first-line combination, the cost gap between the recommended first- and second-line treatment is going in the right direction and narrowing. Last year, the most affordable second-line treatment was well over eight times the cost of the recommended first-line treatment. This year, the most affordable second-line is expected to be made available later at $425 ppy. That will be just under two and a half times more expensive than an improved first-line regimen.
One of the main reasons for this success is that one of the drugs most commonly used, the protease inhibitor, lopinavir/ritonavir (Kaletra or Aluvia patented by Abbott) recorded a dramatic price drop. The price of the generic version has now fallen by over half in the last three years alone to $475 for a year’s treatment for each patient.
At a glance: How much does it cost to…
Treat a child with HIV/AIDS who has just started on treatment (first line) antiretrovirals for a year: US$61
Treat an adult with the improved WHO recommended first line treatment for a year: US$176
Treat an adult who has developed resistance to their original treatment with second line drugs for a year: US$425
Treat an adult on third-line treatment for a year : More than US$2291
It’s important to note that while the figures quoted are the lowest available, they may not be applicable in all developing countries – in some places because of patent barriers, the prices are considerably higher. Prices accurate as of March 2010.
In another first, the new WHO guidelines also call for the provision of a third-line drug regimen for those patients who have grown resistant to earlier therapies. To what extent are these drugs available to patients in developing countries and at what cost?
Several new drugs have come through development recently that work in radically different new ways to stop the HIV virus replicating. Some of these drugs are already used by patients in rich countries. They are, as you might expect, very expensive.
Many of the pharmaceutical studies are still ongoing but at this stage it looks likely that the drugs that might be included in any proposed third-line regimen in developing countries would include darunavir, etravirine and raltegravir.
To give you some idea of the costs involved, raltegravir is offered by the originator company in low-income countries at a price of $1113 for one year’s treatment. And this is the price for only one drug in a combination of three different drugs, so we calculate that the cost of a third-line regimen would exceed $2291 ppy. This is totally unaffordable for patients or governments in developing countries.
So although it’s good that the WHO recommendations highlight the need for third-line therapies, as we will definitely need these in the not so distant future, we’re still lacking a mechanism that makes sure these can be priced within reach of patients and caregivers like MSF.
But if the prices for the ‘older’ first-line were brought down from $10 000 to just $68 today, then why can’t generic versions help to make these newer drugs for which there is a growing need more affordable?
The problem is that these very new drugs are often already patented in the countries which traditionally have the capacity to produce generic drugs. So for instance, India, which is the main producer of generic medicines for the developing world, now grants patents on newer medicines – this was not the case before 2005. And some of the newer drugs outlined in the 2009 WHO guidelines such as raltegravir, etravirine and maraviroc for example, are all already patented in India, blocking out the possibility of generic production and competition.
Some originator companies do offer different prices for different developing countries for their products– how much of an impact does that make in the case of the drugs we are discussing?
Many companies do indeed operate these kind of differential tiered pricing systems, arguing that this is a good way to ensure access to medicines by pricing them at levels people can afford. But this just isn’t true. Let’s take tenofovir as an example. What’s critical is that some countries are excluded from this deal – patients in some middle-income countries are expected to pay an enormous $1033 for the originator product. The vast majority of patients in middle-income countries live in poverty and will not be able to afford life-saving medicines at such prices.
So what can be done?
Although we have seen that the cost of certain medicines has come down significantly because of competition among generic manufacturers and increased demand, overall prices for newer drugs – by which I mean both those that already exist and those still in the later stages of development - remain unaffordable for developing countries and out of reach of national treatment programmes.
We need to face these challenges in a number of different ways:
Firstly, we need to ensure is that patents are not granted frivolously, on medicines that are not genuinely new. And also that when patents have already been granted on medicines, but inappropriately, that these patents are challenged. In India, civil society groups are pursuing this strategy through a series of pre- and post-grant oppositions to drug patents.
Secondly, it is essential that countries make use of the flexibilities in international trade law and implement compulsory licences when they need to get hold of necessary medicines at affordable prices.
Thirdly, we need to support new ideas such as UNITAID’s patent pool. This innovative mechanism would allow drug companies to pool their HIV drug patents in a pool in return for a licence fee, opening the way for generic drug companies and others to produce more affordable versions for developing countries.
Treatment for children has always lagged behind treatment for adults in developing countries – have there been any positive developments this year?
The cost now of treating a child with first-line antiretrovirals is $61 per year, which is actually slightly lower than the price for a current adult treatment.
But the main concerns with paediatric treatment don’t lie with the price alone. We have been beating the drum for improved paediatric treatment for some time but still, of the 22 antiretrovirals approved by the U.S. Food and Drug Administration, six are not approved for use in children and seven do not come in any kind of paediatric formulation. We need to expand the treatment options open to children with HIV.
As an example of the need for improvement, we urgently want to see right now the development of a more adapted heat-stable formulation – either as dissolvable granules or sprinkles - of the boosted protease inhibitor, lopinavir/ritonavir, for younger children who cannot swallow the current pills which are simply too big and can’t be crushed by caregivers either.
But the bottom line is that if prevention of mother-to-child transmission programmes were implemented more successfully in developing countries, as they are in Europe and the United States, we wouldn’t still be seeing the alarming infection rate among children anymore. There is an urgent need to address this.
