cancer, medicine, Science, Science and society, Society

Cheap drugs for all?

After my somewhat depressing previous post, I decided to comment on something a little more optimistic this time around, namely the success in getting treatments for some of world’s most underfunded diseases afflicting the world’s poorest people. And at a knockdown price, too…

It’s long been known that the big funding for medical research goes into diseases that predominantly affect the developed world, namely cancer and cardiovascular disease. These countries effectively wiped out most of their deadly infectious diseases a long time ago, through vaccination, antibiotics and vast improvements in living standards. Now, money tends to pour into non-infectious diseases that are have complex causes and generally kill later in life (primarily cancer and heart disease). Meanwhile, diseases that kill millions each year in poorer countries get a fraction of the funding. The WHO estimates that a group of 18 priority “Neglected Tropical Diseases” afflict over a billion people in nearly 150 countries. And that’s before you even factor in malaria. Incidentally, a lot of the diseases on this list are parasitic infections: for various reasons, which largely boil down to (a) complicated life cycles and (b) being eukaryotic cells, i.e. the same type as us, these are notoriously hard either to treat or design vaccines for. Nevertheless, “neglected” can seem a bit of an understatement. There’s a detailed analysis here [1], from which the following graph was taken:

doi:10.3402/gha.v8.25818

The trouble is: drugs cost money, right? Lots of money. The Tufts Center for the Study of Drug Development in Boston estimates that the average cost of developing a new drug from scratch and bringing it to market is a whopping $2.5 billion. The pharmaceutical industry may make a profit out of pricey drugs targeted at conditions that primarily affect well-off Western populations, but they argue that they have to recoup their investment. Well, yes…but there’s a few buts there.

Even the chief executive of London-based pharmaceutical giant GlaxoSmithKline, Andrew Witty, has called billion-dollar estimates “one of the great myths of the industry” [2]

For one thing, there’s a huge amount spent on business stuff, not science stuff, like marketing research and advertising. For another, I have a bit of a bugbear with pharmaceutical companies moaning about how R&D is so expensive when a lot of their work spins off from basic research done in publicly funded universities (that then get no profit back; nor does the taxpayer). People in the industry reckon that too much investment is put into drugs that offer only marginal improvements over existing ones, often to corner the market from a competitor.

This market-driven model of funding results in all sorts of oddities, in addition to these gross injustices. Take cancer: breast cancer and prostate cancer kill similar numbers of people per year in the UK. The proportions of cancer funding don’t correlate with the number of deaths. There are complexities here to do with demographics: cancers that hit younger people harder tend to be more aggressively funded: brutal as it sounds, breast cancer frequently kills young women, often with young families; prostate cancer almost exclusively kills old men, and cancer is primarily a disease of old age. However, it’s also the case that good quality research into one type of cancer attracts more funding, which results in more better quality research…etc. This leaves some cancers as “neglected” because they’re difficult: pancreatic cancer isn’t far behind the number of deaths compared with prostate and breast, but gets a fraction of the funding. (I should also note that cancer is a huge killer in the developing world too, effectively making it “neglected” there too – but this is heavily down to lack of access to existing high-quality screening and treatments).

cancer-funding

Lest you think that this is one area in which women benefit over men, think again: vast amounts of money are spent on drugs for erectile dysfunction, which, whilst distressing to millions is not going to kill you, and yet money for endometriosis, an agonising and debilitating condition which affects about 1 in 10 women, and can cause infertility, gets a pittance.

Oh, and almost no one is funding research into new antibiotics, which we really really need, because, right now, it’s not going to make a profit, something that makes scientists throw their hands up in despair (but probably not as much as refusing to ban antibiotics as growth promoters in farming….)

Médecins Sans Frontières (Doctors Without Borders) launched its own initiative to tackle these funding problems a little while ago: The Drugs for Neglected Diseases Initiative. In just over ten years, this initiative has got approval for six treatments for a variety of tropical diseases, and has 26 drugs in development – and for less than $300 million. How? As noted in this Nature News feature:

The model for its success is the product development partnership (PDP), a style of non-profit organization that became popular in the early 2000s. PDPs keep costs down through collaboration — with universities, governments and the pharmaceutical industry. And because the diseases they target typically affect the world’s poorest people, and so are neglected by for-profit companies, the DNDi and groups like it face little competitive pressure. They also have lower hurdles to prove that their drugs vastly improve lives [2]

That “little competitive pressure” comment is a critical one. A lot of drugs never make it through to actual treatments, or even all the way through clinical trials, not necessarily because they’re ineffective, but because they’re just not profitable. Pharmaceutical companies are businesses, and if they don’t make a profit, they rapidly become bust businesses. How does DNDi do it?

Drug development from scratch is arduous and expensive. It begins with experiments on hundreds of thousands of chemicals in the lab, looking for one that kills a pathogen without harming the host. The DNDi does not have a laboratory, so it does this through collaborations. It searches for promising leads in compound libraries generated by biotechnology and pharmaceutical companies. Many firms are willing to share access to these precious libraries because the diseases that the DNDi targets will not result in blockbuster drugs, so it is not infringing on their turf [2]

So they’re taking the future drugs the pharmaceutical companies have thrown by the wayside as non-profitable, which is all to the good, and using their libraries of chemicals to search for things they are interested in but the companies are not. Moreover, being non-profit, and relying on networks of collaborators offering work for free or at reduced rates, massively reduces the costs.

Now, as results of clinical trials are nearing their end, it looks like DNDi has had a big success in finding a drug that treats sleeping sickness, fexinidazole, with another in the pipeline.

discount-drugs

Moreover, new results have found a potential drug that will treat not one but three major neglected tropical diseases: Chagas Disease, leishmaniasis and sleeping sickness, which infect 20 million people and cause at least 50,000 deaths a year. These are all caused by a type of organism called a kinetoplastid parasite: they share a similar biology, and the drug targets the protein recycling machinery [3] of their cell.

It’s interesting to note that, whilst human trials in regions where these diseases are endemic are incredibly difficult from a logistics point of view, from a medical point of view existing treatments are so poor and out of date that any improvement can make a huge difference and be easily detectable. In a sense, there’s a lot of low-hanging fruit ripe for picking because there just hasn’t been the concentrated research effort into finding drugs for these diseases. Contrast this with the drugs the big companies focus on developing in the developed world: often they are looking for ones that are highly similar to those that already exist, and offer only an incremental improvement on the current treatment. Why? Because current drugs go out of patent, and because if they can market their very-slightly-better drug they can oust a competitor’s drug.

What next? Well, apart from developing a better way to develop drugs than capitalism, that is. DFNDi is aiming to search for new antibiotics to treat resistant infections in the developing world. Perhaps the richer countries of the world will be buying them back one day in the not too distant future….

References

[1] von Philipsborn et al, 2015: “Poverty-related and neglected diseases – an economic and epidemiological analysis of poverty relatedness and neglect in research and development.” Glob Health Action 8: 25818 http://dx.doi.org/10.3402/gha.v8.25818

[2] Maxman, 2016: “Busting the billion-dollar myth: how to slash the cost of drug development”. Nature News, vol 526, issue 7617.

[3] Khare et al, 2016: “Proteasome inhibition for treatment of leishmaniasis, Chagas disease and sleeping sickness”. Nature 537, 229–233. doi:10.1038/nature19339

 

 

 

 

 

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