Diseases like malaria, dengue and ebola entrench poverty, taking away as many as 56 years of healthy life from people who suffer from them. Yet there are emerging changes in international patent law. Do generic drugs still stand a chance of making a big impact on these diseases, as they have in the past?
India supplies 92% of the AIDS drug in current use in developing countries, and was even referred to as the “pharmacy of the developing world” by South African Health Minister, Aaron Motsoaledi. In 2011, India provided 17.7 % of all pharmaceutical imports to the entire African continent. Of the more than 60,000 HIV/AIDS patients in nearly 30 countries in Médecins Sans Frontières’ projects, 84% receive generic medicines made in India. The industry also supplies other generic drugs at affordable prices to impoverished countries worldwide, particularly in Latin America and Asia. In the 1970s, India’s patent laws were relaxed and drug producers could reverse-engineer and supply the world with cheaper versions of patent-protected, or originator drugs. Generic drugs proceeded to proliferate the developing world, putting the odds back in their favour, especially against AIDS, tuberculosis and parasites.After the expiry of the patent, generic pharmaceuticals can be produced and sold by anyone. These are also subject to regulation by the same authorities as the brand name drugs. According to FDA regulations, these generic drugs are identical to their originators.
In January 2005, India conformed to the World Trade Organisation’s Trade-Related Aspects of Intellectual Property Rights (TRIPs) agreement, restricting manufacturing and marketing of generic drugs patented by foreign pharmaceutics companies to only situations classified as a major public health need. It does so under a clause called ‘compulsory licensing’, that gives India and other countries with a high disease burden some leeway to treat its own people. Drug manufacturers still had to maintain profits somehow, so the surplus in generic drug supply was redirected to the United States and Western Europe, to replace sales lost to TRIPs compliance.
Indian drug manufacturers began entering research and development agreements, mergers and acquisitions with these foreign pharmaceutics firms and the link between them grew as Indian drug companies realised the profitability of Western markets compared to that of developing countries. However, since seizures of shipments of generic drugs by EU, under the premise that these drugs were not legally produced, India has been in talks with the EU and under pressure from the US to undertake more intellectual property barriers, particularly ‘data exclusivity’. This would mean that generic drugs can no longer be registered based on existing data about their safety or efficiency. Generic drug manufacturers will either have to wait five to ten years before the patent runs out on the expensive, original drug or run their own, unnecessary clinical trials. Generic drug manufacturers seem to see this process of ‘evergreening’ as a threat to their business model. However, India’s Prime Minister, Narendra Modi seems keen on these reforms, responding to concerns about the supply of generic drugs to developing countries with assurances that they will “protect the Indian pharmaceutical company”. In essence, the shift in focus to the profitability of generic drugs in the developed world seems to be guiding Indian diplomats in their negotiations.
Innovation or affordability?
The incentive to innovate needs to be balanced with affordable healthcare for the developing world. Generic drug production allows us to supply the developing world with the drugs they need to relieve their disease burden. Drug manufacturers in India can circumvent research and development costs. To get a drug approved, companies need to register a patent and only then can they run clinical trials that determine whether the drug is safe and effective. Biogen Inc. will need to invest US$2.5 billion (£1,753,525) in its experimental Alzheimer’s treatment before knowing whether it’s even effective. The figure includes the costs of running trials and building a manufacturing plant for the drug. Biogen has to take the risk of building before trial results because it takes four years to get a manufacturing plant set up. At the same time it has to stand as formidable competition against Eli Lilly, the company that stands at the forefront of treatment for the disease. As of July 2015, shares of Eli Lilly have risen more than 30% over the past year, fuelled, in part, by optimism over their newest drug – Solanezumab’s ability to drastically reduce Alzheimer’s progress in early-stage sufferers.
Thus, there are legitimate concerns of drug companies that they would not be able to attract top talent, innovate or cover their costs if they are not able to profit from the sales of their drugs. Generic drugs reduce the incentive to innovate because generic drug manufacturers can skip ahead to the profit-making stage. Yet, when funding for global health programs is dwindling, evidenced in current global health budgets, these affordable drugs are more important now than ever. In countries where health care systems and institutions are weak, or insufficient, non-governmental organizations (NGOs) often step in to fill the gap. The Bill and Melinda Gates Foundation alone has committed US$2.5 billion in HIV grants to organizations around the world, and US$1.4 billion to the Global Fund. Their Avahan program in India has been able to prevent more than 100,000 new HIV infections.
Cheaper by the dozen
In India, there are government-supported Jan-Aushadhi stores which sell drugs at their production price. Comparing the prices at these stores and in other privately owned pharmacies, the price difference was 15.5% for quinine (widely available generic chemical) and 230% for Artheether (originator drug). This gets compounded by the fact that if a patient becomes resistant for one line of drugs, they need to be put on the second line of treatment. However, quinine has several drawbacks, including a short half-life, painful local reactions after intramuscular and intravenous administration and neurotoxicity. Permanent blindness with standard doses of quinine has also been well documented. Resistance to quinine is widespread, and thus it is less effective, while Artheether is used as the second line of treatment or for more severe cases. The price difference between the two means Artheether is unaffordable for many people in developing countries. In India, healthcare costs are paid mostly from the patients’ pockets. Unskilled workers pay as much as two to three days’ wages for the treatment. If someone develops resistance to the second line of treatment, there are few affordable options left, since the newest drugs are often still under patent for the better part of a decade.
As in India, generic drug companies across developing countries have the potential to innovate and improve healthcare outcomes for their people. As an example, drugs for ebola, HIV/AIDS, malaria and tuberculosis sometimes need to be refrigerated. Many patients in the may not have a refrigerator, and in some more remote places, they may not have power supply. Formulations designed for the developing world, such as drugs or vaccinations stabilized for warmer temperatures in silk, are more likely to be developed by generic manufacturers in developing countries than originator companies based in Western countries.
Generic drug companies are better placed to adapt these formulations for developing countries, because of a profit-incentive to exploit large consumer markets. For example, fixed-dose combination pills are an innovation of the generic drug industry. Their offers resemble holiday package deals in which one can book a hotel, flight and activities separately, or as a package, tailored to your needs. Likewise, they can combine two or three pills in one, making practical assumptions about the treatment regimens for diseases requiring complex care. This simplifies treatment by allowing a patient to take one pill, once a day rather than a few to be taken at various times. This has enormous implications for adherence to treatment schedules, especially for the working class in developed countries who may take long hours and cannot afford to take as many breaks. Fixed-dose combination pills are not manufactured in Western countries, precisely because of the patent barriers that exist. Drug companies in developed countries prefer to design them for their own populations’ needs to maintain profitability.
What’s the cure?
For the same reason originator companies choose not to design drugs that can withstand developing world conditions, they choose not to create formulations for developing world diseases, because they would almost never be lucrative. For example, originator companies are not able to make commercial gain in researching and developing treatments for children with AIDS, because they have more or less eliminated such cases. The story is the same for tuberculosis, malaria and ebola, and a host of other neglected tropical diseases. Public-private partnerships seem to be leading the way forward for these drugs. Governments undertake some of the risks for drug research by giving tax relief, subsidies or funding research directly. However, there seems to be a growing pile of evidence that drug development for developing countries is mostly driven by national interests. Andrew Lakoff, an anthropologist has highlighted two drives behind global health. Diseases can be tackled to maintain global health security – to protect the developed world from the threat of these infectious diseases or they can be developed as a humanitarian endeavor to stop the entrenchment of poverty. The fight against ebola was declared a global priority when a few foreign doctors and nurses became infected. With regards to ebola, the leading drug that the US has developed, ZMapp, is of interest not because of its commercial viability, but because of its broader use in biodefence. Similarly, research into Hendra, an Australian bat-borne disease that has only killed four people was considered worth the investment. The US military thought that the research would yield defense against the related “weaponisable” Nipah virus, which is classified as a likely bio-terrorism agent.
It is not a complete conspiracy, but a consortium of drug companies, generic drug manufacturers and governments are taking action in their own interest, turning odds against developing countries. Generic drugs are the shortcut to address this problem. Efficiency is nearly always behind the latest originator drug in the market but their research on developing world diseases are the most likely to be appropriated by generic drug companies. However, with the rise of generic medicine, originator companies become even less likely to develop cures for ‘diseases of poverty’, because they would not be able to cover their losses. Which leads to the question, what does the end-game look like?
Self-sufficiency might be the game-changer
In April 2010, Cinpharm-Cameroon opened a modern factory in Douala, in West and Central Africa. . It produces painkillers, antibiotics, anti-malarial, intestinal parasiticids, anti-inflammatory, antibiotics, antiretroviral and tuberculosis drugs. Eventually, the production should meet 25% of national needs. Developments such as these become especially important, as India pivots away from the developing world’s generic medicine needs. Furthermore, drug research and development is firmly embedded within Western interests. To suppress healthcare costs, countries need to self-supply at least some of their own pharmaceutical needs.
Moreover, there are real concerns that the costs of developing a drug have been artificially inflated by originator drug companies to justify their costs. The final costs that drug companies report often include more than just the money they pay ‘out-of-pocket’ but also capital costs. Therefore, they account for both failed experiments and successes in the cost of developing a drug. Yet, it is almost never declared whether official figures include the capital costs. This information is all confidential and voluntarily released, so it is extraordinarily difficult to validate these figures. As pharmaceutical companies begin to outsource their clinical trials to developing countries to offset these costs, it becomes clear that they are responding to the enormous pressure to reduce the costs of healthcare. In many cases, intelligent clinical trial design can prevent false negative results. It is also becoming more important to find the appropriate dose of a drug by comparing it to a placebo as well as the most accepted treatment currently available.
Generic drugs need an initial boost
For now, it seems that developing countries with a high disease burden would need support in terms of technological know-how and experience with running a strong primary healthcare system. As developing nations become better educated and encourage specialisation, it is more likely that they can take the lead on the fight against diseases in their own countries. Generic drugs are also only part of the story. Stories of vaccine stockpiling, and hoarding during the H5N1 virus epidemic serve as examples to show that technology can only bring the horse to the water. Prevention of these diseases is also becoming a public health strategy for governments – mosquito nets and quinine are distributed in equal measure in countries with a high malaria burden. Ensuring that citizens can access healthcare at low cost requires integrated policy actions, transparency, and monitoring and evaluation mechanisms. From that perspective, generic drugs are only a small part of the fight against these diseases.
The global fight against ebola, malaria or dengue needs to be affordable to be fought. Generic drugs may just end up being part of the picture amongst prevention, infrastructure and funding. There are legitimate concerns by originator pharmaceutical companies who are expected to innovate and maintain high levels of safety and effectiveness according to drug safety regulations. One question is whether the moral, economic and social cost to developing nations to protect their privilege is justified. Generic drugs have already changed the healthcare landscape beyond recognition with very obvious short-term benefits for developing countries. Despite this, political trends seem to point to more intellectual property laws, not a relaxation of them. There are moral and practical considerations to be made, and generic drugs may simply be caught in the political crossfire. It is time their huge advantages are recognized.