genglob magazine

In 2005 more than 11 million new cases of cancer were diagnosed and more than 7 million people died (accounting for approximately 13% of global deaths) from this devastating disease – over 70% of whom live in low- and middle-income countries. In 2020, if current trends continue, new cancer cases will increase to 16 million per year and more than 10 million people will die; between 2005 and 2015, it is projected that 84 million people will die of cancer.  The absolute number of cases of cancer in persons younger than 50 years old is not predicted to increase in the next 50 years, but the absolute number of cases in persons aged 65 years and older is expected to double between 2000 and 2030.

Cancer is mostly treated using a combination of surgery, radiotherapy and systemic treatment, including cytotoxic drugs, hormonal therapy, or targeted treatment approaches. The latter include monoclonal antibodies or “small molecule” drugs that bind to more or less tumour-specific molecules (i.e., particular molecules present in or on the tumour cells and (ideally) not present, on normal cells) and in doing so, block the processes of carcinogenesis, tumour growth or spread. Because of their specificity for cancer cells, particularly if directed towards the molecular lesions that give rise to cancer (which are not present in normal cells), such molecules will have large benefits in terms of reduced toxicity compared to non-specific cytotoxic drugs. Drugs, a word applied here to all such systemic therapies, have for long played a central role in the treatment of some cancers, such as leukemias, lymphomas, testicular cancers and childhood cancers, and in recent years have played an increasingly important role in the management of many other cancers, usually in conjunction with surgery and/or radiation therapy, albeit, their value varies greatly from one cancer to another. Unfortunately, many patients worldwide do not have access to the drugs they need. This is part of a broader problem of access to optimal cancer care, which remains a significant challenge in many parts of the world.

Cancer drugs: the facts

• In 2006, global pharmaceutical sales across all disease areas grew 7% to $643 billion – 87% of sales were in North America, Europe and Japan. It is estimated that the global pharmaceutical market will more than double in value to $1.3 trillion by 2020.
• Sales of cancer drugs reached $34.6 billion in 2006, which represents a 20.5% increase in sales over the previous year; cancer drug sales are now ranked second, after lipid regulators, . Expenditure on cancer drugs account for between 10-20% of spending on cancer care and about 5% of total drugs expenditure.
• Worldwide, industry sales are projected to continue to grow strongly at 7 per cent per annum over the next five years. Espicom Business Intelligence estimate that the annual sales of pharmaceuticals will reach US$892.6 billion in 2008 and project that it will reach US$1,247.7 billion in 2013. The markets driving this change will be:
  • Central/Eastern Europe, with 9.5 per cent growth per annum;
  • The Americas, with 8.4 per cent growth per annum;
  • Middle East and Africa, with 6.4 per cent growth per annum;
  • Asia/Pacific, with 5.5 per cent growth per annum; and
  • Western Europe, with 5.0 per cent growth per annum.:
• Sales of generic drugs are increasing – last year sale of these drugs represented over half of the drugs sold in 7 of the leading pharmaceutical markets worldwide. Generic versions of a number of commonly used cancer drugs are widely available. A number of cancer drugs are set to lose their patents in the near future, and it is likely therefore that over the coming years sales of generic cancer drugs will increase.
• Innovative cancer drugs are developed as a result of both public and private investment in cancer research. It has been estimated that the pharmaceutical industry spends between $6.5 – 8 billion per year on cancer research. Public investment (ie. Governmental and charitable) in the development of cancer drugs is much lower and therefore, drug development is mainly driven by commercial considerations rather than public health priorities. This means that there is less investment in the development of drugs to treat rarer cancers with few or no available treatment options, or in rare cancers, such as childhood cancers. This is likely to change to some degree as drug development is increasingly focused on targeted therapies, since most targets are confined to one or a small number of cancers. It is inevitable, however, that the very large difference in incident cases in various cancers, for example, breast or lung cancer versus retinoblastoma or specific sarcomas, will continue to influence decisions with respect to product development.
• Currently over 380 compounds are in development for cancer, and half of those in the late stages development are targeted therapies. While the more limited toxicity of such molecules should eventually reduce the total cost of cancer treatment, the price of the targeted therapies (all patented) that have made it to the market to date has been set very high and prices continue to increase dramatically. The industry claims that their pricing policy reflects the cost and risk involved in research particularly in the development of new drugs, many of which never make it to the market. However, some of these so called innovative drugs are “me too” products (i.e. only slightly modified compounds in comparison to established precursor drugs) and often (although there are exceptions) have small benefits – measured, for example, in terms of a few months increase in survival, such that the high prices set for them are generally not justifiable. For these and other reasons, the pharmaceutical industry has been accused of lacking transparency in its approach to pricing of innovative drugs.
• Other factors may greatly influence price – for example, some targeted therapies may need to be administered over long periods in order to maintain cancers in a quiescent stage, which will have a significant effect on the cost of treatment. It is clear that while still under patent protection, targeted drugs will increase the overall cost of cancer care will increase significantly and most targeted therapies will be unaffordable for low and middle income countries, and even create major financial problems in the highest income countries. At the present time, however, the overall contribution from targeted therapies to cancer control remains small. Moreover, patients in low and middle income countries currently have difficulty in affording even traditional cytotoxic drugs, particularly in diseases where treatment may last for years (such as in acute lymphoblastic leukemia and breast cancer treated with anti-hormonal therapies).  Finally, targeted drugs require demonstration of the presence of the target in or on the tumour cells, requiring high quality laboratory services, which are not always available in developing countries, or not affordable by patients. Thus, targeted therapies, in countries with limited resources are presently a controversial health priority.

Access to cancer drugs

Worldwide access to cancer drugs is extremely unbalanced: whereas it is usually covered by health care systems in developed countries, in low and middle income countries only a small fraction of the population has insurance; the remainder must pay out of pocket and, if they cannot afford it, may not receive treatment at all.

Cancer drugs can improve outcomes when they are available, affordable, of assured quality and properly used. However, the World Health Organization (WHO) estimates that nearly one third of the world’s population does not have access to full and effective treatment with the medicines they need – this rises to over 50% in the poorest parts of the world. Even in highly developed countries access to some drugs and to the best available therapy is not guaranteed for everyone. There are a number of reasons for this, including:

1. Drug costs – even standard cytotoxic drugs as listed, for example, in the WHO list of Essential Cytotoxic Drugs are out of reach of the poorest patients, while the high price of patent-protected cancer drugs makes them unaffordable for many countries. Patent enforcement by pharmaceutical companies in low and middle income countries, therefore, can totally inhibit access.
2. Insufficient public funding of health – governments in many countries do not provide reimbursement for essential cancer drugs.
3. Restrictive regulations – the cost of importing drugs, including duties, taxes, fees and distribution costs may grossly inflate the prices of standard drugs.
4. Poor infrastructure – many countries lack the facilities necessary to enable complex cancer drug regimens to be administered safely and effectively
5. Irrational use of cancer drugs – There is a dearth of adequately trained health professionals who are competent to prescribe and administer cancer drugs. In addition, many countries lack national evidence-based treatment guidelines from which a national Essential Drugs List would logically follow. Guidelines developed in the USA and Europe, for example, may not be suitable in low resource settings for reasons of cost, drug availability, limitations in supportive and nursing care, etc., but many oncologists in low and middle income countries use such guidelines, at least in modified form, even when they contain drugs that provide minimal if any benefit at a substantially higher cost. Paradoxically, this may result in more expensive analogues with little or no advantage being purchased, while more affordable and often equally effective drugs in a developing country setting (although there are few comparisons of this type in the literature) are unavailable.
6. Bureaucratic policies – In many countries worldwide national opiate policies are too restrictive, which limits availability to morphine and other pain-relieving drugs. Frequently doctors are afraid to prescribe opioids, have misconceptions about their use or do not employ the principle of prevention of symptoms in the practice of palliative.  It is estimated that 80% of cancer patients who suffer severe pain have no access to opiates and many more have limited or inadequate access.
7. Counterfeit medicines – The global market in fake drugs that range from those containing harmful toxic substances to those with inactive, useless ingredients or those which contain only a fraction of the stated quantity of the active ingredient is increasing at a rapid pace. Counterfeiting is greatest in those regions where regulatory and legal oversight is weakest. In developed countries sales of counterfeit drugs represent less than 1% of the pharmaceutical market. This rises to 10-30% in parts of Asia and Latin America and up to 70% in some African countries. Some pharmaceutical companies have established drug donation programmes to address access problems in low-income countries. Although useful in the short-term these programmes are not a long-term solution to cancer drug access.

WHO has developed a list of essential cancer medicines, which is updated and revised biennially. This list provides a foundation for the development of national essential drug lists based on the prevailing pattern of cancer in the country as well as economic considerations. However, while most countries can afford to purchase these drugs, poor procurement practices may result in intermittent availability (or availability, when out of stock in a public hospital, via the private sector at greatly increased cost). Patients may not be able to afford the drugs when they must pay out of pocket.

Large pharmaceutical companies can grant voluntary licenses to governments in low-income countries to facilitate the production of of generic versions of innovative cancer drugs. This would not affect the bottom line of large companies, as their primary market is developed world for such drugs. This would also bring in the necessary competition and price within the reach of common people in such countries.