“The miserable have no other medicine, but only hope:
I've hope to live, and am prepared to die.”
William Shakespeare, Measure for Measure
Noncommunicable diseases (NCDs) caused more than one-half of global deaths in 2008 (and 80% of these occurred in low- and middle-income countries). Cancer, leading to more than 7.1 million deaths yearly and exceeding those caused by tuberculosis, human immunodeficiency virus/acquired immunodeficiency syndrome, and malaria combined, is the most significant cause of lost years of life and productivity worldwide.
Access to medications in general—and cancer treatments in particular—is one of the major challenges facing oncology and public health practitioners today, especially in countries with limited resources. Drug development is slow and expensive; it may take a decade or longer, the screening of thousands of compounds, and capitalized costs of approximately $1.8 billion to bring a new medication to market. As such, we grant patents, which give manufacturers a period of exclusive rights to sell a new drug, as incentive for innovation and the discovery and development of drugs. Once a patent expires, other companies can make and market a once-exclusive branded agent, as long as their product is bio-equivalent.
Generic competition then sets in, and the price of medications usually drops significantly, often by 80% or more, allowing access to a larger number of patients. We recently published a special supplement on generics and biosimilars in the Annals of Oncology, including a paper providing a cost comparison between the most frequently used generic and originator chemotherapy drugs in India: paclitaxel, gemcitabine, docetaxel, oxaliplatin, and irinotecan, highlighting and discussing the economic implications of generic substitution in common cancers in the country. The average sales cost of generic drugs was 64%-91% lower than that of the respective originator-branded drug. Moreover, there were significant cost savings per cycle and per patient, ranging from ~INR (Indian rupees) 11,000 to >INR 90,000 ($200-$1,600, €160-€1,300) and from ~INR 50,000 to >INR 240,000 ($900-$4,300, €700-€3,400), respectively. Overall, potential yearly savings for health systems in India were nearly INR 47 billion (~$843 million, €670 million). These numbers are clearly significant in a country with a gross national income per capita of less than $1,500 at current exchange rates, and which had expenditures of only $54 per capita in health in 2010.
Major challenges for the greater penetration of generics include public and health care worker perception and quality issues. In a survey of 839 physicians, for instance, nearly a quarter had a negative perception of the efficacy and 50% of the quality of generic medications. Furthermore, there have been reports of low quality substitutes in oncology in low- and middle-income countries. For example, a study in Iraq showed that a significant proportion of patients with chronic myelogenous leukemia lost hematologic, cytogenetic, and molecular control after switching from branded to generic imatinib. Quality assurance with the use of good manufacturing practices and adequate supervision by regulatory authorities is of paramount importance to ensure bioequivalence, and therefore the safety and efficacy, of generic medications.
A systematic review and meta-analysis of 38 randomized, controlled trials comparing generic and branded cardiovascular drugs confirmed their clinical equivalence. Little has been published about the safety, efficacy, and economic implications of the use of generic oncology medications, however, especially in low- and middle-income countries, and this gap clearly needs to be filled by further studies. Investigators from India, with grant support from Fresenius-Kabi, have retrospectively collected clinical data on 393 patients who received generic versions of docetaxel, oxaliplatin, irinotecan, and gemcitabine. The median survival ranged from 12.8 months for patients with lung cancer (66% had metastatic disease), 30 months for patients with colon cancer (67% of patients had metastatic disease), and 47 months for patients with breast cancer (45% had metastatic disease). Between 20% and 45% of patients reported serious adverse events. These data seem to conform to expectations of survival and toxicity but it is clear that the creation of formal registries would help the oncology community have a more precise estimate of the clinical equivalence of generic drugs beyond the bioequivalence required for their marketing approvals.
In conclusion, generic substitution for frequently used chemotherapy drugs in the treatment of common cancers has an enormous potential to generate significant cost savings and increase access to treatment in India and other low- and middle-income countries, but issues of perception and quality need to be addressed if we want the results we see with treatment of cancer in high-income countries spread more evenly across the globe.