Dynamics of patents, orphan drug designation, licensing, and revenues from drugs for rare diseases: The market expansion of eculizumab.

BACKGROUND: This study examines the dynamics of the eculizumab patenting, orphan designation, and marketing authorization process in different countries and regulatory systems and analyzes drug revenues since its first marketing authorization. METHODS: A retrospective case study was conducted. Multiple information sources were used to: determine the status of eculizumab patents; examine the designation of orphan drug status by US, European, Japanese, and Brazilian regulatory authorities to determine registration status and approved clinical indications; estimate the prevalence of associated clinical conditions; investigate the history of the drug manufacturer, Alexion Pharmaceuticals, Inc., and its financialized business model; and examine global eculizumab sales revenues since its first marketing authorization. RESULTS: Our search yielded 32 patent families divided into 98 applications. The first patent granted was filed in 1995 by Alexion Pharmaceuticals, Inc. in the US. Eculizumab has always been as an orphan drug, except in the Brazilian regulatory agency. All clinical indications approved thus far refer to rare diseases (e.g., paroxysmal nocturnal hemoglobinuria syndrome, atypical hemolytic-uremic syndrome, refractory and generalized myasthenia gravis, and neuromyelitis optica spectrum disorder). Alexion's revenues amounted to more than US$25 billion between 2007 and 2019, showing a growing trend. Eculizumab led sales from the beginning, being the only product in the company's portfolio until 2015. In 2019, the drug accounted for 79.1% of all revenues. DISCUSSION: Our findings show that a strategy focused on obtaining orphan drug designation, expanding therapeutic indications and the geographic range of marketing approvals, extending monopoly periods, and prioritizing public procurement niches has enhanced revenues and helped the company achieve leadership in a highly specific and profitable market.

Government funding of cancer research in Brazil.

BACKGROUND: Cancer research is a prominent theme on national and international development agendas. In many developed countries, funding for this area comes mainly from government sources. This article analyzes government funding of cancer research in Brazil, identifying the main funding instruments and examining the regional distribution of resources, research project and researcher profiles. METHODS: Exploratory study of government funding of cancer research in Brazil between 2007 and 2016. The primary data were federal and state funding agencies. RESULTS: A total of 8565 research awards were identified for the period 2007-2016. Amounting to almost US$489 million, these awards were linked to 7622 research projects and 3068 researchers. The proportion of grants awarded to women was slightly higher. It is noteworthy that just 3% of researchers received 20 % of the grants. The multiple-grant history of individual researchers seemed to be a conditioning factor for obtaining new grants/fellowships. Funding was highly concentrated in the Southeast region, accounting for 84.4 % of total awards. There was a positive correlation between number of awards and amount awarded. The most frequently studied cancers were breast (11.8 %), head and neck (9.0 %) and skin cancer (5.3 %). Studies that did not specify the type of cancer accounted for 36.8 % of grants and 45.1 % of funding. CONCLUSION: The findings show a fall in the share of cancer research funding in the three largest funders. Cuts in government spending triggered by the country's political and economic crisis, highlight the vulnerability of science and technology. Greater transparency through access to information on funding, researcher, and research profiles is key to obtaining a better understanding the cancer research funding landscape in Brazil and reducing regional inequalities. POLICY SUMMARY: A more centralized management of public cancer research funding and constant investment and monitoring is needed to ensure the effective implementation of funding policy.

The Zika Virus Outbreak in Brazil: Knowledge Gaps and Challenges for Risk Reduction.

We analyzed uncertainties and complexities of the Zika virus outbreak in Brazil, and we discuss risk reduction for future emergencies. We present the public health situation in Brazil and concurrent determinants of the epidemic and the knowledge gaps that persist despite building evidence from research, making public health decisions difficult. Brazil has adopted active measures, but producing desired outcomes may be uncertain because of partial or unavailable information. Reducing population group vulnerabilities and acting on environmental issues are medium- to long-term measures. Simultaneously dealing with information gaps, uncontrolled disease spread, and vulnerabilities is a new risk scenario and must be approached decisively to face emerging biothreats.

Trends in medicines procurement by the Brazilian federal government from 2006 to 2013.

The costs of medicines pose a growing burden on healthcare systems worldwide. A comprehensive understanding of current procurement processes provides strong support for the development of effective policies. This study examined Brazilian Federal Government pharmaceutical procurement data provided by the Integrated System for the Administration of General Services (SIASG) database, from 2006 to 2013. Medicine purchases were aggregated by volume and expenditure for each year. Data on expenditure were adjusted for inflation using the Extended National Consumer Price Index (IPCA) for December 31, 2013. Lorenz distribution curves were used to study the cumulative proportion of purchased therapeutic classes. Expenditure variance analysis was performed to determine the impact of each factor, price and/or volume, on total expenditure variation. Annual expenditure on medicines increased 2.72 times, while the purchased volume of drugs increased 1.99 times. A limited number of therapeutic classes dominated expenditure each year. Drugs for infectious diseases drove the increase in expenditures from 2006 to 2009 but were replaced by antineoplastic and immunomodulating agents beginning in 2010. Immunosuppressants (L04), accounted for one third of purchases since 2010, showing the most substantial growth in expenditures during the period (250-fold increase). The overwhelming price-related increase in expenditures caused by these medicines is bound to have a relevant impact on the sustainability of the pharmaceutical supply system. We observed increasing trends in expenditures, especially in specific therapeutic classes. We propose the development and implementation of better medicine procurement systems, and strategies to allow for monitoring of product price, effectiveness, and safety. This must be done with ongoing assessment of pharmaceutical innovations, therapeutic value and budget impact.