Desafíos en el empleo de los medicamentos huérfanos

Las enfermedades raras son aquellas que tienen baja prevalencia y que, por lo tanto, el desarrollo de medicamentos para tratarlas no es rentable para las empresas farmacéuticas debido a la baja demanda. A pesar de que ya se cuenta con diferentes políticas públicas alrededor del mundo para incentivar a las industrias farmacéuticas a investigar estos medicamentos, conocidos como medicamentos huérfanos, su desarrollo conlleva muchas dificultades en las evaluaciones clínicas y el precio final para el público es muy elevado. Si bien en años recientes se ha planteado el uso de tecnología de impresión en 3D para producir estos medicamentos o incluso recurrir a otros medicamentos previamente aprobados para tratar enfermedades raras, existe un historial de mal uso de las legislaciones por parte de las empresas con el fin de generar beneficios comerciales, por lo que estas políticas deben reforzarse para que cumplan su propósito; ayudar a una población muy vulnerable. El objetivo del presente texto es exponer los resultados de una revisión documental sobre el panorama científico y sociopolítico en el que se encuentra el problema de las enfermedades raras y los medicamentos huérfanos, así como las posibles soluciones que se están desplegando para abordarlo. Deriva de un estudio que se desarrolla en el momento actual en la Universidad Autónoma Metropolitana, de Ciudad de México.

The strange illnesses are those that have low prevalence and that, therefore, the development of medications to treat them is not profitable for the pharmaceutical companies due to the drop demands. Although it is already counted with different political public around the world to motivate to the pharmaceutical industries to investigate these medications, well-known as orphan medications, their development bears many difficulties in the clinical evaluations and the final price for the public it is very high. Although in recent years he/she has thought about the use of impression technology in 3D to produce these medications or even to appeal to other medications previously approved to treat strange illnesses, a record of wrong use of the legislations exists on the part of the companies with the purpose of generating commercial benefits, for what these politicians should be reinforced so that they complete its purpose; to help a very vulnerable population. The objective of the present text is to expose the results of a documental revision on the scientific and sociopolitical panorama in which is the problem of the strange illnesses and the orphan medications, as well as the possible solutions that they are spreading to approach it. It derives of a study that is developed in the current moment in the Metropolitan Autonomous University, of Mexico City.

Research advances in pharmacotherapy for rare diseases in children / 中国当代儿科杂志

There are more than 7 000 rare diseases and approximately 475 million individuals with rare diseases globally, with children accounting for two-thirds of this population. Due to a relatively small patient population and limited financial resources allocated for drug research and development in pharmaceutical enterprises, there are still no drugs approved for the treatment of several thousands of these rare diseases. At present, there are no drugs for 95% of the patients with rare diseases, and consequently, the therapeutic drugs for rare diseases have been designated as orphan drugs. In order to guide pharmaceutical enterprises to strengthen the research and development of orphan drugs, various nations have enacted the acts for rare disease drugs, promoted and simplified the patent application process for orphan drugs, and provided scientific recommendations and guidance for the research and development of orphan drugs. Since there is a relatively high incidence rate of rare diseases in children, this article reviews the latest research on pharmacotherapy for children with rare diseases.

Resistência a Antimicrobianos: a formulação da resposta no âmbito da saúde global / Antimicrobial Resistance: formulation of the response in the global health context

RESUMO A Resistência a Antimicrobianos (AMR) tem se revelado como um dos maiores problemas para a saúde pública no nível global. O objetivo deste artigo foi analisar a formulação da resposta à AMR negociada no âmbito da Organização Mundial da Saúde (OMS) por seus Estados-Membros. Foram analisados os relatórios e resoluções produzidos na Assembleia Mundial da Saúde no período de 1998 a 2019. Os achados indicam que, a partir de 2014, foram estabelecidas condições de possibilidade para a aprovação do Plano de Ação Global em AMR de forma mais robusta, abrangendo o conceito de Saúde Única e envolvendo outras instâncias internacionais (FAO, OIE, OMC e PNUMA). A análise dos conteúdos e o uso de diferentes referenciais analíticos, considerando dois setores econômicos - agropecuária e indústria farmacêutica -, mostraram-se relevantes para ilustrar a complexidade da temática, reforçando sua relevância global, reconhecendo a dimensão do uso de antibióticos em animais e as lacunas em inovação tecnológica. Como a OMS, além de ser um importante agente mobilizador para a resposta à AMR no nível global, tem garantido orçamento para ações nessa área mesmo em um contexto de desfinanciamento, conclui-se que a perspectiva da saúde pública deve prevalecer na resposta à AMR.

ABSTRACT Antimicrobial Resistance (AMR) has proved to be a major public health problem at the global level. This paper examined the formulation of the response to AMR negotiated through the World Health Organization (WHO) by its Member States. Related WHO reports and resolutions from 1998 to 2019 were analysed. The findings indicate that, from 2014 on, more robust conditions were established for approval of a Global Action Plan on AMR, encompassing the concept of One Health and involving other international entities (FAO, OIE, WTO and Unep). Content analysis and various analytical frameworks, considering two economic sectors (the livestock and pharmaceutical industries), proved relevant to illustrating the complexity of the issue, reinforcing its global importance and acknowledging the extent of antibiotic use in animals and the gaps in technological innovation. As the WHO is not only an important agent for mobilizing the response to AMR at the global level, but - despite a context of de-funding - has guaranteed a budget for action in this area, it is concluded that the public health perspective should prevail in the response to AMR.

The case of eculizumab: litigation and purchases by the Brazilian Ministry of Health / O caso do eculizumabe: judicialização e compras pelo Ministério da Saúde

ABSTRACT OBJECTIVES This study examined the purchases of eculizumab, a high-cost monoclonal antibody used in the treatment of rare diseases by Brazilian federal agencies, in terms of purchased quantities, expenditures, and prices. METHODS Eculizumab purchases made between March 2007 and December 2018 were analyzed, using secondary data extracted from the Federal Government Purchasing System (SIASG in Portuguese). The following aspects were assessed: number of purchases, purchased quantities, number of daily doses defined per 1,000 inhabitants per year, annual expenditures, and prices. The prices were adjusted by the National Broad Consumer Price Index for December 2018. Linear regression was used for trend analysis. RESULTS All acquisitions by federal agencies were made by the Brazilian Ministry of Health. The purchases began in 2009 with tender waiver to comply with legal demand. There was an increasing trend in the number of purchases and quantities acquired over time. Two hundred and eighty-three purchases were made, totaling 116,792 units purchased, 28.2% of them in 2018. The adjusted total expenses summed more than R$ 2.44 billion. After market approval by the Brazilian Health Regulatory Agency, the weighted average price fell approximately 35%, to values under the Medicines Market Chamber of Regulation established prices. CONCLUSION Eculizumab represented extremely significant expenditures for the Brazilian Ministry of Health during the period. All purchases were made to meet demands from lawsuits, outside the competitive environment. The market approval of eculizumab promoted an important price reduction. This study indicates the relevance of licensing and the need for permanent monitoring and auditing of drug purchases to meet legal demands.

RESUMO OBJETIVOS O estudo examinou as aquisições de eculizumabe, um anticorpo monoclonal de alto custo utilizado no tratamento de doenças raras, pelos órgãos federais brasileiros, em termos das quantidades compradas, gastos e preços. MÉTODOS Foram analisadas compras de eculizumabe realizadas entre março de 2007 e dezembro de 2018, por meio de dados secundários extraídos do sistema de compras do governo federal (Siasg). Foram examinados o número de compras, quantidades adquiridas, número de doses diárias definidas por 1.000 habitantes por ano, gastos anuais e preços praticados. Os preços foram corrigidos pelo índice nacional de preços ao consumidor amplo para dezembro de 2018. Regressão linear foi utilizada para análises de tendência. RESULTADOS Todas as aquisições por órgãos federais foram realizadas pelo Ministério da Saúde. As compras se iniciaram em 2009, sendo efetuadas por dispensa de licitação e para atendimento de demanda judicial. Houve tendência crescente no número de compras e quantidades adquiridas ao longo do tempo. Foram realizadas 283 compras, totalizando 116.792 unidades adquiridas, 28,2% compradas em 2018. Os gastos totais contratados corrigidos somaram mais de R$ 2,44 bilhões. Após a aprovação do registro pela Agência Nacional de Vigilância Sanitária, o preço médio ponderado caiu aproximadamente 35%, para valores abaixo dos preços estabelecidos pela Câmara de Regulação do Mercado de Medicamentos. CONCLUSÃO O eculizumabe representou gastos extremamente significativos para o Ministério da Saúde no período. Todas as compras foram feitas para atendimento de demandas judiciais, fora do ambiente competitivo. Seu registro promoveu queda importante nos preços praticados. O estudo aponta a relevância do registro sanitário e da necessidade de monitoramento e auditoria permanentes das compras de medicamentos para atendimento de demandas judiciais.

Pharmaceutical lobbying in Brazil: a missing topic in the public health research agenda

ABSTRACT In the US, where registration of lobbyists is mandatory, the pharmaceutical industry and private health-care providers spend huge amounts of money seeking to influence health policies and government decisions. In Brazil, where lobbying lacks transparency, there is virtually no data on drug industry expenditure to persuade legislators and government officials of their viewpoints and to influence decision-making according to commercial interests. Since 1990, however, the Associação da Indústria Farmacêutica de Pesquisa (Interfarma - Pharmaceutical Research Industry Association), Brazilian counterpart of the Pharmaceutical Research and Manufacturers of America (PhRMA), main lobbying organization of the US pharmaceutical industry, has played a major role in the advocacy of interests of major drug companies. The main goals of Interfarma lobbying activities are: shortening the average time taken by the Brazilian regulatory agency (ANVISA) to approve marketing authorization for a new drug; making the criteria for incorporation of new drugs into SUS (Brazilian Unified Health System) more flexible and speeding up technology incorporation; changing the Country's ethical clearance system and the ethical requirements for clinical trials to meet the need of the innovative drug industry, and establishing a National Policy for Rare Diseases that allows a prompt incorporation of orphan drugs into SUS. Although lobbying affects community health and well-being, this topic is not in the public health research agenda. The impacts of pharmaceutical lobbying on health policies and health-care costs are of great importance for SUS and deserve to be investigated.

Fornecimento do medicamento pós-estudo em caso de doenças raras: conflito ético / Sources of post-study medication in cases of rare disease: ethical conflict / Provisión del medicamento post-estúdio em el caso de enfermidades raras: conflito ético

Partindo da definição e compreensão dos conceitos relacionados ao medicamento, às doenças raras e à ética, bem como à interface entre esses conceitos no bojo da reflexão do direito sanitário, são detalhadas e discutidas as excepcionalidades das drogas, destinadas a tratar doenças raras, definidas por padrões epidemiológicos nacionais e internacionais, como aquelas que afetam poucos indivíduos, proporcionalmente. Em seguida, examina-se o debate internacional acerca do fornecimento de medicamento pós-estudo, para concluir com a evocação do necessário compromisso ético.

Taking off from a definition and comprehension of concepts related to medication, rare diseases and ethics, as well as the interface of these concepts in the core of reflection on sanitary law, the details and exceptionalities of the orphan drugs, designed to treat rare diseases, defined by domestic and international epidemiological standards as those that proportionally affect few individuals. Below, we examine the international debate concerning the supply of medication post-study, to conclude by evoking the required ethical commitment.

Partiendo de la definición y la comprensión de los conceptos relacionados al medicamento, a las enfermedades raras y a la ética, así como a la interfaz entre estos conceptos en el nudo de la reflexión del Derecho Sanitario, son detalladas y discutidas las excepcionalidades de las drogas, destinadas a tratar enfermedades raras, definidas por patrones epidemiológicos nacionales e internacionales como aquellas que afectan a pocos individuos, proporcionalmente. Posteriormente, se examina el debate internacional a propósito de la provisión de medicamentos post-estudio, para concluir con la evocación del requerido compromiso ético.

The Use of Orphan Drugs for Infectious Disease: Current Status and Unmet Needs / 대한내과학회지

BACKGROUND/AIMS: The aim of this study was to investigate the inconveniences and potential improvements in the use of orphan drugs for the treatment of infectious diseases, as determined by a survey of medical professionals. METHODS: An email was sent twice to the members of the Korean Society for Chemotherapy, and an online survey was conducted. The data collected were analyzed in terms of the frequency of drug use and associated difficulties as well as the scope for improvement. RESULTS: A total of 77 medical professionals participated in this survey. Rabies vaccine (n = 52), rabies immunoglobulin (n = 47), and foscarnet injection (n = 43) were supplied mainly through the Korea Orphan Drug Center (KODC), while artesunate (n = 29), quinine sulfate capsule (n = 24), quinine dihydrochloride injection (n = 23), and quinidine gluconate injection (n = 21) were supplied mainly through the National Medical Center (NMC). Difficulties in obtaining orphan drugs through the KODC were related to the KODC drug retrieval system (n = 67, 95.7% of respondents), lack of supplies on holidays (n = 66, 94.3%), complicated application procedures and documents (n = 61, 87.1%), and shipping inconveniences (n = 61, 87.1%). With regard to the use of orphan drugs supplied through the NMC, 52 participants (98.1%) responded that a staff visit should be mandatory for obtaining the drugs. CONCLUSIONS: Antivirals and antimalarial drugs are major orphan drugs used for the treatment of rare infections. It is necessary to establish a more efficient system to ensure a stable supply of orphan drugs, including on holidays, to enhance the smart drug searching system, and to simplify related administrative procedures.