Novel thalidomide analogues, “me too” drugs and the Brazilian law / Novos análogos da talidomida, medicamentos “me too” e a lei brasileira

In Brazil, thalidomide has been used virtually without interruption since it was launched as a new and revolutionary sedative drug in 1956. After 1965, when its effi cacy to treat erythema nodosum leprosum (ENL) was discovered, it was regarded as an essential drug because the prevalence of Hansen’s disease is high in the country. In the 1990s and thereafter myriad novel therapeutic uses for thalidomide (autoimmmune diseases, multiple myeloma, aphthous ulcers in AIDS, and others) have emerged owing to its immunomodulatory and antiangiogenic activities. Owing to a marked teratogenicity, however, the prescription and dispensing of thalidomide to patients is strictly controlled in Brazil and elsewhere. Notwithstanding the stringent regulations, a number of post-1965 cases of thalidomide embryopathy have occurred in Brazil. In 2003, a federal law (Law 10.651/2003) prohibited the sale and dispensing of thalidomide in commercial pharmacies. The law, however, made no provision for teratogenic drug analogues such as lenalidomide and pomalidomide, which have been cleared for marketing in the USA, Europe and other countries. Although they are much more expensive than thalidomide, the clinical superiority of novel ana-logues over thalidomide in multiple myeloma and other conditions remains unproven. Therefore, so far novel analogues can be considered as thalidomide “me too” drugs. This author strongly recommends that an amendment to the current law prohibiting the sale and dispensing of thalid-omide in commercial pharmacies be extended to thalidomide analogues. Moreover, we consider that a demonstration of clinical superiority over thalidomide (through gold-standard comparative effi cacy trials) should be an essential requirement for registration of any teratogenic analogue. ---------------------------No Brasil, a talidomida tem sido usada praticamente sem interrupção desde o seu lançamento como novo e revolucionário medicamento sedativo em 1956. Depois de 1965, quando a sua efi cácia para tratar o eritema nodoso (ENL) foi descoberta ela tem sido considerada como medi-camento essencial porque a prevalência da hanseníase é alta no país. Nos anos 1990 e depois, surgiu uma diversidade de novos usos terapêuticos para a talidomida (doenças auto-imunes, mieloma múltiplo, ulcerações aftosas na AIDS, e outras) em virtude das suas atividades anti-infl ammatórias e anti-angiogênicas. Por causa da teratogenicidade, a prescrição e dispensação da talidomida são rigorosamente controladas no Brasil e outros países. Em que pese o rigor da regulamentação, muitos casos de embriopatia pela talidomida ocorreram no Brasil após 1965. Em 2003, uma lei federal (Lei 10.651/2003) proibiu a venda e a dispensação de talidomida em farmácias comerciais. A lei, entretanto, não faz referência aos análogos teratogênicos tais como lenalidomida e pomalidomida cuja comercialização foi autorizada nos EUA, Europa e outros países. Embora sendo muito mais caros que a talidomida, a superioridade clínica dos novos análogos em relação à talidomida no mieloma múltiplo e outras doenças não foi demonstrada. Portanto, até agora os novos análogos podem ser considerados como medicamentos “me too”. Recomenda-se enfaticamente uma emenda à lei atual que estenda a proibição da venda e dispensação em farmácias comerciais aos análogos da talidomida. Deve-se exigir também a demonstração de superioridade clínica em comparação com a talidomida (por meio de ensaios clínicos comparativos de padrão ouro) para registro de qualquer análogo teratogênico

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

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

To be or not to be a carcinogen; delving into the glyphosate classification controversy

The International Agency for Research on Cancer (IARC) placed the most widely used herbicide glyphosate (GLY) into the category 2A (probably carcinogenic to humans), a classification questioned by experts from academia and industry. This article critically appraised the epidemiological and experimental data that led the IARC working group (WG) to consider GLY a probable human carcinogen and the ensuing controversy. An association of GLY with non-Hodgkin lymphoma was suggested by some observational studies. A non-causal explanation for this weak association, however, cannot be excluded. Contrary to WG’s view, long-term rodent assays yielded no convincing evidence that GLY is carcinogenic. The mechanistic evidence remains elusive as well. Bacterial reverse mutation tests (including tester strains sensitive to oxidative mutagens) were clearly negative, and so were rodent genotoxicity assays by oral route. Tests with mammalian cells in vitro yielded conflicting results at high (cytotoxic) concentrations of GLY-based formulations. Conflicting results were also obtained when high doses of GLY-based herbicides were administered to rodents by the intraperitoneal route. Such high doses are unlikely to be attained in realistic scenarios of exposure. Finally, the IARC classification is based on a conjectural hazard, and rational public health interventions must be based on estimated risks

Beneficios de los inhibidores de apetito en la salud a largo plazo permanecen sin comprobación

El aumento de la prevalencia de la obesidad ha convertido la prevención y tratamiento del sobrepeso importante desafío para la Salud Pública. Aunado a la dieta y ejercicio, los medicamentos son necesarios para pacientes que no logran perder peso con los cambios de comportamiento. El objetivo del artículo fue englobar las preocupaciones actuales con la seguridad y la efectividad de medicamentos inhibidores del apetito. Varios anorexígenos fueron eliminados por razones de seguridad. En 2010, la sibutramina fue retirada del mercado porque un estudio de larga duración demostró que ésta aumentaba el riesgo de eventos cardiovasculares. Hasta ahora ningún estudio con número considerable de pacientes demostró que anorexígenos reducen la morbi-mortalidad asociada al sobrepeso. La retirada de sibutramina del mercado muestra que directrices para evaluación de medicamentos anorexígenos deben ser más rigurosas, y que estudios de larga duración sobre los beneficios para la salud deben ser realizados antes de la comercialización.O aumento da prevalência da obesidade tornou a prevenção e tratamento do sobrepeso importante desafio para a Saúde Pública. Além da dieta e exercício, os medicamentos são necessários para pacientes que não conseguem perder peso com as mudanças comportamentais. O objetivo do artigo foi sumarizar as preocupações atuais com a segurança e efetividade de medicamentos inibidores do apetite. Vários anorexígenos foram banidos por razões de segurança. Em 2010, a sibutramina foi retirada do mercado porque um estudo de longa duração mostrou que ela aumentava o risco de eventos cardiovasculares. Até agora nenhum estudo com número expressivo de pacientes demonstrou que anorexígenos reduzem a morbi-mortalidade associada ao sobrepeso. A retirada da sibutramina do mercado mostra que diretrizes para avaliação de medicamentos anorexígenos devem ser mais rigorosas, e que estudos de longa duração sobre os benefícios para a saúde devem ser realizados antes da comercialização.Because of the increasing prevalence of obesity, prevention and treatment of overweight has become a major public health concern. In addition to diet and exercise, drugs are needed for patients who failed to lose weight with behavioral treatment. The current article aimed to summarize recent concerns on the safety and efficacy of appetite suppressants. Several appetite suppressants have been banned for safety reasons. In 2010, sibutramine was withdrawn from the market because a long-term study showed it increased the risks of cardiovascular events. So far no study with a sufficiently large sample size has demonstrated that appetite suppressants can reduce morbidity and mortality associated with overweight. The withdrawal of sibutramine highlights that guidelines for the evaluation of weight control drugs must be more stringent, and studies on their long-term health benefits are needed prior to their marketing

Análise experimental de uma fornalha a lenha de fluxo co-corrente para secagem de grăos /

Inclui apęndicesOrientador : Marcelo Risso ErreraCo-orientador : Thomaz P. F. BorgesInclui bibliografi

Transbordar o habitar: A Praça Grécia como potencializadora de diferentes realidades sociais

O trabalho tem como tema central as interações e barreiras que ocorrem nos espaços livres públicos urbanos, especificamente naqueles inseridos entre diferentes realidades sociais, e como tais espaços podem atuar na promoção de espaços coletivos, com caráter participativo e democrático. Para explorar tais questões, a proposta tem como objeto de análise a Praça Grécia e a Rua Humberto de Campos, localizadas no Leblon, e suas inter-relações com o bairro e, em particular, com o conjunto habitacional Cruzada São Sebastião. O conjunto habitacional foi construído na década de 1950 por iniciativa de Dom Hélder Câmara, com o objetivo de abrigar parte da população da favela da Praia do Pinto, que se situava no Leblon. A Cruzada São Sebastião apresenta um enorme contraste socioeconômico com o contexto urbano do bairro. Essa distância social resulta na falta de apropriação pelos moradores do conjunto das áreas livres existentes no restante do bairro. Assim, a Praça Grécia, que se localiza em frente à Cruzada, se apresenta como um dos poucos locais em que ocorre - mesmo que parcialmente - tal apropriação. Dessa maneira, o projeto visa promover a requalificação da praça e da rua Humberto de Campos a partir do seu entendimento como espaços de apropriação coletiva e de convivência entre diferentes atores sociais

Novel thalidomide analogues, “me too” drugs and the Brazilian law

In Brazil, thalidomide has been used virtually without interruption since it was launched as a new and revolutionary sedative drug in 1956. After 1965, when its efficacy to treat erythema nodosum leprosum (ENL) was discovered, it was regarded as an essential drug because the prevalence of Hansen’s disease is high in the country. In the 1990s and thereafter myriad novel therapeutic uses for thalidomide (autoimmmune diseases, multiple myeloma, aphthous ulcers in AIDS, and others) have emerged owing to its immunomodulatory and antiangiogenic activities. Owing to a marked teratogenicity, however, the prescription and dispensing of thalidomide to patients is strictly controlled in Brazil and elsewhere. Notwithstanding the stringent regulations, a number of post-1965 cases of thalidomide embryopathy have occurred in Brazil. In 2003, a federal law (Law 10.651/2003) prohibited the sale and dispensing of thalidomide in commercial pharmacies. The law, however, made no provision for teratogenic drug analogues such as lenalidomide and pomalidomide, which have been cleared for marketing in the USA, Europe and other countries. Although they are much more expensive than thalidomide, the clinical superiority of novel ana-logues over thalidomide in multiple myeloma and other conditions remains unproven. Therefore, so far novel analogues can be considered as thalidomide “me too” drugs. This author strongly recommends that an amendment to the current law prohibiting the sale and dispensing of thalid-omide in commercial pharmacies be extended to thalidomide analogues. Moreover, we consider that a demonstration of clinical superiority over thalidomide (through gold-standard comparative efficacy trials) should be an essential requirement for registration of any teratogenic analogue.In Brazil, thalidomide has been used virtually without interruption since it was launched as a new and revolutionary sedative drug in 1956. After 1965, when its efficacy to treat erythema nodosum leprosum (ENL) was discovered, it was regarded as an essential drug because the prevalence of Hansen’s disease is high in the country. In the 1990s and thereafter myriad novel therapeutic uses for thalidomide (autoimmmune diseases, multiple myeloma, aphthous ulcers in AIDS, and others) have emerged owing to its immunomodulatory and antiangiogenic activities. Owing to a marked teratogenicity, however, the prescription and dispensing of thalidomide to patients is strictly controlled in Brazil and elsewhere. Notwithstanding the stringent regulations, a number of post-1965 cases of thalidomide embryopathy have occurred in Brazil. In 2003, a federal law (Law 10.651/2003) prohibited the sale and dispensing of thalidomide in commercial pharmacies. The law, however, made no provision for teratogenic drug analogues such as lenalidomide and pomalidomide, which have been cleared for marketing in the USA, Europe and other countries. Although they are much more expensive than thalidomide, the clinical superiority of novel ana-logues over thalidomide in multiple myeloma and other conditions remains unproven. Therefore, so far novel analogues can be considered as thalidomide “me too” drugs. This author strongly recommends that an amendment to the current law prohibiting the sale and dispensing of thalid-omide in commercial pharmacies be extended to thalidomide analogues. Moreover, we consider that a demonstration of clinical superiority over thalidomide (through gold-standard comparative efficacy trials) should be an essential requirement for registration of any teratogenic analogue