Clinical research challenges in rare genetic diseases in Brazil

Abstract

Rare diseases are defined as conditions with a prevalence of no more than 6.5 per 10,000 people. Although each rare disease individually affects a small number of people, collectively, the 6,000 to 8,000 rare conditions (80% of them with genetic cause) affect around 8% of the world’s population. Research about the natural history and underlying pathophysiological mechanisms of rare diseases, as well as clinical trials with new drugs, are important and necessary to develop new strategies for the treatment of these conditions. This report describes the experience of a clinical research group working with rare diseases in a reference center for lysosomal diseases in Brazil (Medical Genetics Service, Hospital de Clínicas de Porto Alegre). The activities of this research group enabled its participation in several international multicenter clinical research protocols related to the natural history or therapy development for rare genetic diseases. This participation has allowed the development of personal skills and institutional facilities for clinical research. The clinical research developed in our center has raised the quality of the medical assistance provided to non-clinical research patients in addition to enabling early access to new therapies to many patients with orphan conditions.

Cafe-au-lait spots as a clinical sign of syndromes

“…Genetic disorders account for approximately 80% of all rare diseases (Giugliani et al, 2019). All syndromes associated with the presence of CALM listed here are rare.…”

“…Within health systems, rare diseases have been defined based on the criteria of prevalence or number of affected individuals. According to the European Union, rare diseases are defined as those that affect less than 1 in 2,000 people (Giugliani et al, 2019). For the World Health Organization, a rare disease is one that affects up to 65 people in 100,000 individuals or 1.3 people in every 2,000 individuals.…”

Clinical trials for genetic diseases in Latin America

“…These legislations were responsible for a marked increase in the development of drugs for rare diseases by pharmaceutical companies, although concerns about misuse of legislation to obtain profit without developing any new compound and concerns regarding monopolization and disproportional high prices for orphan drugs were also raised (Garattini et al, 2015;Murphy et al, 2012). In the Latin American context, two recent resolutions issued in 2017 by the Brazilian Health Regulatory Agency- Anvisa (2017) and National Health Council (Conselho Nacional de Saúde, 2017) established special procedures for the approval of clinical trials and registration/manufacturing of investigational products for rare diseases, and exempted ultra-rare diseases from the previous requirement of life-long poststudy supply of the investigational product (L. Giugliani et al, 2019), inducing an increase in the number of clinical trials being conducted for these disorders in Brazil.…”

“…( (Giugliani et al, 2019). In many Latin American countries, CRO associations also contribute with the development of clinical research in the region, by providing training for professionals and interacting with the community and regulatory authorities (Ukwu et al, 2011).…”

Rare diseases in Chile: challenges and recommendations in universal health coverage context

“…Unlike the EU, that established a single prevalence for all its member states, in Latin America there is no consensus definition of RDs and each country uses a definition through its own national regulations or public policies. For instance, Mexico and Argentina use the EU definition, in Brazil, a rare disease is defined as one affecting fewer than 65 out of 100,000 individuals, and Peru, Chile and other countries have no clear definition of RDs [2][3][4][5][6][7][8]. A summary of individual South American country's definition of RD and laws can be found in Fig.…”