Drug repurposing for rare: progress and opportunities for the rare disease community.

Repurposing is one of the key opportunities to address the unmet rare diseases therapeutic need. Based on cases of drug repurposing in small population conditions, and previous work in drug repurposing, we analyzed the most important lessons learned, such as the sharing of clinical observations, reaching out to regulatory scientific advice at an early stage, and public-private collaboration. In addition, current upcoming trends in the field of drug repurposing in rare diseases were analyzed, including the role these trends could play in the rare diseases' ecosystem. Specifically, we cover the opportunities of innovation platforms, the use of real-world data, the use of artificial intelligence, regulatory initiatives in repurposing, and patient engagement throughout the repurposing project. The outcomes from these emerging activities will help progress the field of drug repurposing for the benefit of patients, public health and medicines development.

Drug repurposing: From the discovery of a useful pharmacological effect to making the treatment available to the patient.

The repurposing of a medicine already on the market to a new indication could be an opportunity to respond rapidly to a therapeutic need not yet covered, particularly in the context of rare and neglected diseases, or health emergencies. However, at each stage, difficulties may arise that will prevent the repurposed drug from being provided to patients. Beyond fortuity or a systematic strategy to detect a useful pharmacological effect, the implementation of the preclinical and clinical stages is sometimes complicated by the difficulty of accessing the molecule and its pharmaceutical data. Furthermore, relevant clinical results will not always be sufficient to ensure that a marketing authorisation is obtained or that patients receive satisfactory care. In addition to describing these various obstacles, the round table provided an opportunity to put forward recommendations for overcoming them, in particular the creation of a public-private partnership structure with sufficient funding to be able to offer individualised support for projects up to and including the marketing application.

Drug repurposing in rare diseases: Myths and reality.

While nearly 8000 rare diseases have been identified, only 5 percent have licensed treatments. As most of these diseases are life threatening, it underscores the urgent need for new drugs. Drug repurposing (also called drug repositioning) consists in identifying new uses for approved or investigational drugs that are outside the scope of the original medical indication. It represents an opportunity for rare diseases and patients with unmet needs. It is an alternative option in drug development and is often presented as being a viable, risk-managed strategy for pharmaceutical companies developing orphan drugs. Drug repurposing is presented as offering various advantages over developing an entirely new drug for a given indication: fewer risks, lower costs and shorter timelines. However, matters are not as simple as this. There are notable successes for drug repurposing. Nevertheless, repurposing does not always succeed. The repurposed drug may fail to demonstrate a benefits-harms balance in clinical trials. Moreover, there are legal and regulatory issues which are specific barriers to drug repurposing and which have to be carefully analyzed before any development of repurposed drugs. The objective of this article is to identify major challenges and opportunities of drug repurposing in rare diseases and to separate fact from fiction.

Drug repositioning for rare diseases: Knowledge-based success stories.

While more than 7000 rare diseases have been identified, only about 5 percent benefit from a licensed treatment. As the majority of these diseases is life threatening, these facts underscore the need for new drugs. Drug repositioning is an alternative strategy in drug development, which represents an attractive opportunity for rare diseases. Drug repositioning (also called drug repurposing, drug reprofiling or drug re-tasking) consists in identifying for an already approved or investigational drug a new use outside the scope of the original medical indication. Drug repositioning is considered in the field of orphan drugs as being a faster and somehow less costly strategy than traditional new drug development for pharmaceutical companies. While several successful repositioning cases have been discovered by serendipity, most successes straightly derive from the molecular characterization of the concerned disease. This short commentary is mainly dedicated to these rationally-based success stories.

Hydrogen cyanide poisoning in a prison environment: a case report.

Cyanide poisoning is an important source of morbidity and mortality from smoke exposure in structural fires. This case involved administration of a cyanide antidote to a prisoner (male, 23 years) in France, discovered in cardiorespiratory arrest after about 30 minutes exposure to smoke from a burning mattress during an apparent suicide attempt. Smoke exposure, circulatory failure during initial resuscitation, and elevated blood cyanide and lactate led to the diagnosis of cyanide poisoning. Hydroxocobalamin (Cyanokit®), 5 g intravenous) was given immediately and on arrival at the hospital. Cardiopulmonary resuscitation restored cardiovascular function after 33 minutes. There were no neurological or other sequelae. Timely hydroxocobalamin administration contributed to full recovery from cardiorespiratory arrest secondary to cyanide poisoning from smoke inhalation. Hydroxocobalamin should be available to emergency medical teams attending fire scenes.