Future perspectives for cryptococcosis treatment

ABSTRACT

Introduction: Cryptococcosis is one of the most devastating human fungal infections. Despite its impact, none of the standard antifungals were developed after 1990. New, improved, less toxic, affordable and widely available treatment is, therefore, imperative.

Areas covered: This review offers an insight into technological developments for cryptococcosis disclosed in patent literature. From a broad search of patent documents claiming cryptococcosis treatment and having earliest priority between 1995 and 2015, we selected and summarized compounds/molecules (i) revealed in documents disclosing in vivo activity against Cryptococcus spp. or (ii) found in the pipeline of companies that appeared as assignees in our patent search. This information was complemented with data on compounds under development for this indication from the database Integrity (Clarivate Analytics).

Expert opinion: This review demonstrates that drug development against cryptococcosis is discrete. However, it also shows that the existing development is not focused on a single class of molecules, but on different types of molecules with distinct fungal targets, reflecting the complexity of generating novel anti-cryptococcal tools. Given the intrinsic difficulties and high costs of drug development and the evident market failure in this field, we consider drug repurposing the most promising avenue for cryptococcosis treatment.

KEYWORDS:

• Antifungals
• cryptococcosis
• cryptococcus
• patent landscape

Article highlights

• This review article covers technological developments for cryptococcosis treatment disclosed in patent documents.

• Cryptococcosis is not the main focus of most of these documents and experimental evidence disclosed against Cryptococcus spp. is very preliminary, mostly consisting in minimum inhibition assays.

• To make an estimate of most promising inventions, we (i) selected and summarized patents containing evidence of in vivo activity against Cryptococcus spp., (ii) analyzed the pipeline of companies indicated as assignees in all patent documents recovered to identify compounds/molecules currently under development, and (iii) complemented this information with data from the database Integrity.

• A total of 22 compounds/molecules were identified by our strategy.

• Given the market failure for cryptococcosis treatment we consider that repurposing would be the most promising strategy to meet the current clinical needs.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This manuscript was funded by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)/Ministério da Ciência, Tecnologia, Inovações e Comunicações, Ministério da Educação/Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ) (465313/2014-0) and Fundação Oswaldo Cruz (Fiocruz).