The potential and benefits of repurposing existing drugs to treat rare muscular dystrophies

ABSTRACT

Introduction: Muscular dystrophies encompass a heterogeneous group of rare genetic neuromuscular disorders affecting locomotor, cardiac and respiratory muscles. These diseases are mostly debilitating progressive disorders with poor prognosis. Despite the discovery of the genetic causes and in depth understanding of the pathophysiological changes that take place in these disorders, efficacious therapies are still to be developed. The expected price of innovative therapies that are reaching the market for such rare disorders are of concern.

Areas covered: For this review, Duchenne muscular dystrophy is used as an example of these disorders. Clinical features, pathophysiological processes, socioeconomic impact, investigational and recently marketed therapeutic modalities for this disease and their price tag are discussed. Tools to circumvent cost and time for therapeutic development for such disorders are described highlighting the potential of this pathway and the obstacles to overcome.

Expert opinion: Repurposing already existing drugs with a well-studied pharmacokinetic, pharmacodynamic and safety profile holds a tremendous promise in delivering efficacious therapies in a cost controlled and timely manner to patients suffering life-threatening diseases who cannot wait for a classical drug development cycle. The use of this path is accelerated by incentives, guidance and protection provided by holding an orphan drug designation status.

KEYWORDS:

• Duchenne muscular dystrophy
• socioeconomic impact
• drug price
• drug repurposing
• orphan drug designation

Article highlights

• Duchenne muscular dystrophy is a progressive rare genetic myopathy affecting 1 in 3500 male birth with a poor prognosis and with no cure to date

• The socioeconomic burden of DMD is quite high justifying the need for the quick development of efficacious therapies

• Despite the plethora of investigational therapies in preclinical development, very few compounds reach clinical testing and even less are approved

• Price tags of the approved therapies despite the justification limit massively patients access and appear to be unsustainable to both patients and the healthcare systems

• Two available strategies to circumvent both cost and time needed to develop an efficacious therapy are discussed; repurposing existing drugs and orphan drug designations

This box summarizes key points contained in the article.

Acknowledgments

The authors would like to thank Professor Urs T. Ruegg for his assistance in proof reading this manuscript.

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. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

HM Ismail is supported by grants from the Fondation Suisse de Recherche sur les Maladies Musculaires (FSRMM). OM Dorchies is supported by grants from the Fondation Suisse de Recherche sur les Maladies Musculaires (FSRMM), Association Française contre les Myopathies (AFM-Telethon) and Duchenne UK. L Scaopzza is supported by grants from Swiss National Science Foundation (SNSF), the Fondation Suisse de Recherche sur les Maladies Musculaires (FSRMM), the Association Française contre les Myopathies (AFM-Telethon), and Duchenne UK.