Targeting shared molecular etiologies to accelerate drug development for rare diseases

EMBO Mol Med. 2023 Jul 10;15(7):e17159. doi: 10.15252/emmm.202217159. Epub 2023 Jun 27.

Abstract

Rare diseases affect over 400 million people worldwide and less than 5% of rare diseases have an approved treatment. Fortunately, the number of underlying disease etiologies is far less than the number of diseases, because many rare diseases share a common molecular etiology. Moreover, many of these shared molecular etiologies are therapeutically actionable. Grouping rare disease patients for clinical trials based on the underlying molecular etiology, rather than the traditional, symptom-based definition of disease, has the potential to greatly increase the number of patients gaining access to clinical trials. Basket clinical trials based on a shared molecular drug target have become common in the field of oncology and have been accepted by regulatory agencies as a basis for drug approvals. Implementation of basket clinical trials in the field of rare diseases is seen by multiple stakeholders-patients, researchers, clinicians, industry, regulators, and funders-as a solution to accelerate the identification of new therapies and address patient's unmet needs.

Keywords: IRDiRC; basket clinical trials; rare diseases; shared molecular etiologies; therapeutic development.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Drug Approval*
  • Humans
  • Rare Diseases* / drug therapy