Targeting shared molecular etiologies to accelerate drug development for rare diseases

Area of Science:

• Genetics and Genomics
• Clinical Pharmacology
• Translational Medicine

Background:

• Rare diseases impact over 400 million globally, with fewer than 5% having approved treatments.
• Many rare diseases share common, therapeutically actionable molecular etiologies.
• Traditional symptom-based disease classification limits clinical trial enrollment and therapeutic development.

Purpose of the Study:

• To propose grouping rare disease patients by molecular etiology for clinical trials.
• To highlight the potential of basket clinical trials to accelerate rare disease therapy development.
• To advocate for the adoption of molecular etiology-based trials by stakeholders.

Main Methods:

• Reviewing the success of basket trials in oncology.
• Analyzing the shared molecular etiologies across various rare diseases.
• Assessing the feasibility and benefits of implementing basket trials in rare diseases.

Main Results:

• Shared molecular etiologies offer a viable strategy for grouping diverse rare diseases.
• Basket trials, proven in oncology, can be adapted for rare diseases.
• This approach has broad stakeholder support for advancing rare disease treatments.

Conclusions:

• Basket clinical trials based on molecular etiology can significantly increase patient access to novel therapies.
• This innovative trial design accelerates the identification of treatments for rare diseases.
• Implementing this strategy addresses critical unmet medical needs in the rare disease community.