Optimizing Dosing and Regulatory Outcomes in Duchenne Muscular Dystrophy (DMD) Drug Development

Italfarmaco developed Givinostat, an HDAC inhibitor for Duchenne Muscular Dystrophy (DMD), a rare and progressive neuromuscular disease. Developing drugs in rare diseases poses significant challenges; the limited patient population made recruitment, trial design, and demonstrating clinical benefit difficult.​

Optimizing pediatric dosing while ensuring efficacy and safety required a model-informed approach due to ethical and logistical trial constraints.​

For its pivotal study in children over six, Italfarmaco adopted a pharmacometric approach as the most effective strategy given the context. Key challenges included a small patient population, sparse data, complex weight-based dosing, and regulatory concerns around dose effectiveness and safety for FDA and EMA submissions.​

A robust modeling strategy was essential to overcome these challenges and ensure regulatory success.

Certara provided essential pharmacometric and regulatory support to optimize submission strategy and facilitate agency interactions. ​

Key contributions included:​

• Pharmacometric Analysis: Conducted population PK, PK/PD, and exposure-response modeling to refine dosing.​
• Regulatory Strategy & Engagement: Supported FDA and EMA interactions to address regulatory challenges.​
• ​Data Programming & Quality Control: Integrated study data, ensuring analysis-ready datasets and quality submissions.​
• Adaptive Dosing Strategy Development: Redefined dosing regimens to optimize safety and therapeutic outcomes.

Certara’s Impact on DMD Drug Development: Pharmacometric Support for Givinostat’s FDA Approval as a Nonsteroidal Pediatric Treatment​

Key outcomes included:​

• Approval of a weight-based dosing regimen balancing efficacy and side effects.​
• Stronger regulatory engagement, shifting focus to exposure-response relationships for a successful submission.​
• Ongoing collaboration for new indications, including expansion to younger populations (ages 2-6).​
• Continued post-approval support, including safety monitoring and disease progression modeling.