Expert Review on Practical Considerations for the Use of Givinostat in Clinical Practice

Topic:

Clinical Management

Poster Number: 17 S

Author(s):

Aravindhan Veerapandiyan, MD, Arkansas Children’s Hospital, University of Arkansas for Medical Sciences, Little Rock, Arkansas, US, Kaitlin Batley, MD, Children's Health/UT Southwestern, John Brandsema, MD, Children's Hospital of Philadelphia, Diana Castro, MD, Neurology Rare Disease Center, Denton, Texas, USA, Erika Finanger, MD, Oregon Health & Science University, Natalie Katz, MD, PhD, Duke University Medical Centre, Katherine Mathews, MD, University of Iowa, Iowa City, Iowa, USA, Crystal Proud, MD, Children’s Hospital of the King’s Daughters, Norfolk, VA, USA, Cuixia Tian, MD, Cincinnati Children’s Hospital Medical Center, Chet Villa, MD, Cincinnati Children’s Hospital Medical Center, Brenda Wong, MD, Duchenne Muscular Dystrophy Program, UMass Chan Medical School

Background: Givinostat, a histone deacetylase inhibitor, is approved in the U.S. for patients with Duchenne muscular dystrophy (DMD) aged six and older. In the pivotal Phase 3 EPIDYS study, thrombocytopenia, gastrointestinal (GI) events, and hypertriglyceridemia were the most common adverse events reported in patients receiving givinostat compared to placebo. In addition, specific monitoring steps regarding QTc interval prolongation were included in the trial and are also described in the labeling. While the USPI recommends monitoring protocols and dose adjustments, real-world practice shows variability in how these guidelines are implemented. For U.S. patients, several factors influence monitoring and management decisions, including proximity to clinic and laboratories, ambulatory status, cardiac health profile, and access to care resources.

Objective: To address these challenges, a panel of neuromuscular specialists convened to synthesize practical considerations and monitoring strategies for use of givinostat post-FDA approval in the U.S.

Methods: Drawing from both clinical trial data and clinical experience, the panel outlined actionable monitoring and dose-adjustment recommendations in response to key adverse events, specifically: thrombocytopenia, QTc prolongation, elevated triglycerides, and GI issues.

Results: In summary, upon dose reduction due to confirmed thrombocytopenia with platelet counts below 150,000×10⁹/L, the recommendation is that patients should be monitored bi-weekly for up to eight weeks without further dose adjustments to allow time for platelet recovery. However, platelets <75,000×10⁹/L would prompt reassessment or discontinuation; for QTc prolongation, a baseline ECG should be obtained before starting givinostat and repeated 1-2 weeks later, with ongoing monitoring that adheres to standard cardiac care practices and is tailored to each patient’s clinical situation; for hypertriglyceridemia, triglyceride levels should be regularly monitored as indicated in the USPI, with dose reduction or discontinuation considered if triglycerides persistently exceed 300 mg/dL despite interventions; in response to GI events, adjustments or interventions should be individualized based on symptom severity, ambulatory status, lifestyle, and patient support needs.

Conclusion: These practical considerations aim to maximize patient safety and tolerability.