In a significant move that could reshape the treatment landscape for schizophrenia, a joint meeting of the FDA's Drug Safety and Risk Management Advisory Committee and the Psychopharmacologic Drugs Advisory Committee voted overwhelmingly to dismiss the clozapine Risk Evaluation and Mitigation Strategy (REMS). The committees concluded that the REMS protocol, which mandates monitoring, documenting, and verifying absolute neutrophil count (ANC) results, is no longer necessary and may impede patient access to this critical medication. The vote was 14 to 1 in favor of dismissal.
The decision came after a hearing featuring testimony from leading experts in the field. Dr. John Kane from the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, emphasized clozapine's role as a "cornerstone in the treatment of schizophrenia," citing its impact on treatment-resistant cases, improved functioning, reduced mortality, and decreased relapse risk. He noted that the US lags behind other countries in clozapine utilization, partly due to the REMS-related delays.
Dr. Kane addressed the primary concern behind the REMS – clozapine-induced neutropenia. He explained that the most severe cases typically occur within the first 18 weeks of treatment, with the risk diminishing substantially after two years. "Long-term risk excess is small compared with advantages of clozapine in outcomes, including life expectancy," he stated, suggesting that relaxing long-term monitoring could enhance clozapine's benefits without significantly increasing neutropenia risk.
Dr. Robert O. Cotes from Emory University School of Medicine, highlighted the challenges faced by prescribers, patients, and caregivers due to the REMS requirements. A study he cited revealed that 60% of clinicians prescribing clozapine reported that the safe use requirements often delayed patients from receiving the medication. He further explained that interruptions in treatment caused by REMS-related bureaucracy can necessitate re-titration, cause psychological distress, physical discomfort, symptom exacerbation, and even hospitalization.
Kathryn K. Erickson-Ridout, MD, representing the American Psychiatric Association's Council on Quality Care, testified that the REMS program, despite its good intentions, creates a barrier to both prescribers and patients. She shared her experience of witnessing the "life-transforming benefit" of clozapine in controlling treatment-resistant psychotic symptoms and improving cognitive clarity. She also emphasized that disruptions in care resulting from the REMS protocol can lead to "disastrous results."
Sascha Dublin, MD, PhD, an epidemiologist and panelist, supported the need for monitoring and support but cautioned against a "punitive and technocratic approach." She stated, "I do not believe that the REMS' approach to documenting and enforcing is serving the health of the patients or the needs of the community."
While the committee largely agreed on dismissing the REMS, Dr. Walter Dunn from UCLA David Geffen School of Medicine, expressed a preference for continued monitoring during the initial 18 weeks of treatment when the risk is highest. However, he suggested a more streamlined program without ANC levels.
The potential elimination of the clozapine REMS is seen as a significant step toward improving access to a critical medication for individuals with treatment-resistant schizophrenia. The decision reflects a growing recognition that the burdens imposed by the REMS protocol may outweigh its benefits, hindering timely treatment and negatively impacting patient outcomes.
