FDA Commissioner Defends Approval Standards Amidst Trial Failures

Key Insights

• FDA Commissioner Robert Califf addressed concerns that the agency is lowering its standards for drug approvals, even when clinical trials fail to meet endpoints.
• The FDA's decision to expand Sarepta Therapeutics' Elevidys approval for Duchenne muscular dystrophy, despite a failed Phase 3 trial, has drawn criticism.
• Travere Therapeutics' Filspari, a drug for IgAN, also received full approval despite failing its Phase 3 confirmatory trial, sparking debate about biomarker-based approvals.

At a recent event, FDA Commissioner Robert Califf responded to criticism that the agency is relaxing its approval standards for new drugs, particularly in cases where clinical trials have failed to achieve their primary endpoints. This comes after the FDA's controversial decisions regarding Sarepta Therapeutics' Elevidys and Travere Therapeutics' Filspari.

Elevidys Approval Controversy

The FDA's decision to expand the accelerated approval of Sarepta Therapeutics' Elevidys, a gene therapy for Duchenne muscular dystrophy (DMD), has faced scrutiny. This decision was made despite the drug failing to meet its endpoints in a Phase 3 trial. Former FDA chief scientist Luciana Borio criticized the move, calling it a "mockery of scientific reasoning and approval standards."

Elevidys is designed to deliver a functional dystrophin gene to muscle cells in patients with DMD, a rare and progressive muscle-wasting disease. The initial accelerated approval was based on surrogate endpoints, specifically the expression of the dystrophin protein. However, the Phase 3 trial results raised questions about the therapy's clinical benefit.

Filspari's Full Approval

Another point of contention is the full approval granted to Travere Therapeutics' Filspari for IgA nephropathy (IgAN), a rare autoimmune kidney disease. The approval was converted from an accelerated approval, which was based on biomarker outcomes. However, the confirmatory Phase 3 trial did not meet its final endpoints.

Filspari is a dual endothelin angiotensin receptor antagonist. It aims to reduce proteinuria, a key marker of kidney damage in IgAN patients. While the drug demonstrated a reduction in proteinuria, the long-term clinical benefits remain under investigation.

Justifying the Decisions

Commissioner Califf defended the agency's decisions, emphasizing the need to balance regulatory rigor with the urgency of providing treatments for serious and life-threatening diseases. He argued that the FDA carefully considers all available data, including biomarker data and clinical trial results, when making approval decisions. The accelerated approval pathway allows for earlier access to potentially beneficial therapies while requiring post-market studies to confirm clinical benefit.