Recently, an 11-year-old girl named Willow, who was born with the ultrarare disease arginase-1 deficiency (ARG1-D), found hope in a new therapy called pegzilarginase. This therapy has shown promise in reducing arginine levels, a key factor in the disease, and improving mobility for patients with ARG1-D. However, the FDA’s refusal to consider the trial data and insistence on large clinical trials has led to the denial of approval for this potentially life-changing drug.
ARG1-D is an exceptionally rare disease, affecting fewer than three in every million babies born. It causes severe intellectual disabilities, loss of bodily control, and reduced life expectancy. Until the development of pegzilarginase, the only treatment for ARG1-D was a highly restrictive low-protein diet, which offered limited relief.
In 2019, clinical trials for pegzilarginase showed promising results, with over 90% of patients experiencing a decrease in arginine levels and improved mobility. However, the FDA’s requirement for statistical significance in clinical benefit led to the refusal to file for approval, devastating patients and forcing the drug developer, Aeglea BioTherapeutics, to close its ARG1-D program.
In light of the FDA’s decision, Christine Zahn, founder and director of the Arginase 1 Deficiency Foundation and grandmother of a child with ARG1-D, has raised concerns about the agency’s evaluation of rare-disease drugs. She advocates for the consideration of biomarkers in evaluating drug effectiveness, pointing out that there is precedent for this approach with HIV and cancer drugs.
As a result of the FDA’s decision, patients like Willow have been left without access to a potential life-changing treatment. Zahn emphasizes the need for the FDA to reconsider its evaluation process and take into account the unique challenges of rare diseases when assessing potential therapies.
Historically, the FDA has faced criticism for its approval process for drugs to treat rare diseases. The rarity of these conditions makes it challenging to conduct large clinical trials, leading to delays in potentially life-saving treatments reaching those in need.
The heartbreaking story of Willow and other patients struggling with ultrarare diseases brings attention to the need for a reevaluation of how the FDA evaluates drugs for these conditions, and the importance of considering alternative approaches to clinical trials in order to bring hope to those who have few treatment options.
