FDA names stem cell therapy for FA, PPL-001, rare pediatric disease
Potential therapy uses gene editing approach to restore frataxin production
The U.S. Food and Drug Administration (FDA) has given rare pediatric disease designation to PPL-001, Papillon Therapeutics’ investigational cell therapy for Friedreich’s ataxia (FA).
This status is granted to potential medicines or therapy approaches meant to treat serious or life-threatening diseases affecting fewer than 200,000 people in the U.S., primarily children and adolescents younger than age 18. If the therapy goes on to be approved, its developer may qualify for a priority voucher that can be used for accelerated review of a different product, or be sold or transferred to another sponsor.
“We are thrilled to receive Rare Pediatric Disease designation for PPL-001 and appreciate the FDA’s ongoing support,” Carter Cliff, Papillon’s CEO, said in a company press release. “It marks an important milestone in our commitment to making a meaningful impact in the lives of patients and their families.”
PPL-001 aims to correct the disease’s underlying genetic defect in cells
FA is caused by defects in the FXN gene that disrupt the production of frataxin, a protein essential for the functioning of mitochondria — small cellular structures that produce energy. Most commonly, the genetic defect is the excessive expansion of a section in the FXN gene that contains three DNA building blocks, GAA (one guanine and two adenines).
Hallmark FA symptoms include problems in motor coordination and balance (ataxia), muscle weakness, heart abnormalities, and neurological issues.
In PPL-001, hematopoietic stem and progenitor cells (HSPCs) — immature cells in the bone marrow and blood that can give rise to several mature cell types, including blood and immune cells — are collected from a patient. Then, the GAA repeat expansion is corrected using the CRISPR-Cas9 gene editing technology, and the cells are infused back to the patient.
In CRISPR-Cas9, a small guide RNA molecule binds to a target DNA sequence. Then, the Cas9 enzyme cuts the DNA at the targeted location, and the cell’s machinery adds or deletes the genetic material.
The therapy is designed to restore frataxin production in various organs, including the heart, brain, and spinal cord, which is expected to slow or reverse disease progression.
In a preclinical study using patient-derived nerve cells, researchers demonstrated that the gene editing approach was able to restore frataxin production, as well as to prevent an increase in markers of cell death, mitochondrial dysfunction, and oxidative stress, a type of cell damage associated with the mitochondrial problems seen in patients.
PPL-001 recently received FDA orphan drug status, a designation meant to encourage treatment development for rare diseases. It comes with certain advantages, including tax credits toward the cost of clinical trials, and seven years of market exclusivity if the therapy ultimately is approved.
