FDA Flexibility Leads to First Approved Gene Therapy for Rare Blood & Immune System Disorder

A genetic disorder that leads to bleeding episodes and life-threatening infections has a new FDA approved treatment, a regulatory decision that marks two notable firsts — the first gene therapy for this rare disease, Wiskott-Aldrich syndrome, and the first cell and gene therapy approval awarded to a non-profit entity.

The FDA decision announced late Tuesday covers the treatment of children age six months and older who have the mutation driving Wiskott-Aldrich syndrome. These patients must also be eligible for a stem cell transplant but cannot get one because no matched donor is available. This gene therapy from Fondazione Telethon, known in development as etuvetidigene autotemcel (etu-cel for short), will be commercialized under the brand name Waskyra. The therapy is also making regulatory progress in Europe. Last month, the European Medicines Agency issued a positive opinion supporting marketing authorization for the one-time treatment.

Wiskott-Aldrich syndrome is caused by a mutation in the gene that provides instructions for making WAS protein. This protein, found in all blood cells and some immune cells, plays a key role in immune system organization and function. Patients who have the rare disease can experience episodes of excessive bleeding, frequent infections, and eczema. The WAS gene is located on the X chromosome, so Wiskott-Aldrich syndrome almost exclusively affects males. According to the Wiskott-Aldrich Foundation, the disease is found in about four of every 1 million live births; an estimated 500 patients are in the U.S.

Treatment of Wiskott-Aldrich syndrome has been mainly caring for and managing disease symptoms. A hematopoietic stem cell transplant can be curative, but this option requires a matched donor and is most effective when performed early in a patient’s life. The transplant procedure also comes with complication risks. Waskyra introduces a genetic fix for the disease’s underlying cause. The therapy is made by collecting a patient’s hematopoietic stem cells and, in a lab, engineering those cells to include functional copies of the WAS gene. Following a patient preconditioning regimen, the modified cells are infused into the body, where they are intended to restore expression of functional WAS protein in cells.

The regulatory submission for Waskyra was based on two open-label, single-arm clinical trials as well as an expanded access program that evaluated the gene therapy. In total, these studies spanned 27 patients ranging in age from 6 months to 16 years old. In some patients, the follow-up period was up to 13 years. The latest results were presented earlier this week during the annual meeting of the American Society of Hematology in Orlando, Florida.

The main goals of the clinical program were measuring overall survival, the rate of severe infections in the six to 18 months after dosing, and the rate of moderate-to-severe bleeding events in the first 12 months after dosing. Results show overall survival was 96%; one expanded access patient died 4.5 months after receiving treatment due to deterioration of a pre-existing neurological condition. The rate of severe infections in the six to 18 month post-treatment period was reduced by 93% compared to the 12 months period prior to treatment. Also, moderate and severe bleeding events were reduced by 60% in the 12 months post-treatment period compared to the 12 months before Waskyra was administered.

The gene therapy was well tolerated with no treatment-related adverse events reported. The most common side effects associated with Waskyra include rash, respiratory tract infection, and infections related to the catheter used to administer the gene therapy.

Though the FDA said Waskyra is the first approved cell and gene therapy product from a non-profit applicant, for-profit entities had opportunities with this program. Waskyra traces its roots to research at the San Raffaele Telethon Institute for Gene Therapy in Milan, Italy. GSK licensed rights to develop the gene therapy, but in 2018 transferred its rare disease gene therapy assets to Orchard Therapeutics.

Orchard advanced clinical development of Waskyra, but a 2022 corporate restructuring resulted in the discontinuation of some programs, including the one for Wiskott-Aldrich syndrome. In 2024, Fondazione Telethon acquired the therapy’s rights. This Rome-based nonprofit organization, which funds research in rare and complex genetic diseases, currently markets Strimvelis, a gene therapy approved for treating severe combined immunodeficiency due to adenosine deaminase deficiency. Strimvelis, which came from San Raffaele Telethon Institute for Gene Therapy research, won its FDA approval under Orchard.

“The FDA’s approval of Waskyra is an extraordinary achievement — not only for Italian research and for Fondazione Telethon, but for the global rare disease community,” Fondazione Telethon CEO Ilaria Villa said in a prepared statement. “It confirms the value of a patient-centered model that turns research into real treatments, especially where the market fails to act.”

The FDA said its review of Fondazione Telethon’s application “exercised appropriate regulatory flexibility.” This flexibility took into account considerations for the rare disease; clinical trial design; the mechanism of action of Waskyra; and the chemistry, manufacturing, and controls for the therapy, the agency said.

Waskyra’s approval comes with a rare pediatric disease priority review voucher, according to the product’s approval letter. These vouchers may be used to speed up regulatory review of another therapy for a rare pediatric disease. But voucher recipients may sell the regulatory fast pass, and many do to raise money for more R&D. Voucher purchase prices this year have topped $150 million.

Illustration: Ruslanas Baranauskas/Science Photo Library, via Getty Images