A Rocket Pharmaceuticals gene therapy has landed a long-awaited FDA approval, bringing a new treatment option to patients with a certain inherited immunodeficiency so severe that many babies do not live beyond infancy.
The ultra-rare disease is called leukocyte-adhesion deficiency type 1, or LAD-I. It’s caused by mutations in the ITGB2 gene that lead to low levels of CD18, a protein that leukocytes need to adhere to the blood vessel wall and migrate to tissues. That capability is important for confining and clearing infections and sparking wound repair. LAD-I leads recurrent bacterial and fungal infections that respond poorly to antimicrobial drugs and require frequent hospitalizations.
One treatment option for LAD-I is a hematopoietic stem cell transplant, which requires a matched donor, typically a sibling. Even if a donor is available, the procedure comes with complication risks. Rocket’s gene therapy, marnetegragene autotemcel (brand name Kresladi), is made by harvesting a patient’s blood stem cells and engineering them in a lab to introduce functional copies of the ITGB2 gene.
Following a conditioning regimen to prepare the patient to receive the gene therapy, those modified cells are administered by intravenous infusion. This one-time treatment is intended to restore expression of CD18 and CD11a on the surface of white blood cells.
Rocket evaluated Kresladi in an open-label Phase 1/2 study that enrolled nine children age three months and older. The main goal was to measure CD18 and CD11a cell surface expression at one year. Results showed an increase in these measures at the one-year mark, an effect was sustained through two years. The most common side effects reported included anemia, low platelet and white blood cell counts, mouth sores, and upper respiratory tract infections. Preliminary results reported in 2022 showed 100% survival in clinical trial participants.
Rocket submitted an application seeking regulatory approval in 2023, but the FDA turned down the application the following year due to manufacturing issues. The agency did not raise questions about efficacy of the therapy or ask for another clinical trial. The study’s result showing an increase neutrophil CD18 and CD11a surface expression was a surrogate endpoint; the Friday regulatory decision is an accelerated approval. Confirmation of the therapy’s benefit will be based on longer-term follow-up data of treated patients in the ongoing clinical study and through a post-marketing registry.
“As a clinician, I have seen firsthand the serious impact that severe LAD-I can have on young children and their families,” Donald Kohn, professor of microbiology, immunology & molecular genetics at UCLA and the principal investigator in the Phase 1/2 study, said in a prepared statement. “The approval of Kresladi represents the culmination of many years of scientific research and clinical collaboration aimed at addressing the underlying cause of this devastating disease.”
FDA approval of Kresladi came with a rare pediatric disease priority review voucher, which Rocket may use to cut the review time of another rare disease therapy. Many companies opt to sell these vouchers, and Rocket said it will evaluate its options for the voucher “to enhance financial flexibility and maximize shareholder value.” Rocket reported having a $188.9 million cash position at the end of 2025, which it estimated would last through the second quarter of 2027.
In a research note, Leerink Partners analyst Mani Foroohar said the small market for LAD-I means Kresladi won’t be a significant revenue driver for the company. But selling the priority review voucher would provide a source of non-dilutive capital. Nevertheless, he said approval of the LAD-I gene therapy, Rocket’s first commercial product, offers positive readthrough to the rest of the pipeline.
From a stock standpoint, Foroohar said Rocket’s most significant pipeline asset is RP-A501, a gene therapy in development for Danon disease. This rare inherited lysosomal storage disorder leads to the buildup of toxic substances in cells, causing problems in skeletal and cardiac muscles. There are no FDA-approved therapies for Danon disease.
Last May, a patient fatality led the FDA to place a clinical hold on a Phase 2 test of RP-A501. A subsequent investigation found the death was likely due to a drug used in the pretreatment regimen for the gene therapy. Last August, the FDA cleared Rocket to resume clinical testing with a lower range of doses to balance safety and efficacy. In its annual report, Rocket said six Danon patients have been treated with RP-A501 to date.
Photo: Wong Yu Liang, Getty Images
