BlackfinBio Ltd, a UK-based clinical stage gene therapy company, has received clearance from the U.S. Food and Drug Administration (FDA) to initiate a Phase 1/2 clinical trial for BFB-101, a novel adeno-associated virus (AAV) gene therapy developed to treat children with Hereditary Spastic Paraplegia Type 47 (SPG47).
The trial will be conducted at Boston Children's Hospital in the United States, with patient recruitment expected to commence by the end of 2025. This development represents a significant milestone in addressing an ultra-rare neurological condition that currently has no effective treatments.
Understanding SPG47: A Rare Pediatric Neurological Disorder
SPG47 is a rare autosomal-recessive neurological disorder characterized by progressive lower-limb spasticity, developmental delays, and intellectual disability in children. The condition is caused by deleterious mutations in the AP4B1 gene, which plays a critical role in neurological development.
The disease typically manifests in early childhood, with affected children experiencing increasing difficulty with mobility and cognitive function as the condition progresses. Currently, management is limited to supportive care and symptomatic treatments, highlighting the urgent need for disease-modifying therapies.
BFB-101: A Precision Medicine Approach
BFB-101 represents a novel approach to treating SPG47 by addressing its underlying genetic cause. The therapy delivers a functional copy of the AP4B1 gene using an adeno-associated virus vector, with the goal of halting or potentially reversing disease progression.
"BFB-101 has been designed specifically to address the underlying genetic cause of SPG47 by delivering a functional copy of the AP4B1 gene, with the goal of halting or reversing disease progression," explained Peter Nolan, Founder and Chief Executive Officer of BlackfinBio Ltd. "Preclinical results with BFB-101 have demonstrated promising activity and safety."
The FDA has granted both orphan drug designation (ODD) and rare pediatric disease designation (RPDD) to BFB-101 for the treatment of SPG47, recognizing the significant unmet medical need in this patient population.
Clinical Trial Design and Administration Method
The Phase 1/2 clinical trial is designed as a single-center, open-label study that will evaluate BFB-101 in up to five children with AP4B1-associated SPG47. The primary objective is to assess the safety and efficacy of a single injection administered via intra-cisterna magna (ICM) delivery.
This specialized administration method involves injecting the therapy into the cerebrospinal fluid at the base of the brainstem near the spinal cord. According to the researchers, ICM administration allows for rapid and efficient delivery of therapeutic agents to the central nervous system, which is critical for addressing neurological conditions.
Secondary objectives of the trial will evaluate BFB-101's impact on motor function, development, and health-related quality of life in the treated children.
Expert Perspectives on the Trial
Dr. Darius Ebrahimi-Fakhari, M.D., Ph.D., from Boston Children's Hospital, who will serve as the Principal Investigator for the trial, emphasized the significance of this development: "We are proud to be leading this important clinical trial at Boston Children's Hospital, bringing forward a precision medicine approach for children affected by SPG47. As clinicians, we see firsthand the impact of this disorder and the urgency for effective treatments."
Professor Mimoun Azzouz, Founder and Chief Scientific Officer of BlackfinBio Ltd, who oversaw the therapy's development from the discovery stage, added: "Given the incredibly high unmet need for children with this devastating condition, we are on a mission at BlackfinBio to transform treatment options for these young lives and make a real impact to the lives of their families."
Development History and Collaborative Efforts
BFB-101 was originally developed by Professor Azzouz at the University of Sheffield with support from patient advocacy organization Cure AP-4 and the medical research charity LifeArc. The project also received partial funding from the Innovative Medicines Initiative 2 Joint Undertaking to support AAV9 capsid synthesis for immune response studies.
The therapy is administered as a single lifetime dose and has shown potential in restoring AP-4 function in laboratory studies. Preclinical research demonstrated improved motor function in AP4B1 mutant mice, providing the foundation for advancing to human clinical trials.
Looking Toward Future Impact
If successful, this clinical trial could provide the first effective treatment option for children with SPG47, potentially transforming the management of this devastating neurological condition. Beyond SPG47, the approach may also inform treatment strategies for related neurological disorders.
"The FDA's clearance of the BFB-101 IND is an important milestone for our rare neurological disease program and the company," said Nolan. "We look forward to initiating enrollment in the U.S. later this year and are working closely with the investigator team at Boston Children's Hospital to evaluate the therapeutic utility of this gene therapy in children with SPG47."
For families affected by this rare condition, the advancement of BFB-101 into clinical trials represents a significant step forward in addressing a previously untreatable genetic disorder, offering new hope for improved outcomes and quality of life.
