Advancements in Gene Therapy for ADA-SCID: A Collaborative Effort by UCLA and UCL

Researchers from the University of California, Los Angeles (UCLA) and University College London (UCL) are advancing a gene therapy known as EFS-ADA LV, aimed at treating severe combined immunodeficiency due to adenosine deaminase deficiency (ADA-SCID). This rare genetic disorder leads to a lack of functional immune cells, resulting in severe vulnerability to infections. The therapy involves modifying a patient's own hematopoietic stem cells to produce healthy immune cells, with the goal of providing a sustainable cure.

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The teams at UCLA and UCL are preparing to seek regulatory approvals from the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare Products Regulatory Agency (MHRA), respectively. Donald Kohn, a professor at UCLA, emphasized the need for commercialization, stating, "It's no longer a research question." The researchers aim to develop a commercial-grade manufacturing process to make the treatment widely available, supported by a grant from the California Institute for Regenerative Medicine (CIRM).

UCLA, University College London Researchers Push to Commercialize ADA-SCID Gene Therapy

Initially, components of the gene therapy were licensed to Orchard Therapeutics in 2016. However, Orchard dropped the program in 2022 due to financial constraints and returned the license to UCLA. Subsequently, UCLA licensed the therapy to Rarity PBC, a company co-founded by Kohn, to manage clinical and regulatory operations. Orchard Therapeutics acknowledged investing over $60 million before deciding to deprioritize the program, citing difficulties in creating a commercial-grade manufacturing process.

UCLA, University College London Researchers Push to Commercialize ADA-SCID Gene Therapy

The gene therapy has shown promising results in clinical trials, with a Phase I/II trial demonstrating long-term efficacy and safety. Out of 62 patients treated, 59 achieved restored immune function, allowing them to live without additional therapies. The median follow-up time was 7.5 years, with no reported deaths among the patients. Claire Booth, a professor at UCL, noted, "We've achieved a lasting therapeutic response without any safety concerns, effectively providing a cure."

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Despite the positive outcomes, researchers acknowledge challenges in commercial viability due to the small patient population and high manufacturing costs. Booth and Kohn have indicated that they are exploring alternative pathways to ensure the therapy reaches patients. The limited market for ADA-SCID treatments complicates efforts to recoup development costs, as highlighted in their published findings.

UCLA, University College London Researchers Push to Commercialize ADA-SCID Gene Therapy

The next steps involve gathering evidence on the commercial manufacturing process and filing a biologics license application (BLA) with the FDA. If approved, this therapy could significantly improve treatment options for ADA-SCID patients, who currently face risks associated with standard care methods. The researchers are optimistic about the potential impact of EFS-ADA LV on the treatment landscape for rare genetic disorders.

UCLA, University College London Researchers Push to Commercialize ADA-SCID Gene Therapy

• “It's no longer a research question,” — Donald Kohn, Professor, UCLA

UCLA, University College London Researchers Push to Commercialize ADA-SCID Gene Therapy

• “We've achieved a lasting therapeutic response without any safety concerns, effectively providing a cure,” — Claire Booth, Professor, UCL

UCLA, University College London Researchers Push to Commercialize ADA-SCID Gene Therapy

• “The long-term follow-up data we've published really confirm that this therapy works safely over time, which is key to making it available for patients who need it,” — Claire Booth, Professor, UCL

UCLA, University College London Researchers Push to Commercialize ADA-SCID Gene Therapy

This collaborative effort between UCLA and UCL represents a significant step forward in gene therapy for ADA-SCID, with the potential to change the lives of affected patients.

UCLA, University College London Researchers Push to Commercialize ADA-SCID Gene Therapy