Combining the Power of Patient Advocacy, Cost-Effective Manufacturing to Bring Gene Therapies to Market

By Chris Anderson

August 30, 2023 | At CHI’s Bioprocessing Summit earlier this month, Rachel Salzman, founder of The Stop ALD Foundation and Global Head, Corporate Strategy at Armatus Bio, described the 20-year effort to develop and gain approval for a gene therapy to treat cerebral adrenal leukodystrophy (ALD), a monogenic neuro-metabolic disease caused by mutations in the ABCD1 gene. Salzman recounted personal experience involving her three nephews who were all afflicted with the disease in the early 2000s.

ALD, also known as Lorenzo’s Oil disease, is caused by mutations in the ABCD1 gene that prevent the body from breaking down very-long-chain fatty acids. Its symptoms include learning disabilities, cognitive deficits, loss of motor skills, seizures, and eventually leads to a vegetative state and death. While some ALD patients can be treated via hematopoietic stem cell transplantation, reach is limited—roughly 70% of patients don’t find a donor match. The need to develop a different form of therapy for children with ALD was pressing, so researchers shifted to a possible gene therapy to treat the disease.

But gene therapies, especially those treating rare genetic disorders, can be difficult to develop and bring through the regulatory process due to biopharma companies’ changing priorities and profit motive. Further, some early efforts to develop gene therapies for other conditions—including one known as “bubble boy disease”—showed initial promise but many patients later developed leukemia, which caused the FDA and other regulatory agencies around the world to quickly halt trials. As Salzman worked to shepherd a gene therapy for ALD to market, regulatory environment challenges prompted one company with a promising technology, Cell Genesis, to pivot to cancer drug development instead.

Patient advocacy groups often play pivotal roles in advancing a gene therapy and this was the case with the drug Skysona, developed by bluebird bio, which eventually gained approval for ALD. In the US, Salzman’s sister—whose sons had ALD—traveled to Washington to testify before the NIH’s Recombinant RNA Advisory Committee (RAC) to advocate for the kind of clinical research that might yield a gene therapy.

Salzman noted at the time that the RAC wasn’t a panel of regulators, but her sister made a poignant plea for them to consider pushing ahead with trials. “These are her words: ‘Gene therapy is simply another potentially promising avenue that should be explored, it should be given the same opportunities offered to experimental drugs, surgeries, and other therapeutic approaches. We do not expect a homerun, we just want every chance at that possible,’” Salzman recounted.

The journey continued but wasn’t straight. Skysona was approved in Europe and then withdrawn after a time due to commercial concerns—not issues related to safety or efficacy. Then, in 2022, the FDA approved the treatment, and March marked the first patient dosed with this potentially life-saving therapy.

Salzman noted that the urgency a patient advocacy group can bring to the process is vital. Their ability to help share information between multiple stakeholders including patients, patient families, researchers, biotechs, and regulatory agencies—and to bring them together—adds power to the process.