Cell and Gene Therapy Answers: Advancing treatments for pediatric patients with rare diseases

16 November 2023

Your source for answers to the complex challenges of cell and gene therapy development.

Labcorp’s cell and gene therapy scientific leaders shared their insights on the factors that make rare and pediatric diseases a good fit for cell and gene therapy, along with the key challenges and best practices in this innovative space.

Tell us about the current landscape of cell and gene therapy development for rare diseases in pediatrics.

Research in this area has accelerated over the last ten years, along with technological improvements, resulting in several approvals for gene and cell therapies in a broad variety of indications. Oncology remains the most active therapeutic area overall, with over 1,200 therapies in development at the end of the first quarter of 2021. Neurological disease is the most common non-oncologic disease area targeted by gene therapy (with 35 different therapies currently in development), followed by ocular disease. Globally, as of April 2021, 16 different gene therapies have been approved, including genetically modified cell therapies, and 53 non-genetically modified cell therapies have been approved. 

Here at Labcorp, our oncology is oriented to cell therapy, with CAR-Ts being the prime example. In rare diseases, our work mostly involves AAV-based gene therapies in the ophthalmologic, neuro and hematologic indications. We are seeing an upward trend in cell therapies in rare diseases. We are excited to see cell and gene therapies move into non-rare indications, such as for various forms of arthritis and cardiovascular disease.

What is unique about rare diseases in pediatrics that makes these diseases a good fit for cell and/or gene therapy?

Most of the 7,000 or so pediatric rare diseases are monogenic disorders, which are inherited conditions from mutations involving a single gene. About half of these diseases manifest during childhood, and many can lead to significant morbidity and even premature death. At the same time, treatment for these diseases remains insufficient. Care is primarily focused on disease management, without addressing the underlying genetic defects. Due to these factors, rare diseases are prime candidates for implementation of cell and gene therapies in pediatric (and adult) patients.

What are key considerations for clients developing cell or gene therapies, specifically for rare diseases in pediatrics?

Supporting the development of cell and gene therapy (CGT) is similar to rare disease drug development. We face small populations of patients (often made smaller because of CGT eligibility criteria). These populations may be geographically spread out, with no placebo control, and patients and their families may require significant support to participate in a clinical study.

The results of a recent simulation suggest that more than one million patients are expected to be treated by gene therapy in the US between January 2020 and December 2034. It is estimated that at least one third of these therapies will treat children. The FDA has already approved the gene therapies Luxturna for Leber’s Congenital Amaurosis (LCA) and Zolgensma for Spinal Muscular Atrophy (SMA).

For hemophilia, the rare, X-linked hereditary bleeding disorder caused by defects/mutations in the F8 or F9 gene, gene therapy has proven to provide a suitable treatment given that the disease is caused by a single gene defect. Minimal expression of the coagulation factors already leads to major improvement of the bleeding phenotype and gene expression can be evaluated easily by measuring factor levels in plasma.

In 2006, the first AAV2-based liver-directed gene therapy clinical study in patients with hemophilia B showed temporary expression of Factor IX. Long-term follow up revealed no adverse events, no liver toxicity, and no development of hepatocellular carcinoma (HCC), even after a period of 12 to 15 years after vector administration.

In 2011, patients with hemophilia B were treated with intravenously administered liver-directed AAV8-based therapy, which resulted in a reduction of bleedings without the need for further prophylaxis. After three years, patients treated with the highest vector dose showed long-term stable expression, even lasting for up to eight years. These promising results were the basis for further gene therapy development, with 47 gene therapy hemophilia trials currently ongoing; however, clinical studies have not moved into pediatric populations so far.

Despite these successes, several open questions remain, which warrant further research and long-term follow up. Pediatric studies might be a first in human study if the disease doesn’t exist in adults. At the moment, gene therapy is a one-time treatment, and repeat dosing is not possible, due to the development of neutralizing antibodies to the vector.

Further, these trials are currently conducted at a few highly specialized centers; they are highly complex, often invasive and may require pretreatment with immunosuppression. Long-distance and even cross-border travel may be necessary. Study visits can be lengthy, with multiple assessments during visits, and the possibility of long hospital stays both during and post-treatment. Long-term follow up and data collection are also key challenges in this space.

Read more about addressing challenges in rare and pediatric diseases in part two of this blog

Learn how we can support your needs to advance your cell and gene therapies by visiting our website.

Hear from our experts in our CGTAnswers blog series on additional topics: ddPCRCMConcology and Cell & Gene Therapy