Cell and gene therapy answers: Overcoming challenges for rare disease in pediatrics

17 November 2023

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

Building on the topic of rare diseases in our earlier blog, Labcorp cell and gene therapy leadership shared their insights on strategies for overcoming key challenges in rare disease studies in pediatric populations along with their predicted advancements in the field that may make meaningful changes for patients.

There are many challenges related to cell and gene therapy for rare and pediatric diseases. What strategies do you recommend for some of these challenges?

Running long-term follow up studies: Gene therapy studies are currently conducted at a few highly specialized centers, so patients and families often travel long distances, sometimes crossing borders, to these centers. As these studies have regulatory long-term follow up requirements, some of them up to 15 years, long-distance travel represents one of the major challenges. Sponsors should consider involving care providers close to the patient’s home, if possible, and explore the possibility of patient-centric sampling, such as devices that allow patients to perform blood sampling in their own home. Local data collection and other decentralized clinical trial practices will help reduce the burden for patients and ensure the collection of long-term follow-up data.

Addressing a lack of data: With a lack of epidemiological data as well as natural history data describing the disease course of “new” rare diseases which were only very recently described, researchers should consider prospective natural history studies in early clinical development to inform study design and seek regulatory advice early in the process.

Meeting regulatory requirements: Since pediatric studies can also be a first in human study, there is a need for robust preclinical data, as well as early involvement with regulators, KOLs and patient organizations to ensure the intended study design, study size and the outcome measures will meet regulatory requirements but also to ensure that the trial is feasible and meaningful to affected patients.

Conducting studies spanning wide age ranges: Facing limited sample volumes from young pediatric patients, we recommend whenever possible using standard of care sampling and working with pediatric-specific assays that only need minimal sample volumes, especially when starting a study with neonates and infants. It is important to note that different age groups can also require different assessments, especially as a pediatric study population mature and eventually even reach adulthood during the study. Sponsors should therefore also consider how the assessments will potentially change during a long-term follow up study.

Managing patient recruitment and retention: Study protocols often have very narrow windows for enrollment, during which all study requirements and expectations need to be addressed and discussed with the patient’s family, which is often struggling at the same time to manage a severe diagnosis. Parents/caregivers may only have limited knowledge about gene therapies, so education is important to strengthen the family’s commitment to the study and better support the family, as each family will have its own unique needs.

Creating a market access strategy: We suggest that a market access strategy should be developed early in the clinical development program to support competitive differentiation of products. Long-term follow up often focuses on adverse events that may occur over time, which is relevant to the cost-benefit analysis of treatment. 

What advancements do you expect to see in the next three to five years that could meaningfully impact the development of cell and gene therapies specific to rare and pediatric diseases?

We believe that extended newborn screening and improved diagnostic tools will enable rare disease diagnoses earlier in life, increasingly in very young children, and even fetuses. This will lead to increasing development of potential treatments for these diagnoses, which currently lack any curative treatments.

Previous gene therapy studies in children with progressive neurologic diseases have shown that early treatment leads to better outcomes. While it may not be possible to reverse existing damage, gene therapy has the clear potential to limit future damage. Consequently, our industry will see more highly complex gene therapy trials involving very young pediatric patients, as well as fetal gene therapy to correct genetic defects during pregnancy.

The next three to five years may also witness the development of enzyme replacement therapies that do cross the blood-brain barrier. Improved vectors may lead to repeat treatments; as of today, gene therapy is a one-time treatment. In addition, improved vectors might also reach the target tissue more easily, which would improve the safety profile of the products while also reducing the need for invasive product administration procedures. The latter would be particularly beneficial when it comes to pediatric patients as drug developers work to incorporate more patient-centric practices into their programs.

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

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