Advancing Research on Cellular and Gene Therapies

There’s renewed optimism in the biomedical research community that years of effort finally may begin to pay off for developing cutting-edge gene and cellular treatments for debilitating and life-threatening conditions. Researchers recently reported promising results from early clinical studies of new genetic treatments for serious eye disorders, and a “gene editing” technique is credited with treating serious leukemia in an infant.

To encourage these initiatives, FDA seeks to clarify policies for regulating cellular and tissue-based products. An FDA public meeting scheduled for April 26, 2016 will discuss key research strategies with the health care and research community. A main issue is whether premarket review and approval should be requried for products that are “minimally manipulated,” intended for homologous use only, are not combined with other cells or tissues, and meet certain standards for safety, as FDA has proposed in several guidances that map out terms for determining the status of such products. 

European regulators similarly are refining approaches for bringing to market more cellular and gene therapies and tissue-engineered products based on review by the Committee for Advanced Therapies under the EU’s centralised procedure, explained Tim Farris of ERA Consulting at the RAPS Regulatory Convergence conference in Baltimore. Farris noted that the European Union has authorized several cell and gene therapies since approval of Glybera in 2012. Additional “advanced therapy medicinal products” (ATMPs) are under review or expected to file applications, despite continual challenges in testing theses products in clinical trials.

Potential gene therapies for serious eye conditions are reporting positive results, as was recently announced by Spark Therapeutics from a pivotal trial of a new treatment for certain retinal dystrophies. Avalanche Biotechnologies similarly is developing a new platform for long-term protein delivery to the eye to treat age-related macular degeneration. Avalanche chief medical officer Samuel Barone explained at the RAPS conference that key challenges in testing gene therapies are whether to have a control group or to blind subjects, as such approaches may help assess safety and efficacy, but may increase risks for subjects. Selecting a trial population balanced between individuals with certain risks and those more likely to benefit also raises difficult issues, as severely affected subjects are often included in early-phase gene therapy trials, but may not be ideal due to an inability to tolerate invasive procedures and the likelihood of confounding adverse events.

Bettina Ziegele, head of the innovation office at the Paul-Ehrlich Institut (PEI) in Germany, described a “step-wise approach” for researchers to obtain scientific advice from PEI in developing somatic cell therapies, tissue-engineered products and gene therapies. She advised sponsors at the RAPS conference to avoid “bottlenecks” to product development that could arise from inadequate focus on viral safety and product quality issues, as well as in the design of clinical trials and statistical analysis.

A serious impediment to making innovative gene therapies available to patients is the high cost of extracting target cells from an individual, sending them to a manufacturing facility for alteration, and reinjecting them into the patient. The potential $1 million cost of such procedures is prompting biopharma companies to explore new payment strategies based on potential long-term health care savings from one-time treatments able to achieve cures of debilitating and lethal conditions.