The Galien Forum USA 2018

The Promise of Gene Therapy


Ever since the achievement of sequencing the human genome, scientists have had the unprecedented opportunity to characterize and understand rare diseases caused by a single faulty gene. As a result, breakthrough approaches to addressing those diseases are emerging with high frequency. This revolution in discovery science has become evident in the past year, with the FDA approval of Luxturna (voretigene neparvovvec-rzyl), the first single-gene replacement therapy for a rare progressive form of blindness. This milestone is a radical step forward into a landscape that scientists, regulators and industry regard as the next frontier in scientific innovation.

Gene therapy is considered to be so innovative because of its potential to provide cures to certain patients who in many cases have seen only palliative treatments. One key way approach is to use viruses and their DNA-delivery capabilities to deliver an additional extra-chromosomal gene copy to specific tissues. The adeno-associated viral vector (AAV) is a common tool being explored in a broad range of conditions, and is already in clinical trials for rare diseases including Hemophilia A and B, Spinal muscular atropy (SMA), and Duchenne muscular dystrophy (DMD). Another growing area looks at the use of lentiviruses, a viral vector with the ability to integrate into non-dividing cells, as pursued by Bluebird Bio for the treatment of the blood diseases Sickle cell disease and beta-thalassemia, as well as the rare metabolic disease cerebral ALD.

The scientific progress occurring in the gene therapy space has been facilitated by a supportive external environment—and that environment is itself innovative. The research that has led to gene therapy advances has often taken the form of partnerships between pharma companies, biotechs, and academia. And gene therapy has also received a boost from a more favorable regulatory climate, as agencies have been receptive to harmonizing clinical research, approvals, and marketing processes. As an example, a collaboration between Pfizer and SPARK Therapeutics enabled the acceleration of a gene therapy candidate for Hemophilia B, which generated positive results in a Phase 1/2 study earlier this year and is now being evaluated in a Phase 3 lead-in trial.

However, some caution about the pace of progress is necessary. Besides challenges in the science itself, there are a host of complex commercial issues that each company must address separately, including IP rights to novel human biologic components; certification and set-up of clinical affiliations to administer treatments and monitor side-effects; manufacturing, which requires the resolution of sensitive logistical issues; and payment and reimbursement. How this will ultimately be resolved in a way that enables full access to the eligible patient population is unknown, and is at odds with the predictability demanded by investors.

The following group of experts, chaired by Pfizer President of Worldwide Research and Development Mikael Dolsten, and representing the discovery academic community, regulators and the innovative industry, will address these issues in detail, with particular emphasis on how to ensure business and society’s expectations continue to keep pace with the rapid progression of science.