The Galien Forum USA 2019

Delivering on the patient promise of gene therapy


Ever since the achievement of sequencing the human genome, medical research has 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 and therapeutics has become evident in the past few years, with the FDA approval of multiple products, including Strimvelis, Luxturna (voretigene neparvovec-rzyl), Zolgensma, and Zynteglo. The approval of these products, and the large number of cell and gene therapy INDs coming behind them, signify that we have reached an inflection point in the next frontier in scientific innovation, the effort to turn genes into medicines.

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 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 has already led to licensed therapeutics including Luxturna and Zolgensma. AAV vectors are currently in clinical trials for other rare diseases including Hemophilia A and B, Huntington’s disease, 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; Zynteglo, developed by Bluebird Bio, has been approved for the treatment of beta+ thalassemia, and similar approaches are in development for sickle cell disease and for rare metabolic diseases like cerebral adrenoleukodystrophy.

Besides providing therapeutic options for previously untreatable diseases, gene therapy has the capability to “de-medicalize” conditions that now require frequent medical intervention. In hemophilia or other conditions for which enzyme replacement therapy exists, the possibility of a single vector infusion with a long-lasting therapeutic effect, rather than a treatment that requires ongoing weekly or twice weekly intravenous infusions, represents a remarkably different level of effort and medical sophistication on the part of the patient and the family, and eliminates the need for disciplined adherence to a complex medical regimen.

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 scientifically rigorous and data-driven 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 the Phase 1/2 study is now being evaluated in a Phase 3 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.