In August 2017 the Food and Drug Administration (FDA) approved the first gene therapy in the United States, KymriahTM (tisagenlecleucel), manufactured by Novartis, for the treatment of patients up to 25 years of age with refractory B-cell precursor acute lymphoblastic leukemia. This approval was the culmination of 150 years of dogged determination by scientists.
DNA was first identified in the late 1860s by Friedrich Miescher, a Swiss chemist. However, the chemical structure of DNA—the double helix—eluded scientists for almost another 100 years. That scientific mystery was finally solved in 1953 by James Watson and Francis Crick at Cambridge in the United Kingdom.
DNA, the molecule that contains the basic units of heredity―genes—holds the genetic blueprint for the development, growth, function, and reproduction of organisms. Understanding the DNA structure was the initial step in the ability to unravel genetic diseases. Knowledge of the double helix offered the tremendous possibility of manipulating genes to treat and prevent diseases.
About 25 years later, Martin Cline and colleagues at the University of California at Los Angeles (UCLA) attempted the world’s first gene therapy experiments on patients with thalassemia, a potentially life-threatening blood disorder. Because these experiments were not approved by the UCLA Institutional Review Board or the National Institutes of Health (NIH), Cline’s work was severely criticized and he lost his position at UCLA and much of his NIH funding. However, his experiments illuminated issues and initiated debates regarding the scientific validity, ethics, and public health implications of human gene therapy.
For the next 10 years, scientists pursued new avenues of research and guidelines for the testing of gene therapy in patients, emphasizing safe, ethical practices. In September 1990 at the NIH Clinical Center in Bethesda, Maryland, a 4-year-old girl was administered gene therapy as part of a clinical trial to treat an extremely rare immunodeficiency disorder, adenosine deaminase deficiency, which leaves patients defenseless against infections. This study and subsequent experiments forwarded the field of gene therapy but also emphasized the fact that numerous technical hurdles still existed to developing viable gene therapies. Unfortunately, a setback occurred in 1999, when a patient died as the result of a severe immune reaction after the administration of gene therapy to treat his rare metabolic disorder. His death, the first directly related to gene therapy, served to intensify both the ethical debate about and research into improving the safety of gene therapy.
In 2012 the diligence of scientists and clinicians seemed to pay off with the approval of Glybera® (alipogene tiparvovec) by the European Medicines Agency for the treatment of a rare lipid metabolic disorder, lipoprotein lipase deficiency. However, in 2017 Glybera was withdrawn from the European market due to a lack of patients, the cost of the drug, and questions about its efficacy. Today, gene therapy faces new challenges in terms of economic considerations and healthcare policies driven by a “return on investment” mindset.
In July 2017 the US FDA accepted a biologics license application from Spark Therapeutics and granted priority review for its gene therapy drug voretigene neparovec for use in the treatment of a rare, vision-impairing retinal disorder. A decision by the FDA is expected within 6 months. This recent news, along with the approval of the first gene therapy in the United States, Kymriah, is ushering in a new era of medical innovation, in which reprogramming or replacement of faulty genes may offer a novel approach to the treatment of rare inherited disorders.
About Connexion Healthcare
Connexion Healthcare is a full-service global provider of strategic medical and scientific communications with decades of experience providing exceptional service to the pharmaceutical industry. We provide services through 2 Centers of Excellence—Oncology and Rare Disease—and possess core expertise in these therapeutic areas and their marketplaces.
The Connexion Healthcare Rare Disease Center of Excellence specializes in communicating the science behind rare diseases and orphan drugs. We strategically partner with industry leaders in the rare disease community to proactively connect all stakeholders in launching products to underserved patient populations. Our team comprises skilled communications experts who plan, develop, and disseminate scientific communications based on their advanced knowledge of the science, the patient journey, healthcare providers, and the orphan drug approval process.
At Connexion Healthcare, our cross-functional teams navigate complicated treatment and market landscapes by elucidating the appropriate pathways to brand success. We understand how brand strategy drives market share. Since launching its dedicated Rare Disease Center of Excellence, Connexion Healthcare has developed prelaunch, launch, and postlaunch communications in numerous rare diseases and disorders: congenital and genetic, movement, metabolic, and lysosomal storage disorders; lung, blood, skin, and endocrine diseases; and rare cancers.
For further information regarding the Rare Disease Center of Excellence at Connexion Healthcare and how we can develop rare disease communications to differentiate therapies by their unique attributes, contact:
Susan Stein, MPH
SVP, Strategic Services and Business Development