Expert insight

Cell and Gene Therapies – The Next Transformative Pillar of Medicine

2 October 2015
  • Usman Azam

Genes. Chromosomes. Mutations. Today, these terms are as likely to be overheard in a casual dinner conversation as they are in scientific symposia and medical congresses. While the discovery of DNA dates back to 1869 when Swiss biochemist Johann Friedrich Miescher discovered nucleic acid, it was not until James Watson and Francis Crick published in 1953 their seminal paper in Nature that the science of genetics became commonplace and our vernacular was forever changed. Their finding that DNA replicates by separating into individual strands, each of which becomes the template for a new double helix, was heralded by some to be “the secret of life.” Similar exuberance followed the mapping of human genome in 2003 with the hope that we could now identify all of the “bad actors” in our DNA and find “simple” methods to fix them. However, as history teaches us, early science is almost always confounded by frustration, controversy and yes, failure. This has certainly been true for the field of cell and gene therapies.

The early days of gene therapy were befitting a Greek tragedy. Just as the promise of this new approach was gaining acceptance in the late 80s and early 90s, hopes and confidence were dashed in the wake of some devastating clinical setbacks. It seemed that this nascent field of science was on the verge of being extinguished. However, thanks to the unwavering dedication of undaunted researchers and the remarkable bravery of clinical trial participants, the field of gene therapy not only survived, but it has experienced a remarkable resurgence – due in large part to new methods of transduction which have led to better and safer ways to modify genes.

One of those intrepid pioneers, Dr. Carl June from the Perlman School of Medicine at the University of Pennsylvania, developed an approach which utilizes a disabled lentiviral vector to insert a new gene into a patient’s T cells, producing chimeric antigen receptors (CAR) T cells. These reprogramed T cells aim to hunt, bind to and eliminate cancer cells that have a specific antigen on their surface – such as CD19.

The results from Dr. June’s early trials in blood cancer were impressive. They have garnered headlines in some of the world’s foremost peer reviewed journals. They also led to Novartis’ interest in forming an innovative collaboration with University of Pennsylvania to develop and commercialize CART19 (now called CTL019) and conduct joint research on new CAR T cell therapies. In 2014, Novartis established a dedicated Cell & Gene Therapies Unit to streamline this complex process by combining and leveraging our deep capabilities in Clinical Development, Technical Operations, environment to our own broad scale manufacturing facility in Morris Plains, N.J. The cell reprograming center is the first US Food and Drug Administration (FDA) approved Good Manufacturing Practices quality site for a cell therapy. The facility is currently supporting our Phase II multi-center global study at clinical trial sites in the US, and we expect to expand those trials to the EU by the end of the year.

Novartis is leading the vanguard of investment in cell and gene therapies, and since we announced our commitment to this emerging new field, interest has spread like wildfire across the entire industry, energizing others to join the effort and build a new ecosystem. Additional players and different approaches will only lead to more and better therapies, and I am confident that our collective efforts will have a lasting impact on the lives of many who today have limited, if any, treatment options.

Clearly, many challenges still need to be overcome. Cell and gene therapies are not without side-effects or risks, and defined regulatory frameworks are needed to ensure the safety and efficacy of new products and provide sponsors with a clear path to making new therapies available to patients.

So what will the future hold for cell and gene therapies? Could Miescher have imagined where we would be today? We are tantalizingly close to treating hematologic malignancies with a brand new cell and gene-based therapeutic approach, and learning every day how to harness this potential and apply it to solid tumors, organ transplant and genetic disorders, to name a few. Whatever its shape or form, the recent renaissance in this field strengthens my belief that cell and gene therapies will be the next transformative pillar of medicine – becoming as impactful and disruptive as small molecules and biologics once were.


  • Usman Azam