A Disruptive Innovation to Fight and Cure Intractable Diseases

Several important facets of health care often arrest general attention. These are also widely discussed, analyzed and argued vehemently – with each person or group trying to justify one’s own point of view. Among these, following 6 critical areas, broadly dominate the deliberations:

  • Incredible advancement in the medical science driving health care,
  • Infrastructure, facilitators and providers of health care,
  • ‘Wolves of health care in sheep’s clothing’, as described by many
  • Large populations facing inadequate availability and access to health care,
  • The need for Universal Health Care (UHC)
  • Public investments, policies and regulations governing health care.

In this article, I shall focus only on the first area – incredible recent advancement in the medical science driving health care, especially the very recent developments on a disruptive innovation called ‘Gene Therapy’.

Gene Therapy:

As some would know, one of the latest developments in the pharma world, relates to marketing approval in the United States and Europe of ‘Gene Therapy’ – a disruptive innovation in the medical science.

This technique of treatment using genes to manage, cure or prevent many intractable diseases are fast gaining ground globally, including India – at a slower pace, though. As I said, in America, the first gene therapy has already obtained the approval of the US-FDA in August 2017, closely followed by the second in October 2017, with the third waiting in the wings. In the European Union (EU), the first gene therapy was approved in 2012, but faced some commercial issues that I shall discuss later in this article.

During approval of the first gene therapy in the United States (US), the FDA Commissioner Scott Gottlieb reportedly said, this new frontier in medical innovation has the ability to reprogram a patient’s own cells to attack a deadly disease, such as cancer, creating an inflection point to treat, and even cure many intractable illnesses.

According to an October 10, 2017 publication of the U.S. National Library of Medicine, gene therapy may allow doctors to treat a disorder by inserting a gene into a patient’s cells instead of using drugs or surgery. Extensive research is ongoing, adopting several approaches to this treatment, including:

  • Replacing a mutated gene that causes disease with a healthy copy of the gene.
  • Inactivating, or “knocking out,” a mutated gene that is functioning improperly.
  • Introducing a new gene into the body to help fight a disease.

Thus, gene therapy is fast emerging as a promising treatment for a number of life-threatening diseases, including inherited disorders, some types of cancer, and certain tough to treat viral infections. That said, the technique being risky, is still under study to make it safer the patients. Currently, it is being tested only for diseases that have no other cures.

The first approval of gene therapy in the United States:

On August 30, 2017, US-FDA took a historic decision with its approval for the first ever gene therapy in America – meeting an unmet need in its true sense, and thus creating a major milestone in medical science. US-FDA approved this treatment for certain pediatric and young adult patients with a form of Acute Lymphoblastic Leukemia (ALL) – resistant to standard treatment, or which often relapses. The overall remission rate within three months of this treatment was found 83 percent in clinical trials.

This path-breaking therapy (tisagenlecleucel) is named Kymriah, and is made by Novartis. Nevertheless, it is worth noting that the treatment was developed by a group headed by Carl H. June  at the University of Pennsylvania and licensed to Novartis.

A customized treatment:

The US-FDA approval letter to Novartis says, “Kymriah is a genetically modified autologous T-cell immunotherapy. Each dose of Kymriah is a customized treatment created using an individual patient’s own T-cells, a type of white blood cell known as a lymphocyte. The patient’s T-cells are collected and sent to a manufacturing center where they are genetically modified to include a new gene that contains a specific protein (a chimeric antigen receptor or CAR) that directs the T-cells to target and kill leukemia cells that have a specific antigen (CD19) on the surface. Once the cells are modified, they are infused back into the patient to kill the cancer cells.”

Nevertheless, Kymriah can cause life-threatening side effects, such as dangerous drops in blood pressure. This has prompted US-FDA to caution that hospitals and doctors should be specially trained and certified to administer this therapy, and require stocking of drugs to control severe reactions, if and when required.

The price tag is jaw dropping:

As  reported by New York Times (NYT), Kymriah will be given to patients just once and must be made individually for each, costing US$ 475,000. Novartis reportedly has said, if a patient does not respond within the first month after treatment, there will be no charge. The company also said it would provide financial help to families who were uninsured or underinsured. This is indeed a commendable gesture.

The second USFDA approval for gene therapy:

Just about a week ago, on October 18, 2017, US-FDA approved Yescarta (axicabtagene ciloleucel) of Kite Pharma Inc. – a Gilead company. This is gene therapy is to treat adult patients with certain types of large B-cell lymphoma who have not responded to or who have relapsed after at least two other kinds of treatment.

Initially, 54 percent of patients on Yescarta reportedly had complete remissions with their tumors disappearing. Another 28 percent had partial remissions, where tumors shrank or appeared less active on scans. After six months, 80 percent of the 101 were still alive.

Just as Kymriah, Yescarta will also reportedly be introduced gradually, and be available only at centers where doctors and nurses have been trained in using it. This is, again, due to its serious side effects, which include high fevers, crashing blood pressure, lung congestion and neurological problems.

As reported, Kite Pharma hopes that Yescarta will eventually be approved for earlier stages of lymphoma, rather than being limited to patients with advanced disease who have been debilitated by multiple types of chemotherapy that did not work.

Yescarta will cost less than Kymriah at US$ 373,000 per patient. This is a single dose treatment to be infused into a vein, and must be manufactured individually for each patient. About 3,500 people a year only in the United States is estimated to be candidates for this therapy.

Yet another gene therapy is likely to get US-FDA approval soon:

Close on the heels of these two developments, yet another gene therapy is likely to get US-FDA approval in the coming months. On October 12, 2017, Spark Therapeutics – a gene therapy company in the United States, reportedly won unanimous support from a US-FDA advisory panel for its gene therapy – Luxturna (voretigene neparvovec), after the experts concluded that the benefits of this gene therapy outweighed its risks.

Luxturna – a one-shot treatment, has shown to reverse blindness by restoring vision in children with an inherited form of blindness, and shows potential to restore blood-clotting function to hemophiliacs, or even cure rare diseases outright. However, as the analysts estimate, the cost of Luxturna will be hefty, which could even be more than Kymriah of Novartis – at US$ 1 million per patient.

The first gene therapy in Europe was not commercially viable:

As stated above, in 2012, the first gene therapy – Amsterdam-based Uniqure’s Glybera (alipogene tiparvovec), was approved by the European Medicines Agency (EMA) for the EU market. The product was indicated for treatment of rare inherited disorder – lipoprotein lipase deficiency (LPLD).

However, with treatment cost of €1m+ per patient, Glybera was reportedly the most expensive therapy ever approved in Europe. Interestingly, in April 2017, Uniqure decided to terminate post-marketing studies required for prolongation of its existing EU conditional market approval, for its extremely limited usage, making the product commercially non-viable.

These four developments give me a sense of both – the fast pace of progress of gene therapy and also its possible commercial vulnerability, due to astronomically high prices coupled with a limited number of current usages linked to the specific disease types.

Gene therapy research in India:

According to the paper titled, “Gene therapy in India: a focus,” published by the Journal of Biosciences in June 2014 – ‘starting from 1998, the Indian government is playing a leading role in the advancement of gene therapy research in India by providing enormous financial support to scientists and clinicians through its various funding agencies like Department of Biotechnology (DBT), Department of Science and Technology (DST), Indian Council of Medical Research (ICMR), etc.’

India is not far behind other Asian countries in the field of gene therapy. In Asia, China is the leader with 16 research laboratories, followed by Japan (13), India (10), South Korea (4), Israel (3) and Taiwan (3), the paper says.

The laboratories established in India to conduct gene therapy research are: Advanced Centre for Treatment, Research and Education for Cancer, Mumbai (1998), University of Delhi (2002), Saha Institute of Nuclear Physics, Kolkata (2004), Indian Institute of Science, Bengaluru (2005), Actis Biologics Private Limited (2005), Mumbai, Center for Stem Cell Research, Vellore (2010), Vellore Institute of Technology, Vellore (2012), Institute of Life Sciences, Bhubaneswar (2012), Narayana Nethralaya, Bengaluru (2013).


As deliberated above, gene therapy reflects an incredible advancement in the medical science driving health care. This is primarily because, the disruptive innovation is aimed at treating genetic diseases at the molecular level by correcting the defective genes.

The fact, as captured in the worldwide gene therapy data table, that between 1989 and February 2016, over 2,300 gene therapy clinical trials have been conducted – 93 of which being in phase III while 3 in phase IV, further vindicates the rapid pace of evolution of this science.

As stated before, the critical process of this treatment reportedly involves ‘introduction of new genes into cells, to restore or add gene expression, for the purpose of treating disease. Most commonly a mutated gene is replaced with DNA encoding a functional copy. Alternatively, DNA encoding a therapeutic protein drug may be introduced.’ However, the exorbitant current cost of this novel treatment, for various reasons, severely limits its access to a vast majority of the global population, at least for now.

Be that as it may, the disruptive medical innovation culminating into gene therapy of date, is expected to open new vistas of opportunity to fight and cure several life-threatening intractable diseases. This game changing advancement in the medical science, no doubt, would help provide a new lease of life only to some, mostly due to its price barrier. Nevertheless, for many, it does carry a new hope for access to this life changing therapy – probably at some point of time in future. God willing!

By: Tapan J. Ray 

Disclaimer: The views/opinions expressed in this article are entirely my own, written in my individual and personal capacity. I do not represent any other person or organization for this opinion.

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