Rewrite the textbooks: treating disease has been turned inside out

KymriahTM launches great expectations

November 2, 2017
In the broad sense, gene therapy harnesses the body’s own innate capacity to heal itself.

Kymriah™ was first in September 2017. Yescarta™ followed in October. We expect to see Luxturna™ approved in January 2018 or earlier. Decades of research by hundreds of scientists contributed to the development of these drugs. This article will take a closer look at the development process – the long pipeline – from which these drugs emerged.

Earlier important breakthroughs in gene therapy

The first gene therapy trial was done at the National Institutes of Health (NIH) Clinical Center in 1990.1 White blood cells were removed from a young girl with adenosine deaminase (ADA) deficiency, a genetic disease which left her defenseless against infections. Healthy genes for making ADA were added to the white blood cells in the lab. The corrected white blood cells were reinfused. She received repeated treatments over two years and fully recovered. Today, she is a thriving millennial.

It’s been a bumpy ride 

The clinical trials for these gene therapy drugs have been tough. There is still a lot to learn.

In 2000, just 10 years after the first success at the NIH – several patient deaths in gene therapy trials attracted media attention. Nearly 700 reports of serious adverse events (serious deteriorations or deaths) were submitted to the FDA and the NIH. But those reports were submitted late. The delay indicated that some researchers may not have been following guidelines.

Gene therapy is normally carried out on terminally ill patients. Those deaths may have been caused by the treatment technique, by the original condition, by treatment side effects or something else entirely. The purpose of the NIH reporting was to share data with other scientists conducting similar research to move the technology forward. “It is important to make these reports promptly so that appropriate measures can be taken by other researchers to safeguard the health of their patients,” said an NIH official.2

Another dozen years later, in 2012, seven-year-old Emily Whitehead of Philipsburg, PA, was the first person to try what is now called Kymriah. Her leukemia went into complete remission within three weeks of treatment.3 Clinical trials continued, and the FDA approved Kymriah in September of 2017.

Doctors see new hope

Doctors aren’t known for effusive language, but their comments around the launch of Kymriah provide a hint of the potential they see in gene therapy.

Gene therapy quotes

“Certainly for blood cancers, this is a game changer,” said Stephan A. Grupp, director of the cancer immunotherapy program at Childrens’ Hospital of Philadelphia.3

Kymriah is “… a transformative therapy … it represents an entirely new class of cancer therapies that holds promise for all cancer patients.” said Dr. Crystal L. Mackall, associate director of Stanford’s Cancer Institute.3

“This approval will open the floodgates for these kinds of therapy to be used in many different leukemias, lymphomas, solid tumors, myelomas,” said Dr. Prakash Satwani, a pediatric hematologist-oncologist at Columbia University Medical Center. “I think this is just the beginning of a new era of gene therapy.”4

FDA Commissioner Scott Gottlieb, predicted that this new approach to cancer treatment will “change the face of modern medicine.” Gottlieb himself is a survivor of blood cancer.3

One member of the FDA advisory committee called it “the most exciting thing I’ve seen in my lifetime” for childhood leukemia.”4

Trials continued and the field developed

Certainly, optimism around CAR-T therapy has increased, but it’s still a slow process with setbacks. In 2016, the FDA stopped clinical trials of another CAR-T therapy, from Juno Therapeutics. Designed to treat ALL, JCAR015 caused fatal cerebral edemas in three patients.5

Then in September 2017, the French biopharmaceutical company Cellectis had two phase 1 trials of CAR-T drugs stopped, following the death of one patient. Cellectis is working with the FDA to redesign the study. Cellectis drugs are “off-the-shelf” CAR-T drugs. This means that they don’t use a patient’s own T-cells, but instead collect T-cells from donors.5 The Cellectis offerings may continue testing at another point.

“These are very potent drugs, good and bad,” said Sandip Patel, medical oncologist and assistant professor of medicine at the U.C. San Diego Moores Cancer Center, in a phone interview. “…people can die from the side effects.”6

People dying to try anything

Research shows that 61 percent of American adults look online for health information.7 Websites for cancers and conditions provide consumers with a range of information. The websites cover causes, symptoms, treatments and support groups. And they display information on how to find out about clinical trials for treatments in development. Often they include information on complementary and alternative medicines.

What’s ahead?

Around the world, nearly 900 gene and cellular therapy clinical trials are underway in 2017, according to the Alliance for Regenerative Medicine (ARM). More than 70 of these trials are in phase III (the phase just prior to FDA final review).8 Half of the clinical trials are in oncology.

This is the future

With science advancing at such a rapid rate, how will plan sponsors ensure these treatments are used in the most cost-effective manor? How will they track and manage the expenses of these costly new treatments? With many potentially curative treatments approved with just a few months of follow-up, how will life-time effectiveness be assessed? What if the treatment that is supposed to last a lifetime only lasts a few years?

These drugs raise important questions. Prime’s integrated model can give plan sponsors a clear view of total costs. And our leadership in integrated care is the first step in managing through these exciting changes.


  1. “ADA The First Gene Therapy Trial.” Office of NIH History. National Institutes of Health. © 2017 National Institutes of Health. Accessed at:
  2. “Earlier Gene Test Deaths Not Reported,” By Deborah Nelson and Rick Weiss Jan, 31, 2000. The Washington Post. © 1996-2017 The Washington Post. Accessed at:
  3. “Hailing a breakthrough in fighting cancer, FDA approves gene therapy that functions as a ‘living drug,’” by Melissa Healy. Los Angeles Times. August 30, 2017. Copyright © 2017, Los Angeles Times. Accessed at:
  4. “A medical breakthrough that hacks genes to fight cancer just got approved, and it’s the beginning of ‘a big new field of medicine,” by Lydia Ramsey. Business Insider, Aug. 31, 2017. © 2017 Business Insider. Accessed at:
  5. “FDA hits Cellectis’ off-the-shelf CAR-T program with clinical hold after first patient treated in phase 1 trial dies,” by Rick Paul Taylor, Sept 5, 2017. FierceBiotech. © 2017 Questex LLC. Accessed at:
  6. ”Kymriah and the CAR-T roller coaster,” by Josh Baxt, Sept 6, 2017. © 2017 Breaking Media, Inc. Accessed at:
  7. 61% of American Adults look online for health information,” Washington, DC, June 11, 2009. Numbers, Facts and Trends Shaping your World. Pew Research Center Internet and Technology. Copyright 2017 Pew Research Center. Accessed at:
  8. Q2 2017 Alliance for Regenerative Medicine Quarterly Data Report. Published by the Alliance for Regenerative Medicine. Accessed at:

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