For those interested in staying up to date with the latest developments in biotechnology it is impossible to overlook the developments of chimeric antigen receptor therapy (CAR-T) and the potential it holds for treating cancer. The most pivotal moment came on Aug. 30 when Novartis (NVS) announced approval for Kymriah™ (tisagenlecleucel) for treating children and young adults with B-cell acute lymphoblastic leukemia (ALL) that is refractory or has relapsed at least twice.
On the surface, it is easy to overlook the importance of this approval due to the small population size Kymriah™ treats. This type of treatment is a transformative moment in the pharmaceutical industry and holds great potential for patients and investors.
But first what exactly is CAR-T? Pharmaceuticals can be broadly broken down into three groups. The first group is small chemical molecules and includes blockbusters such as Lipitor™ and Prozac™. The second bucket is biologics, which are more complex and require the use of bioreactors and engineered cell lines to manufacture. Biologics encompass proteins such as antibodies and traps and include other blockbusters such as Humira™ and Eylea™. Last are therapies such as CAR-T which are developed by taking a patient’s blood, isolating T-cells and engineering them to attack and kill cancer cells.
What should be kept in mind is that while this treatment is new, the reported results are often nothing short of spectacular. Novartis was sure to point this out in its press release stating “First-in-class therapy showed an 83% (52/63) overall remission rate in this patient population with limited treatment options and historically poor outcomes.”
Despite these impressive results there are concerns the future holds. First is the enormous complexity associated with developing CAR-T therapies and large-scale production. Every patient is different and therefore every patient’s T-cells need to be treated individually. There are physiological concerns as well following administration such as cytokine release syndrome which has resulted in patient death. Last are logistics due to the fact that the number of patients seeking treatment will grow and so will the needed facilities and manpower. This complicated process should also shine some light on the current price of Kymriah™, which has reported to be $475,000. Readers should also know that because Novartis is pursuing an outcome-based approach with Kymriah™, the $475,000 is only paid if the patient responds in the first month of treatment.
It is also worth noting that to put the $475,000 price tag in perspective, treating a patient with leukemia under the age of 65 is already very costly and consists of about $197,000 for end-of-life treatment, initial costs of $41,400 and continuing treatment costs of $9,000 per year yielding a five-year survival rate for all of 67%.
Due to the above challenges of manufacturing and risks associated with R&D for CAR-T, transitioning from a purely academic initiative to a commercial initiative could arguably not have been done without the help of the National Institutes of Health (NIH) which continues to fund CAR-T research with greater funds year after year.
This investment in research has paid off with not just Novartis clinching the first FDA approval, but several other notable companies with CAR-T therapies on the path to approval. Such companies include Kite Pharma (KITE), recently acquired by Gilead (GILD), bluebird bio (BLUE), Cellectis (CLLS) and Juno Therapeutics (JUNO) among others. While none of these companies have approved drugs in the market, they are evaluated in the billions of dollars due to their promising results. A breakdown of these companies and number of their therapies in clinical trials is provided below as well as their historical stock price over three years.
| Company | Phase 1 | Phase 1/2 | Phase 2 | Phase 2/3 | Phase 3 | Market cap (billions) |
| Juno Therapeutics | 9 | 2 |  |  |  | 5.29 |
| Kite Pharma * | 1 | 4 | 3 | 1 | Ă‚ | 11.9 (acquired) |
| bluebird bio | 2 | 1 | Ă‚ | 1 | 1 | 6.0 |
| Cellectis | 2 | Ă‚ | Ă‚ | Ă‚ | Ă‚ | 1.02 |
| *T cell receptor (TCR) therapies not included in above count | ||||||
While the focus of these companies is primarily on treating liquid tumors (such as AML, CML, ALL and CLL-red boxes), the market landscape will begin to change even more drastically if CAR-T becomes effective against solid tumors – specifically, cancers that have very high mortality rates such as pancreatic and lung (green boxes). The below chart indicates the impact CAR-T could have, especially if the success rate of treating solid tumors can match what is reported with Kymriah™.
One last thought that should be kept in mind is when/if there is a turning point in the line of treatments for CAR-T vs. conventional treatment. At the moment, conventional treatments such as invasive surgery, radiation and chemotherapy remain first-line treatments. It is debatable if treatments such as Kymriah™ will remain last-line treatments as manufacturing costs decline, outcomes are tracked and more competition enters the market. CAR-T truly has the potential to change how cancer is treated, and we are witnessing the beginning of what many believe and hope is a new and promising chapter in the field of medicine.
Disclosure: I do not have positions in the stocks mentioned.
Resources
- NIH Research Portfolio Online Reporting Tools (RePORT) - Text Search: "chimeric antigen receptor" (Advanced); Search in: Projects Limit to:Project Abstracts; AdminIC: All; Fiscal Year: 2016; 2015; 2014; 2013; 2012; 2011; 2010; 2009; 2008; 2007; 2006
- Cancer Facts & Figures 2017
- Projections of the Cost of Cancer Care in the United States: 2010–2020
