Select Page

     Arguably one of the greatest advances in immuno-oncology to date, CAR-T therapy is promising a bright future in treating cancer patients by harnessing the power of their own immune system. Everyone knows that white blood cells (leukocytes) are the cells of the body’s immune system. You have different types of B-cells and Screen Shot 2017-09-15 at 4.20.39 PMT-cells. This therapy reprograms the killer T-cells, which are usually responsible for destroying pathogens, to attack cancerous cells instead. Through an expensive lab procedure, the T-Cells are extracted from a patient and the gene for a specific receptor called a chimeric antigen receptor (CAR, hence the name CAR-T therapy) is inserted to their genetic code. This receptor allows the T-cells to bind to a certain protein on the patient’s cancer cells. [1]

     Novartis (NYSE: NVS) is the first pharma company to get this treatment to market with their $475,000 USD tisagenlecleucel CAR-T treatment. Naturally, such a price tag will decrease as the treatment becomes wider-spread but the company has still, despite the breakthrough, come under major scrutiny whether such a price tag is appropriate for a life saving treatment. The main argument against the price tag is that it exceeds what some governments have begun to formally value as a QALY (Quality-Adjusted Life Year). This is the price tag set for one year of life wherein a patient has a quality of life that doesn’t hinder their productivity (seems morally wrong to some to literally put a price on ‘life’, but it is important nonetheless in FDA regulation). Although the U.S. has set such a value the U.K. has valued QALY at around $50,000. [2] From the view of Novartis’, now former (https://bloom.bg/2wxDtSA), CEO Joseph Jimenez the price tag could have been much higher, “I think in this instance we priced at a point where we can get a return, although I have to tell you that the cost of goods, the cost of manufacturing these cells and processing is very, very high”. [3] Jimenez has a good point in that the industry must have good ROI if they are to continue developing such treatments at such a rate.

     Other companies are also hopping on the CAR-T bandwagon such as the recent $12 billion dollar acquisition by Gilead Sciences (NASDAQ: GILD) of the CAR-T therapy developer Kite Pharma (NASDAQ: KITE). [4] Japanese drugmaker Takeda Pharmaceuticals has also made a deal with Noile-Immune for “exclusive options to obtain licensing rights for the development and commercialization of Noile-Immune’s pipeline and products resulting from this partnership.”, they too will hope to bring their own registered CAR-T therapy to market. [5] What will be the effect of all these companies taking advantage of this revolutionary therapy? Well, it is in my opinion that we will see a significant price war where large pharma companies will bring down the prices of their respective CAR-T therapies themselves, without FDA intervention. These prices will descend to the point where costs of developing and bringing the drug to market are met yet some profit is also made. With a smaller profit margin these companies will also redouble their marketing efforts to try to grab the market share of patients who can afford the treatment. This may see an increase in pharma marketing expenditure (for more information on marketing in pharma visit: http://pharmamkting.blogspot.fr/).

     As much positive press as the CAR-T therapy has been getting there are still, however, issues with it. Gilead’s acquisition of Kite, for example has been called not a “one and done” proposition but rather a long bumpy road until registered therapeutic applications can be brought to market.[6] Axi-cel, the drug involved in Kite’s therapy, is being criticized as having a high price to produce and a complex manufacturing process.[6] It is also being compared to bone-marrow transplant treatment, in terms of side effects and risk vs. reward of treatment, to determine which is a better solution (this will have ramifications on the whole CAR-T sector). [6] Until Gilead can solve these problems, the drug will most likely have a very high price tag, taking into account Gilead’s track record of ridiculous pricing with drugs, such as Sovaldi and Harvoni. [2]

     Another drawback is the recent patient death in clinical trials for Cellectis’ (NASDAQGM: CLLS) version of the treatment. Cellectis explained that the patient was a “78-year-old male with Screen Shot 2017-09-15 at 4.20.54 PMblastic plasmacytoid dendritic cell neoplasm, a type of lymphoma, [who] died after experiencing cytokine release syndrome (CRS), a common immune system reaction to CAR-T treatments, that worsened and eventually became fatal”. [7] The FDA placed a clinical hold on Cellectis’ phase 1 trials and is working with Cellectis to redesign the trial protocol, in order to mitigate patient risk. [8] This may have a larger sweeping effect on the CAR-T treatment as a whole, even though the adverse effects demonstrated by other companies’ clinical trials were easily manageable. [7][8]

 

     Despite some of the negative press, the future of CAR-T is very bright indeed. The Fred Hutchinson Cancer Research Center recently developed a procedure that should help to streamline the cell therapy. [9] The procedure involves nanoparticles which target certain cells, such as the T-cells, and deposit proteins which temporarily edit the genes of the cells, inducing therapeutic effects. [9] Such procedures promise to maximise the potential of CAR-T and to, maybe one day, bring it to the masses.

     All in all, the discovery and bringing to market of CAR-T therapy should be heralded as a large leap forward in the immuno-oncology arena and it holds a lot of promise for future research and development.

_______________________________________________________________________________________________________________

Bibliography

[1] “CAR T Cells: Engineering Immune Cells to Treat Cancer.” National Cancer Institute, NIH, Aug. 2017, www.cancer.gov/about-cancer/treatment/research/car-t-cells. Accessed 10 Sept. 2017.

[2] LaMattina, John. “What Can A Company Justifiably Charge For A Cancer Cure?” Forbes, 29 Aug. 2017, www.forbes.com. Accessed 10 Sept. 2017.

[3] Herper, Matthew. “Novartis CEO’s Dilemma: Is $475,000 Too Much For A Leukemia Breakthrough? Or Is It Not Enough?” Forbes, Forbes Magazine, 30 Aug. 2017, www.forbes.com/sites/matthewherper/2017/08/30/novartis-ceos-dilemma-is-475000-too-much-for-a-leukemia-breakthrough-or-is-it-not-enough/#4b36a4f8556e. Accessed 10 Sept. 2017.

[4] Fidler, Ben. “Gilead Makes Long-Awaited Splash With $12B Bet on Kite, Cell Therapy.” Exome, 28 Aug. 2017, www.xconomy.com. Accessed 10 Sept. 2017.

[5] Taylor, Phil. “Takeda joins CAR-T chasing pack with Noile-Immune alliance.” FierceBiotech, 5 Sept. 2017, www.fiercebiotech.com/biotech/takeda-joins-car-t-chasing-pack-noile-immune-alliance. Accessed 10 Sept. 2017.

[6] Lash, Alex. “To Be More Than Quick Splash, Gilead’s CAR-T Purchase Faces Hurdles.” Exome, 28 Aug. 2017, www.xconomy.com. Accessed 10 Sept. 2017.

[7] Fidler, Ben. “Patient Death Triggers FDA Hold For Cellectis’s “Off the Shelf” CAR-T.” Exome, 5 Sept. 2017, www.xconomy.com. Accessed 10 Sept. 2017.

[8] Taylor, Nick P. “FDA hits Cellectis’ off-the-Shelf CAR-T program with clinical hold after first patient treated in phase 1 trial dies.” FierceBiotech, 5 Sept. 2017, www.fiercebiotech.com. Accessed 10 Sept. 2017.
[9] Weintraub, Arlene. “‘Hit-And-Run’ gene therapy nanoparticles could enhance CAR-T treatments.” FierceBiotech, 30 Aug. 2017, www.fiercebiotech.com. Accessed 10 Sept. 2017.