Gene therapy is now, finally, a new weapon in our arsenal against cancer partly thanks to, of all things, the HIV virus. The world’s first chimeric antigen receptor T-cell (CAR-T) treatment was approved by the Food and Drug Administration at the end of last month, a treatment developed by one Dr. Carl June at University of Pennsylvania in partnership with Novatris AG (NVS, Financial).
The drug is called Kymriah; and it could be the most effective, and the most dangerous, leukemia treatment available today. Phase II trials showed an 83% complete remission rate with zero minimum residual disease markers. The five-year survival rate for this type of cancer is less than 10%.
Despite the obvious efficacy though, the long-term risks associated with this method of cancer treatment are not yet fully known. In order to understand why, we need to go into how it works.
In 2011, June was able to attenuate the HIV virus to carry the genetic code for the antigen present on B-cells, the cancerous cells in acute lymphoblastic leukemia. HIV is really efficient at getting inside T-cells, which are the virus’ target cells. Reprogramming HIV to deliver the code for B-cell antigens, rather than the code for producing more HIV viruses, enabled the infected T-cells to recognize B-cells and kill them.
The dangerous part is not actually the HIV, which, once reprogrammed in this way, has zero chance of causing AIDS. The dangerous part is introducing T-cells programmed to kill B-cells into the body. The immediate danger of the treatment is an immune system in complete overdrive. It suddenly has a lot of B-cells to kill and releases cytokines in order to so. If the cytokines are not controlled, they can kill the patient. There are treatments that can mitigate the release and patients are under constant monitoring post-treatment to make sure they can get through it. One of the conditions of Kymriah’s approval is hospitals must have a Roche Holding Ltd. (RHHBY) medication called Actemra available, which is known to block a certain cytokine release.
But there are other questions we will not know the answer to until much later, perhaps years from now. Since the new T-cells target both healthy and cancerous B-cells, what are the long-term effects of an immune system constantly attacking a patient’s own blood? Second, doctors do not know how long these cells last. They are not produced in-house, so there is a danger the cancer may return once they die off.
As scientists look for answers to these questions and Kymriah enters the oncology market, it will be the other CAR-T players who may be affected the most. These include Gilead Sciences (GILD, Financial), which just announced its intentions to acquire CAR-T company Kite Pharma (KITE, Financial), Juno Therapeutics (JUNO, Financial), Bluebird Bio (BLUE, Financial) and a smattering of others.
Novartis may be the first to market, giving it an advantage over its competitors, but the others have an important advantage in being slightly behind. They will be able to adjust if problems surface on the long end of the Kymriah treatment.
Disclosure: No positions.
