Merri C Moken is a Partner at our New York office
Less than two months after approving the first gene therapy for use in the U.S., that of Novartis's Kymriah for treatment of pediatric patients with acute lymphoblastic leukemia (ALL) 1, the FDA has approved a second single-infusion CAR-T cell therapy. Avoiding the fate of many of its highly-anticipated CAR-T cell predecessors, Axi-Cel (trade name, Yescarta) had no false start; instead Kite Pharma and Gilead Sciences were given an earlier-than-anticipated green light by the FDA to cross the finish line and drive their biologic to market. Yescarta is indicated for adults with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including an aggressive form of non-Hodgkin lymphoma referred to as DLBCL, primary mediastinal large B-cell lymphoma and high grade B-cell lymphoma.2
CAR-T cell therapies capitalize on and direct the patient's immune system to combat cancer. Creating these therapies involves genetically modifying (ex-vivo) the chimeric antigen receptors (CAR) on the surface of the patient's own (autologous) T cells, thus driving the T cells' binding of specific antigens on target cancer cells. In the case of Yescarta, the process takes about 16 days from T cell isolation to infusion into the patient.3 This infusion eventually leads to killing of CD19-expressing cells.
Like Kymriah, Yescarta is an anti-CD19 CAR-T cell therapy. CD19 is a glycoprotein that is expressed by most B cell lymphomas, ALLs, and chronic lymphocytic leukemias (CLLs), thus making it an attractive target in CAR-T cell therapy. However, to date, the approved CD19-targeting CAR-T cell therapies have been associated with neurotoxicity and other severe side-effects that require patient monitoring and co-treatment with other drugs.1,4
Given their different indications, the biologics are not competitive with each other, however it is of note that Yescarta will sell for $373,000, as compared to Kymriah at $475,000,5 presumably due to in part to the significantly shorter manufacturing time for the former.6
It is expected that with continued honing and shortening of the manufacturing processes of the CAR-modified T cell infusions, prices will also decrease. Similarly, with the expected identification in patients of predictors of severe side-effects, physicians should better be able to treat patients to control and ameliorate those side effects. Both achievements will likely make CAR T cell therapies more attractive to insurers and for medical reimbursements.
Footnotes
1 Kymriah package insert
2 Yescarta package insert
4 Id.
5 Reimbursement for Kymriah is outcome based.
6 It takes about 22 days to manufacture Kymriah from the patient's blood.
https://www.cancer.gov/news-events/cancer-currents-blog/2017/tisagenlecleucel-fda-childhood-leukemia
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