September 8, 2016
By Alex Keown, BioSpace.com Breaking News Staff
SEATTLE – Shares of Juno Therapeutics are climbing sharply this morning after researchers at Fred Hutchinson Cancer Research Center published a study showing Juno’s JCAR014 CAR-T therapy for the treatment of patients with advanced non-Hodgkin lymphoma was highly effective in patients who had undergone a round of chemotherapy, called lymphodepletion.
The study, which was published in “Science Translational Medicine,” indicates that 50 percent of the 18 patients in the study had a complete response to the disease. Such a response rate is sure to be seen as a validation of CAR-T therapy following the questioning of its efficacy after Novartis shut down its Cell & Gene Therapy unit last month. CAR-T cells are made from a patient’s own immune cells that are then genetically engineered to better identify and kill cancer cells.
Only 8 percent of patients who took the JCAR014 without the previous round of chemotherapy only showed such a response, the company said in a statement.
JCAR014 uses a one-to-one ratio of helper (CD4+) and killer (CD8+) CAR T cells, which join forces to kill tumor cells that produce CD19, a molecule found on the surface of many blood cancer cells, including lymphoma and leukemia. Researchers were able to control the mixture of T cells that patients received during the study, which allowed them to see relationships between cell doses and patient outcomes.
“This study shows that at the right dose of CAR T cells and lymphodepletion, we can achieve very good response rates for NHL patients who have no other treatment options,” Cameron Turtle, an immunotherapy researcher and one of the study leaders, said in a statement.
Of the patients who received a combination treatment of JCAR014 and chemotherapy agents, fludarabine and cyclophosphamide (Cy/Flu) the study showed 82 percent saw an overall response rate and 64 percent saw a complete response rate. The sample of patients also saw a low side effect of neurotoxicity, with only 18 percent demonstrating any symptoms.
Juno said the success of JCAR014 are the key to the development of another cancer treatment in its arsenal, JCAR017. The company is developing JCAR017 for the treatment of blood cancers. In a similar manner to JCAR014, JCAR017 uses a one-to-one ratio of helper and killer CAR T cells, and the company believes it has the potential to be a “best-in-class” treatment for non-Hodgkin lymphoma, chronic lymphocytic leukemia, and adult and pediatric acute lymphoblastic leukemia, Juno said in a statement. JCAR017 is currently in a phase I, multi-center study. Mark Gilbert, Juno’s chief medical officer, said the company hopes the insights from the JCAR014 study will continue to guide the company to the development of more effective treatments for blood cancers.
The early success of JCAR014 is certainly welcome news to Juno following three patient deaths during the mid-stage trial of JCARO15, a CAR-T therapy for patients with relapsed or refractory B cell acute lymphoblastic leukemia. The trial was ultimately placed on hold by the U.S. Food and Drug Administration (FDA), but was allowed to resume in July, only days after a class-action lawsuit was filed against Juno that alleges the company violated federal securities law. The trial though had a revised protocol, only allowing the enrollment of patients with cyclophosphamide pre-conditioning only.
