JCAR015 Receives Breakthrough Designation for ALL

The FDA has granted the chimeric antigen receptor (CAR) T cell therapy JCAR015 a breakthrough therapy designation as a treatment for patients with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL).

The FDA has granted the chimeric antigen receptor (CAR) T cell therapy JCAR015 a breakthrough therapy designation as a treatment for patients with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL). The announcement came from Juno Therapeutics, the company developing the adoptive T cell therapy.

JCAR015 is comprised of autologous T cells expressing the 19-28z CAR specific to the CD19 antigen. In data from a clinical trial that examined the therapy in 16 patients with ALL, the complete response rate was 88%, according to findings presented at the 2014 AACR Annual Meeting. Patients who responded to the therapy became eligible for a potentially curative allogeneic hematopoietic stem cell transplant.

"The FDA's action is important news for patients who may benefit from the accelerated development of JCAR015 and is an important moment for the field of cancer immunotherapy, which has the potential to meet the need for more effective treatments in a range of cancers," Hans Bishop, the CEO of Juno Therapeutics, said in a statement.

In early April 2014, five early-phase clinical trials exploring CAR T-cell therapies manufactured by Juno Therapeutics were suspended temporarily in response to the deaths of 2 patients with adult B-cell acute ALL. However, on April 19 the studies resumed following adjustments to the safety protocols to address the occurrence of severe cytokine release syndrome.

In general, cytokine release syndrome is a common phenomenon observed with T-cell therapies, which is thought to indicate that the treatment is working. The rare side effect is caused following infusion of the therapy into the patient. At this point, the T cells expand and cytokines are released, causing systemic symptoms such as fever, nausea, chills, hypotension, headache and rash, among others.

In a report on the drug at the 2014 AACR Annual Meeting, researchers noted that severe cytokine release syndrome could be detected using a readily available laboratory test that analyzes serum C-reactive protein. Moreover, once detected, cytokine release syndrome could be treated using corticosteroids or interleukin-6 receptor blockade.

Upon addressing early safety concerns, the clinical trial program resumed with several phase I/II studies currently enrolling participants. A study exploring JCAR015 is currently enrolling at the Memorial Sloan Kettering Cancer Center to assess the T cell therapy in patients with B cell ALL (NCT01044069). Additionally, another trial at the same center is assessing JCAR015 in patients with aggressive B cell non-Hodgkin lymphoma (NCT01840566).

Additionally, on November 17, Juno Therapeutics announced that it had filed an initial public offering for its public stock. Shortly following this announcement, the company also announced that the FDA had granted an orphan drug designation to JCAR015 for ALL.