- Juno Therapeutics is scrapping its lead candidate and plans to redirect focus to a pre-clinical drug similar to another cancer immunotherapy in the company's pipeline. putting it well behind competitors.
- The pivot away from JCAR015 is significant, although not entirely unexpected. Industry followers' optimism in the treatment aimed at relapsed or refractory B-Cell acute lymphoblastic leukemia (ALL) began waning in late November, when Juno halted the Phase 2 ROCKET trial after two patients died from drug-related symptoms.
- "Our investigation into the root causes of the unexpected toxicity seen in the ROCKET trial is close to complete, and although we're confident there are protocol modifications and process improvements that could improve the benefit to risk ratio of JCAR015, we’ve concluded the right strategy for the company and for patients is to discontinue the program and move forward with a defined cell product candidate in this disease setting," Juno CEO Hans Bishop said in a March 1 earnings call.
JCAR015's safety concerns stalled Juno at a time when rivals Kite Pharma and Novartis were sprinting toward filing their own CAR-T drugs for approval. With both companies expecting to submit Biologics License Applications to the Food and Drug Administration early this year, Juno made a point that it wasn't out of the race.
The Seattle-based biotech said its new therapy for ALL will hit the clinic in 2018. The candidate will employ the same defined cell technology — which allows manufacturers to modify phenotype, metabolism and ratio of different types of T-cells in a given treatment — used in its two other drugs, JCAR014 and JCAR017.
The justification there is that JCAR017 touts strong efficacy and fewer safety concerns. The drug wowed at the 2016 American Society of Hematology conference, with data showing overall and complete response rates of 80% and 60%, respectively, in patients with relapsed or refractory B-cell Non-Hodgkin Lymphoma and no instances of severe cytokine release syndrome (CRS), which can lead to death. Juno plans to file JCAR017 for approval sometime next year.
Conversely, 23% of patients receiving JCAR015 demonstrated severe CRS, according to data presented at the American Society of Clinical Oncology in 2015.
"Importantly, these data were generated at the first dosing level of a dose-finding part of the trial – a dose that is meaningfully lower than the doses used in trials for other product candidates in the field in non-Hodgkin lymphoma," Juno's Chief Medical Officer Mark Gilbert said of the Phase 1 JCAR017 trial.
Analysis of the ROCKET trial indicated that rapid expansion of CAR-T cells in patients' bodies correlated with greater toxicity. In turn, patients who received intense conditioning chemotherapy or who had healthier T-cells appear to have an increased risk of that rapid expansion, though cell variations spawned by manufacturing and one's own genetic profile also play a role. The defined cell technology used in JCAR017 should help alleviate some of these problems, according to Juno.
"When we look at JCAR017 at these attributes, they are very tightly controlled and that's translated into a clinical profile ... with an encouraging target and efficacy profile," the company said.
Juno plans to release additional data on the ROCKET trial at a later scientific conference.
Despite the company's optimistic tone on Wednesday, shelving a lead candidate is a hard pill for any biotech investor to swallow. Juno stock reflected this, with shares down almost 10% in Thursday morning trading.