Juno Therapeutics will resume its Phase II ROCKET clinical trial of its acute lymphoblastic leukemia candidate JCAR015 following the FDA’s lifting of a partial clinical hold imposed last week following the deaths of three patients.
Juno said last night it will continue enrollment by returning to the trial’s original protocol of using cyclophosphamide alone as a preconditioning drug. During the second quarter, Juno changed the protocol to precondition patients by using a combination of cyclophosphamide and fludarabine—a change the company has blamed for the cerebral edema deaths of the three patients, all under age 25.
JCAR015 is a CD19-directed chimeric antigen receptor technology (CAR-T) product candidate that has been under study in ROCKET in adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia.
The clinical hold had been expected to push back Juno’s earlier plans to pursue FDA approval next year for JCAR015. The company has said it will discuss a revised development timeframe for JCAR015 when it holds its quarterly conference call with analysts next month.
News of the trial resumption led to a nearly 25% jump in Juno’s share price, which traded after hours at $34.69 as of 8:04 a.m., up from yesterday’s close of $27.79.
“Many investors expected a more lengthy FDA review process of the JCAR015 trial (and potentially other CAR-T programs) and feared that a higher-degree regulatory scrutiny could increase the development risk of CAR T cell,” Leerink Research said in a note co-authored by analysts Michael Schmidt, Ph.D., Jonathan Chang, Ph.D., and Varun Kumar, Ph.D. “While it may take several weeks to reopen all clinical sites of the ROCKET trial, we believe the trial shouldn't be delayed by more than ~3 months.”
Canaccord healthcare analyst John Newman, Ph.D., wrote in a note to investors that he considered the FDA’s lifting of the Juno clinical hold “encouraging for all CART companies. Importantly, we believe that FDA views each clinical trial and construct differently, but that the agency was able to rapidly gain comfort with Juno's new clinical plan.”
Dr. Newman added that rival CAR T cell therapy developer Kite Pharma was still likelier to generate more revenue than Juno with KTE-C19, which last week completed patient enrollment in the Phase II portion of the ZUMA-1 trial in patients with diffuse large B-cell lymphoma.
“We remind investors that Kite's revenue opportunity in their lead relapsed/refractory DLBCL indication is nearly 4x larger than Juno's lead relapsed/refractory ALL indication, giving a distinct advantage to Kite, in our view,” he wrote.
Juno has also said that the clinical hold on the ROCKET trial would not affect plans for its other CD19-directed CAR T-cell product candidates, including JCAR017, for which the company anticipates a 2018 approval.
[This report has been updated to include comment from Canaccord healthcare analyst John Newman, Ph.D.]