- Juno Therapeutics is making strides with its second-generation CAR-T therapy JCAR017, unveiling updated early data Monday that looks competitive in aggressive non-Hodgkin lymphoma (NHL).
- Juno is only three months removed from scrapping its once-lead candidate JCAR015, which was shut down after five patients died from cerebral edema last year. The tragedy set back Juno’s progress in CAR-T development and competitors Novartis and Kite Pharma have since leapt ahead to regulatory submissions with their respective candidates.
- Results from the TRANSCEND study showed JCAR017 led to a three-month overall response rate of 51% across dose levels in 41 patients, sixteen of whom experienced a complete response. Notably for Juno, 60% of patients in the full dataset did not experience any cytokine release syndrome (CRS) or neurotoxicity, two key safety concerns with CAR-T treatment.
While Novartis and Kite will likely be first to market with an approved CAR-T, Juno hopes improvements in the design of JCAR017 will both avoid the safety issues it saw with JCAR015 and lead to better efficacy.
"We continue to look at all sorts of opportunities to improve efficacy, to improve safety," said Juno CEO Hans Bishop in an interview. "I think the data we have just posted on JCAR017 in NHL, I think underscores its potential to be best in class and if that plays out then clearly not coming to market first is not going to be an issue for us."
In addition to reporting results from the full dataset, Juno also cut the data to show results from a core group of patients with diffuse large B-cell lymphoma (DLBCL) that represent the targeted population for a planned pivotal study set to begin later this year.
In that core group, the three-month overall response rate in 32 patients was 66%, with complete responses in 50%. (The full data set included patients with poorer performance and different subtypes of NHL such as mantle cell lymphoma.)
Those rates in the DLBCL core group look better than what has been reported from Kite’s axi-cel CAR-T therapy in DLBCL, although cross-trial comparisons should be treated warily. A readout of three-month data on axi-cel from September showed a 39% overall response and 33% complete response rates. Kite’s data held up over six-months, however, and included more patients.
Given Juno’s backstory with JCAR015, safety results will be closely watched.
In the core group, one patient developed severe CRS and 18% experienced severe neurotoxicity. One patient died, however, from diffuse alveolar damage, which was judged related to the chemo preconditioning regime combined with JCAR017.
Results from the broader data showed a 2% rate of severe CRS and 16% rate of severe neurotoxicity.
Durability of response is a key question for CAR-T, with response rates typically dropping from the best observed response over time. Showing durable responses at six months as well as at the three-month mark will likely be key for regulatory review by the Food and Drug Administration.
Juno’s optimistic here, though.
"I think there is a good reason to believe that the three-month readout is going to be generally predictive of the six-month readout," Bishop said. "We reported today that nine out of 10` patients that were in response at three months are still in response at six."
Jefferies biotech analyst Biren Amin didn’t view Juno’s data as significantly differentiated from the responses seen with Kite’s axi-cel, also known as KTE-C19.
“We think the three-[month] [complete response] rates are in line with KTE-C19 while the safety profile appears slightly better, however it may be more a function of patient baseline characteristics vs. attributes of JCAR17,” Jefferies analyst Biren Amin wrote in a June 5 note.
Shares in Juno fell by more than 10% in Monday trading, perhaps due to continued progress announced by Kite at ASCO.