Despite looking to have taken a big step back from cell therapy work this year, Novartis hopes to be first to market a new CAR-T med as it plans to file early next year with the FDA, but rival Kite Pharma is hot on its heels as it starts a rolling submission with the regulator.
Both companies released fresh data over the weekend at ASH, with Kite saying its med KTE-C19 saw 82% of later stage acute lymphoblastic leukemia (ALL) patients (9 out of 11 patients) hit either a complete remission, or complete remission with incomplete or partial hematological recovery, in a top-line look from its phase 1 ZUMA-3 and ZUMA-4 trials.
Unlike in the Juno trial, Kite said it saw no instances of cerebral edema, but safety remains an issue as one patient in ZUMA-3 died from KTE-C19-related cytokine release syndrome (CRS), while another, from the ZUMA-4 test, died from a disseminated fungal infection, although the biotech said this was “unrelated to KTE-C19.”
CRS is a known complication of this new type of therapy, something that happens in some patients when the engineered cells become activated in their body.
Given its data, the company has slapped a new ingredient name on its FDA “breakthrough” med, known henceforth as axicabtagene ciloleucel, and has also kick-started a rolling submission with the FDA for a BLA of its med as a treatment for patients with relapsed/refractory aggressive B-cell non-Hodgkin lymphoma who are ineligible for autologous stem cell transplant.
The biotech said it expects to complete its BLA submission “by the end of the first quarter of 2017.”
Novartis too came out with new data from its phase 2, and also saw 82% (41 out of 50 patients) achieve complete remission or complete remission with incomplete blood count recovery at three months after an infusion of its med CTL019 infusion in young relapsed/refractory patients with B-cell ALL.
“For all patients with complete remission, no minimal residual disease was detected,” the Swiss Big Pharma said, adding that the estimated relapse-free rate among responders was 60% half a year after infusion.
It said this “sets the stage” for a date between CTL019 and the FDA in “early 2017” for pediatric and young adult patients with r/r B-cell ALL, as it goes head-to-head with Kite. Novartis also plans to file with the EMA a little later in 2017 and already has an FDA-like speedy review tag.
In safety terms, nearly half (48%) of patients in its Eliana test were hit with the more serious grade 3 or 4 CRS, although there were no deaths due to CRS.
It did however see 15% of patients experience grade 3 neurological and psychiatric events, including encephalopathy and delirium, but stressed that no grade 4 events were seen.
Back in August, Novartis confirmed reports that it was planning to cut its internal unit dedicated to cell and gene therapy, redeploying most of those 400 employees with around 120 to be cut, as it looked as if the company were slowly exiting the field as it looked to focus more on I/O combos.
It still however appears to have an appetite for CAR-T research and could still be the first to market this new class of cancer med. This was also good news for British biotech Oxford BioMedica, which produces the lentiviral vector expressing CTL019 and has a CAR-T partnership with Novartis, and said it was "pleased" with the "exciting progress" its partner was making.
Juno now seems to be out of the running after a string of deaths from several studies this year severely hampered its prospects of getting a new CAR-T to market any time soon, with big questions over the very future of the biotech itself.
Bluebird bio is a little further behind in regulatory terms than Novartis and Kite, posting some early but impressive data last week from a phase 1 trial showing its anti-BCMA CAR-T cell product candidate, which was given to patients with relapsed and/or refractory multiple myeloma and were heavily pretreated, had an ORR rate of 78%, and with no dose-limiting toxicities and no grade 3 or higher neurotoxicities or CRS coming out of its test.