Kite Pharma was off by 15% in morning trading after it announced the death of a patient in late April of cerebral edema—the very same fatal outcome that beset rival Juno’s Rocket trial, killing five people and its CAR-T program for JCAR015.
The cerebral edema came from a trial of KTE-C19 (axicabtagene ciloleucel), Kite’s cutting-edge CAR-T medication, which is in a tight race with Novartis to gain the first FDA approval for this new class of cancer medicine. Novartis has as yet not seen deaths from this cause in its trials, although further study data from the Big Pharma, namely Juliet is still to be seen.
The trial was in non-Hodgkin’s lymphoma, and the death was generally unexpected—Kite has thus far not shown any deaths from this cause, although it was responsible for five deaths in trials for its rival Juno Therapeutics last year.
For Juno, this appeared to be drug-related, despite initial protestations from the biotech that it came as a result of other preconditioning meds.
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Investors were therefore spooked by Kite's news from its Zuma-1 safety expansion cohort, sending its shares down 15% after the news was revealed. As EvaluatePharma put it: “While patient numbers are far too small to draw firm conclusions, an uncomfortable fact is that KTE-C19 is an extremely similar CAR construct to JCAR015, differing only in the binding region it uses. The precise cause of cerebral edema with CAR-T is not understood, but it had surprised some that none had previously been seen with KTE-C19, given its similarity with JCAR015.”
Kite, however, is looking to ease concerns. The company told FierceBiotech: “This was a singular event and as you know, Grade 5 events are not unexpected in studies involving patients who are suffering from rapidly progressing cancer that is refractory to treatments. The Safety Expansion Cohort was initiated after the close of the registrational trial.
“We have completed the U.S. portion of the Safety Expansion cohort, having enrolled and treated the planned 30 patients. The key measures studied in this cohort is the use of an anticonvulsant, and early use of tocilizumab to minimize the risks of severe CRS or Neurologic Events associated with anti-CD19 CART therapy.
“An early analysis of the adverse event profile suggests that this approach may indeed reduce the risk of severe CRS. In the 30 patients treated to date, we have only two reports of Grade 3 CRS (which includes this patient).”
Kite explained that the man who died “was a very sick patient with explosive disease, meaning a rapidly progressive and symptomatic disease (including tumor, fever, pain, worsening liver function, and a new onset accumulation of fluid in the lung).”
It added that the patient had shown inadequate responses to both first- and second-line therapies, and that “those involved in the care felt that CAR-T therapy was the only remaining option.”
David Chang, Kite’s CMO and EVP of research and development, said on the call announcing the death that the biotech: “Will be amending the patient consent form to inform the current and future study participants of the potential risk of fatal cerebral edema.”
He added that: “In this particular case, the explosive nature of the patient's lymphoma immediately prior to and up to the day of Axi-Cel therapy is a consideration and is being further investigated.”
All development studies of the drug are continuing as planned. “The FDA looks at the totality of data and it is important to note that the overall incidence of KTE-C19 related grade 5 events remains at 2% in approximate 200 patients treated in our study supports the benefit of axi-cel and KTE-C19. If patients treated in the NCI studies are included, over 300 patients have been treated with KTE-C19.”
The spokeswoman added: “We remain confident in the KTE-C19 development program and look forward to review by the FDA and potential approval by the end of 2017.”
Analysts at Jefferies also saw no reason to panic. In a note to clients, it said: “We see minimal read-through from the cerebral edema death to axi-cel approval. In the 30 pts KITE treated in the Zuma-1 expansion study, two pts experienced Grd 3 CRS and one pt died of cerebral edema in late April.
“Mgmt commented that the patient that died had very aggressive disease and was in poor health prior to infusion of Axi-cel. Specifically, he had a high fever (indicating an active immune system), worsening liver function and showed cytokines in the CSF. We spoke to mgmt about the death and they indicated that nothing was different about the mfr'ing process or cell product characteristics.
“However, KITE provided all details to FDA regarding this patient. Because this was observed in 1 pt that was in poor health, we do not believe this significantly affects the chance of approval for Axi-cel in aggressive NHL and do not expect a clinical hold to be issued in any ongoing trials. Rather, based on mgmt's comments we think the 30 pt safety data may support the tolerability profile of Axi-cel and earlier use of treatments to mitigate CRS and we look to the presentation of the full results for more info,” the analyst firm concluded.