Juno Therapeutics $JUNO may be playing catchup in CAR-T. But if the latest cut of its 3-month DLBCL data at the top dose holds up, the biotech won’t be playing for second — or third — place.
In their abstract out for ASH this morning, Juno execs spelled out a key piece of data for the high dose arm of the early study on JCAR017. Zeroing in on that one snapshot, researchers say they tracked an 80% overall response rate and a 73% complete response rate at 3 months for the high dose among a “pivotal core” group of 15 patients.
Gilead’s Kite and Novartis saw a slight decline in the CR rates to the low 30s going from 3 to 6 months, leaving Juno a window for considerable improvement.
To be sure, Juno still has a long way to go after its lead JCAR015 proved to be a lethal, toxic disaster in what was intended to be a pivotal study. But the biotech isn’t at all content to be remaindered to the section of the industry that counts the number of patients killed in a failed study. Instead, Juno believes that its follow-up program will prove that the big sums gambled on its technology will show that they came up with a better CAR-T, with a more effective manufacturing process and a safer profile that will ultimately carve out a big place for itself in the market.
Investors liked what they were seeing, driving up Juno’s shares by 10% this morning.
Everything is riding on this one. There won’t be much chance for a third shot at success.
What’s different this time?
“The analogy I’ll give you,” says R&D chief Sunil Agarwal: “Small changes in the antibody world can make big differences; all CARs are not the same.”
There’s more to come at ASH, he adds, where they can review the response for a bigger group of patients. But the essential efficacy and safety profile on display today, he adds, isn’t going to change.
Says Agarwal: “I think these data continue to support a best-in-class profile.”
For one, there’s the switch to the 4-1BB costimulatory domain, which allows for a slow and steady activation that sets the foundation for a more durable response.
But that’s a feature that Novartis’ CAR-T shares as well. Juno CEO Hans Bishop tells me the “precise production” values used now in making the therapy from cells extracted from patients is just far more precise.
“We know CD4 and CD8 cells act different, CD8 cells are more potent,” says Bishop. Getting the right mix with a measured expansion of cells now is part of a precisely arranged production recipe that distinguishes JCAR017 from the rest, he asserts.
Bishop isn’t talking exact pricing yet, and won’t until much later in the game. But he does want people to understand that to be competitive here involves beating out some steep existing costs in treating DLBCL or ALL. Safety, he says, will play a big role in that.
The latest update on the data remains with 1 patient suffering from cytokine release syndrome, and 14% with neurotoxicity running from Grade 1 to Grade 4. That’s not a perfect score, by any means, but in this world Bishop feels the numbers give Juno an advantage over worse issues with the market leaders.
Close to two thirds of the patients in their study never exhibited any signs of toxicity, either cytokine release syndrome or neurotoxicity, which ultimately destroyed Juno’s lead therapy, JCAR015, after it killed 5 patients. In this world, any tox, Grade 1 or above, earns patients a one-way trip to the hospital, which doesn’t come cheap. By avoiding tox, Juno hopes to prove that most patients can be treated in an outpatient setting, vastly reducing their overall cost — which some experts say may well range from $1 million to $1.5 million, all in.
It’s a compelling argument, and one that Juno has carefully crafted after one of the worst clinical setbacks in recent history. Their R&D work here will be carefully scrutinized at every step. To get on to the market, they’ll have to pass muster at the hands of a group of regulators embarrassed by their abrupt and inexplicable decision to lift the original hold on JCAR015 after just a few days — allowing more patients to die.
Juno has a high bar to clear, but they’re taking a running leap at it.
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