Investigators working on Novartis' ($NVS) personalized CTL019 CAR-T program at the University of Pennsylvania say that 90% of a small group of children suffering from very advanced cases of treatment-resistant acute lymphoblastic leukemia achieved complete remission in the newly updated trial. With 78% of these kids alive 6 months after treatment, the physicians in charge say they're beginning to track some long-lasting results that underscore the therapeutic potential for this therapy, which is now in Phase II and may be ready for regulators as early as 2016.
"We have been amazed how well that has been working," says Stephan Grupp, a professor of pediatrics in Penn's Perelman School of Medicine.
The Novartis-backed effort turned early to the pediatric population, and now Grupp says that investigators are able to report some long-term effects, with one child being treated for 2.5 years.
"That's a first," says Grupp, adding that these responses in a clinical trial are "unprecedented."
CTL019 is a new therapy that is made by extracting T cells from patients and arming them with chimeric antigen receptors, which essentially trains the immune system's foot soldiers to track down and kill tumor cells. Novartis has been financing an ambitious effort to accelerate these treatments as fast as possible in the hope of gaining some quick approvals for what promises to be a revolutionary advance in cancer therapy.
The FDA has also provided "breakthrough" status for the treatment, which should help shorten the amount of time it will take to gain an approval.
In addition to the effort at Penn, Juno in Seattle and other players like Kite ($KITE) and bluebird ($BLUE) have been ramping up their own efforts. But CAR-T treatments aren't without risk. Eight of the children in this study experienced a cytokine storm that was so severe they had to be hospitalized. But they all recovered.
"Everybody gets some kind of CRS" reaction, says Grupp, and a third of them end up in the ICU with serious reactions. But investigators have also learned that by blocking IL-6 with the immunosuppressant tocilizumab, they can often prevent the worst reactions. Another key lesson emerging from the study: The toxicity reflected in the data is directly linked to the disease burden. The lower the disease burden, the lower the odds for a serious reaction, which bodes well for patients once the treatment is used in less advanced patient groups.
The next step, says Grupp, is to focus on the Phase II study, which includes 8 or 9 centers around the country. "We have to show that other centers can do this," he says. And then Novartis says it could be able to file for an approval around the 2016 time frame.
The research group says it now has a half-dozen other CAR trials open, including a newly launched glioblastoma study targeting EGFR, and the multicenter ALL trials--for both pediatric patients and adults--are on track to open this fall. Plans are also now set for the construction of the Penn-Novartis Center for Advanced Cellular Therapeutics, a $20 million facility being funded by Novartis.
- here's the release