Novartis has decided to dissolve its group that has been working on a cutting-edge therapy to treat cancer. In an internal email obtained by Endpoints, the head of the healthcare giant’s cell and gene therapies unit, Usman “Oz” Azam told the group that “things don’t always work out as envisioned.”
Novartis spokeswoman Julie Masow confirmed to Xconomy the end of the group, calling it an “internal re-alignment,” with 120 positions eliminated and others spread around to other divisions. But the healthcare giant also says it remains committed to cell and gene therapies and will move forward with its most advanced product, CTL019, an experimental cancer immunotherapy that uses a patient’s own immune cells. It came from Novartis’s long-term R&D tie-up with the University of Pennsylvania.
Novartis still plans to ask U.S. and European regulators for approval next year, as a treatment for children with dire cases of the blood cancer acute lymphoblastic leukemia (ALL), assuming current trials go well. At last update, in December, 93 percent of patients (55 of 59) had seen their cancers disappear during treatment with CTL019, but in a good portion of them, the cancer returned within a year. (Relapse-free survival was 55 percent after 12 months.) Those data were from Penn. Novartis has since expanded the trial worldwide.
Competitors Kite Pharma (NASDAQ: KITE) and Juno Therapeutics (NASDAQ: JUNO) are developing similar products: engineered immune cells, called chimeric antigen receptor or CAR-T cells, that are drawn from a cancer patient’s own body and modified to attack blood cancers. Both saw their stock fall Wednesday. An index of cancer immunotherapy stocks, which includes CAR-T cell developers, ended the day down 1.5 percent.
RBC Capital Markets biotech analyst Michael Yee wrote in a note to investors that Novartis’s move isn’t necessarily a sign that the entire field of engineered T cells to fight cancer has hit headwinds. “Re-organizing and re-structuring divisions sounds pretty typical and regular for big pharma’s broader bureaucracy,” Yee wrote.
That’s not to say the CAR-T field hasn’t encountered problems. Juno’s JCAR015 recently encountered a “speed bump,” as chief financial officer Steve Harr called it: the deaths of three adult ALL patients that the company reported in July. Juno blamed a chemotherapy combination used to weaken the cancer in preparation for the T cell treatment. The FDA allowed Juno to continue the trial after the company decided to eliminate one of the chemotherapies from the mix.
In an interview with Xconomy, Harr said that Juno’s other T cell products, all experimental as well, will continue with the chemo combination. This sort of “preconditioning,” as the practice is called, will be standard for the foreseeable future, he said.
That’s one way in which the early promise of T cell therapy has come down to Earth, in a sense: that blunter instruments like chemotherapy, which doctors and patients would love to move away from, remain key to making T cell therapies work.
Another challenge in the T cell field is the difficulty moving beyond a small group of blood cancers. Fighting other blood cancers, as well as solid tumors which represent the vast majority of cancer cases, has been a harder code to crack, although first attempts at clinical testing are abundant. Novartis collaborator Carl June, an immunology specialist at Penn, coauthored a paper published last week that underlined the difficulty with solid tumors, which tend to have better weapons to evade the immune system and pose more safety risks because the proteins they display on their surfaces, and which T cells would attack, can also be abundant in healthy tissue.
Spokeswoman Masow noted that Novartis is pressing ahead with trials to treat diffuse large B-cell lymphoma with plans to file for regulatory approval next year. But one question, yet to be answered, is how intensively Novartis will push some of its other CAR-T programs.
Juno’s Harr declined to speculate on Novartis’s motivations but said the T cell space “requires risk tolerance and is expensive.” Novartis, Juno, Kite, and their academic partners have all reported early spectacular results in people with types of leukemia and lymphoma, all focusing on one protein, CD19, that those cancer cells produce. Given the similar good results, Harr said Juno has also invested heavily in manufacturing and automation, with the belief that it will produce cheaper, more consistent products if and when their treatments come to market.
For products like Novartis’s CTL019 and Juno’s JCAR015, T cells will have to be extracted from a patient, engineered outside the body to better recognize and attack cancer, and reintroduced back into the patient—a complicated process with live biological material. Novartis bought a manufacturing plant in New Jersey a few years ago from Dendreon, a failing cell-therapy developer, for $43 million. More recently it cofounded an R&D center in Philadelphia with Penn. Novartis kicked in $20 million, according to the university.
Image of healthy T cell courtesy of NIAID via Creative Commons license.