With cancer immunotherapy tallying impressive patient results and new drug approvals, people in the field are confident about expanding its scope. That confidence was abundant in back-to-back presentations Sunday at the American Society of Hematology annual meeting before an audience into the thousands.
Two heavyweights in cancer immunotherapy, Carl June, a professor at the University of Pennsylvania, and Steve Rosenberg, chief of surgery at the U.S. National Cancer Institute in Bethesda, MD, fleshed out some of the more recent developments in the field and provided insight into where the companies associated with their work might be headed.
June went first, but Rosenberg best encapsulated the dizziness of the pace of progress and the broad scope of expertise needed to grasp its potential. “Here you have a surgeon talking to hematologists about immunology,” Rosenberg said with a laugh to kick off his talk. “It doesn’t make a lot of sense.”
The audience was there to hear about a particular kind of cancer immunotherapy, in which a patient’s own T cells are extracted, genetically engineered, grown to numbers in the billions, then given back to the patient with a new protein that helps them zero in on cancer cells and kill them. There are two main types in development. “I believe both will be approved in the next several years,” said June.
June’s lab work is behind a program, CTL019, to which drug firm Novartis (NYSE: [[ticker:NVS]]) took exclusive license in a 2012 deal. (June has also worked on cell-based therapy for HIV.)
He stressed the safety of not only CTL109, which has been administered to more than 135 patients, but all programs based on T cell reengineering. In more than 1,000 “patient-years,” he said, there have been no long-term adverse effects.
The growing body of evidence from June and his peers is showing that reengineered T cells are attacking cancers quickly, then staying alive in the body to do their work. “They’re a living drug, they replicate and they persist for decades,” June said.
There have been serious side effects upon treatment, including an overdrive of the immune system called cytokine release syndrome that immunotherapies can provoke.
But the more practice oncologists have with immunotherapies, the more understanding of the underlying biology will provide strategies to deflect the side effects. At least that’s the hope. For example, investigators have seen a correlation between the amount of tumor a patient has (in blood cancers, this is often measured by the cancerous cells crowding out healthy ones in the bone marrow) and his or her susceptibility to cytokine storms, as the release syndrome is sometimes called. Identifying those patients and optimizing their doses will be important counter-strategies, said Juno Therapeutics CEO Hans Bishop. Juno, a key player in T cell therapy development and an IPO hopeful, did not participate in the ASH symposium, but Bishop and CFO Steve Harr spoke with Xconomy afterwards.
They concurred with June and Rosenberg that oncologists and developers also have pharmaceutical tools to combat side effects. Some cytokine release cases are treatable with steroids, others with the anti-inflammatory antibody tocilizumab (Actemra). Despite concern about cytokine release syndrome, the FDA sped up its typical review period and last week approved blinatumumab (Blincyto) from Amgen (NASDAQ: [[ticker:AMGN]]), albeit with a special warning and mandatory program to closely follow side effects.
Blinatumumab is an example of the other major type of cancer immunotherapy: monoclonal antibodies that engage the immune system. Some remove immune “checkpoints” that tumor cells exploit to hide from detection. Ipilumumab (Yervoy) from Bristol-Myers Squibb (NYSE: [[ticker:BMY]]) was the first, approved in 2011, and more recently was pembrolizumab (Keytruda) from Merck (NYSE: [[ticker:MRK]]). Blinatumumab works in a different way, using two different receptors to grab T cells and “recruit” them to attack malignant B cells in a rare form of acute lymphoblastic leukemia.
“People should cheer the FDA,” said Bishop. “These patients have got a terrible prognosis and the speed at which the FDA approved blinatumumab recognizes that unmet need.”
Blinatumumab’s approval was significant not just for its speed—FDA said yes based on Phase 2 data in 185 patients, 41.6 percent of whom had complete remission of their disease—but also because blinatumumab attacks tumor cells that feature the protein CD19 on their surface.
That adds an interesting wrinkle to the cancer immunotherapy race, because CD19 is also the target for most of the cell-based therapies, known as CAR or CART, now being tested in clinical trials—including the Penn-Novartis collaboration CTL019.
“We believe CAR cells can work in patients who become
