(Reuters) - A promising but risky new group of customized cancer drugs will be in focus this weekend at the annual meeting of the American Society of Hematology (ASH), where clinical trial results will help clarify their potential for doctors and investors.
Experimental chimeric antigen receptor T-cells, or CAR-Ts, are made by genetically altering a patients' own T-cells in the lab to help the immune system find and kill cancer cells. The altered cells are then infused back into the patient.
Early excitement over the drugs has propelled investor interest in biotech Kite Pharma Inc, whose shares have tripled since a 2014 initial public offering, as well as rival Juno Therapeutics Inc, whose therapy JCAR015 has generated concerns after five leukemia patients died due to severe brain swelling. Juno shares now trade about 14 percent below their IPO price.
"Juno has dug themselves into such a deep hole," said Brad Loncar, manager of the Loncar Cancer Immunotherapy ETF. "My guess is that they may drop the JCAR015 program." He will be watching closely to see whether data at ASH on another Juno candidate, JCAR017, shows similar issues.
Data on CAR-T drugs from Kite and Novartis AG will also be presented at the meeting.
In early trials, CAR-Ts eliminated all trace of leukemia and lymphoma in 40 percent to 90 percent of patients who had run out of other options. But it is not yet clear how long those remissions will last. Also, the drugs can overestimate the immune system, which can cause dangerous side effects.
If they work safely, Wall Street expects annual sales for CAR-T therapies in the billions of dollars.
Shares of Bluebird Bio Inc closed 14 percent higher on Thursday after a small study showed that its CAR-T, bb2121, induced remission in several patients with advanced multiple myeloma with no worrisome side effects. The Bluebird drug is being developed in partnership with Celgene Inc.
"The data look good, but these are very small trials," said Les Funtleyder, healthcare portfolio manager at E Squared Asset Management in New York, which does not currently hold positions in CAR-T companies. "We would definitely like to see larger sample sizes and longer duration." He is also looking for clarity on pricing. Estimates have run into hundreds of thousands of dollars per treatment. It is not yet clear if patients will need more than one treatment or whether that can even be done safely.
The CAR-T technique is being tried initially against blood cancers, which contain specific proteins that can be differentiated from normal tissue, limiting a possible immune system attack on healthy organs. Drugs like Juno’s JCAR015 target a protein called CD19, which is found on the surface of a type of white blood cell.
Juno is slated to present early-stage data at the ASH meeting in San Diego on JCAR017, which also targets CD19.
Juno Chief Executive Hans Bishop said JCAR017, and the similar JCAR014, are safer than JCAR015 because of a manufacturing process that allows for active control of the composition of the T-cells that make up the final product, said
"We think when you get to the extremes ... that is likely a source of variability," he said.
Novartis plans to file next year for U.S. Food and Drug Administration approval for its drug, CTL019, in children with acute lymphoblastic leukemia who have exhausted other options, based on Phase 2 trial results to be released at ASH on Saturday.
The study results show "what it looks like when you roll this out to a bunch of different centers across the world," said Dr Stephan Grupp, research director at Children's Hospital of Philadelphia's childhood cancer center and the study's lead investigator.
He said most patients in the Novartis trial experienced a serious side effect known as cytokine release syndrome, or CRS, as well as neurological toxicity, including confusion and seizures, but all responded to treatment for those side effects and none had severe brain swelling.
Kite is expected to report further details from a Phase 2 trial of patients with an aggressive type of lymphoma whose cancer returned despite treatment with chemotherapy or a bone marrow transplant. Interim results showed that a month after treatment 47 percent of patients achieved complete remission, but that rate dropped to 33 percent after three months. The company, which said it will begin a rolling FDA application, expects to have data with six months of follow-up in the first quarter of next year.
"These are the first results from a large multi-center trial," Jeff Wiezorek, head of clinical development at Kite, told Reuters. "The safety and efficacy look similar to what we saw in smaller trials."
(Corrects to Juno candidate JCAR017 instead of Kite, paragraph 4)
Reporting By Deena Beasley; Editing by David Gregorio