Juno Plunges After 3 Patients Die in Trial of Cancer Therapyby and
Shares decline by a record 27%, dragging down peers in U.S.
Drug developer has asked U.S. regulators to lift clinical hold
Juno Therapeutics Inc. plunged by a record 27 percent after three patients died in a trial for its lead cancer therapy and U.S. regulators put the study on hold, raising questions about the risks and tradeoffs of a new and very aggressive approach to treating cancer.
Two adult patients died last week after a chemotherapy drug called fludarabine was added to the treatment regimen for a therapy known as JCAR015, Seattle-based Juno said Thursday in a statement. Another patient, who also received the fludarabine pre-conditioning treatment, had died at the end of May. The treatment was being tested in adults with relapsed or refractory B-cell acute lymphoblastic leukemia, a cancer that affects the immune system.
Juno fell to $29.75 at 9:36 a.m. in New York on Friday. The news of the deaths dragged down the shares of other drugmakers making similar treatments.
All three patients died from swelling in the brains caused by excess fluids, Juno officials said on a conference call. When the first patient died in May, there were “confounding factors and a change in plans was not warranted,” Chief Executive Officer Hans Bishop said on the call. It was only after the two additional deaths last week that the U.S. Food and Drug Administration decided to stop the trial, according to the statement.
Acute lymphocytic leukemia is an aggressive blood cancer that progresses quickly without treatment. It is the most common type of cancer in children, who are often cured, according to the National Cancer Institute. Adults typically don’t do as well with ALL, which is diagnosed in 6,500 Americans each year and kills 1,430. In the study, the adult patients had failed to benefit from previous treatments, leaving them few options.
Juno is racing to be the first to market a novel type of cancer therapeutic called CAR-T, in which a patient’s immune system cells are removed, genetically engineered to recognize the cancer, and reinfused into the patient. The treatment was being tested in a study that was to enroll about 90 people, according to a U.S. trial registry.
Juno has enrolled more than 20 patients in the trial so far, and fewer than 10 have received the fludarabine pre-conditioning, according to spokesman Christopher Williams.
Juno has asked the FDA for permission to continue the trial without using fludarabine as part of the pre-conditioning treatment. The FDA has told Juno it needs to change its trial protocol, patient consent forms and information it provides to investigators, the company said. Juno plans to submit the information to the FDA this week.
Even if the FDA accepts the company’s proposals, it is unlikely to meet its goal of getting the therapy approved in 2017, Bishop said. Juno plans to update investors on its discussions with the agency during its earnings call in August.
The FDA declined to comment.
“Our program is on track and it is unaffected by today’s news,” David Chang, Kite’s chief medical officer, said in a phone interview. “We believe that we have done all the due diligence a company should do, including for the chemo-conditioning dose.”
Kite Chief Executive Officer Arie Belldegrun said the company has worked with the National Cancer Institute for 10 years, using that time to fine-tune details and reduce the risk of all aspects of the treatment before starting company-sponsored trials.
Kite investors shouldn’t be concerned about the Juno news because Kite uses a far lower amount of fludarabine in pre-conditioning patients in trials, according to Eric Schmidt, an analyst at Cowen & Co. who rates Kite shares outperform.
Kite “has a lot of data to support a low-dose regimen, which is safe and efficacious,” Schmidt said in a phone interview. “Comparing that to a high-dose regimen is apples to oranges.”
Benefits and Risks
Pharma giant Novartis AG uses fludarabine in its studies, said spokeswoman Julie Masow. “We have a positive benefit/risk profile," she said in an e-mail. Ziopharm CEO Laurence Cooper said his company isn’t affected because it doesn’t use a similar pre-conditioning regimen. Bluebird declined to comment.
Celgene Corp., which last year spent $1 billion to invest in Juno and join it in a 10-year CAR-T partnership, said after the announcement that it stands by the company. In April, Celgene said it would exercise an option to develop and commercialize Juno’s CD19 CAR-T program outside of North America and China. CD19 is a protein on cancer cells targeted by the Juno treatment.
“Celgene remains committed to Juno’s CD19 franchise and the potentially transformative impact of CAR-T therapy,” Greg Geissman, a Celgene spokesman, said in an e-mail.