[Corrected 3/1/17 to update trial data] Juno Therapeutics is still mulling next steps for its lead product, an experimental cancer immunotherapy now stuck in limbo. Five of 38 adult leukemia patients taking the product in a clinical trial called “Rocket” have died from severe brain swelling caused by the treatment.
In an after-dinner review at the American Society for Hematology conference in San Diego, however, company executives spent most of their time touting other products in their pipeline for other cancers, in what sounded like the first step of a sharp pivot.
Juno (NASDAQ: JUNO) officials certainly acknowledged the serious matter of the patient deaths. CEO Hans Bishop called the five deaths an “unacceptable risk-benefit” ratio and admitted the company doesn’t know what caused them. When the first three deaths occurred—Juno reported them in July, leading the FDA to suspend the study—executives blamed one of the two chemotherapies used to prepare patients for the main JCAR015 treatment: the patient’s own T cells, engineered to be better cancer fighters outside the body, then reintroduced into the patient. (The patients all had acute lymphoblastic leukemia, or ALL, and had failed other therapies.)
But two more people died of the same brain swelling after Juno took out the suspected chemotherapy and resumed the trial with the FDA’s blessing. Reporting the additional two deaths the day before Thanksgiving, Juno said it would halt the trial again.
Juno has three options for JCAR015 in adult ALL, Bishop said: Modify it. Start anew with a different design. Or shut it down completely.
Meanwhile, two rivals plan to ask the FDA early next year to consider their CAR-T therapy for approval. Novartis (NYSE: NVS) wants the green light to treat kids with ALL, and Kite Pharma (NASDAQ: KITE) has begun a “rolling” application for FDA approval in non-Hodgkin lymphoma (NHL).
The backdrop of Kite’s timeline seemed to add weight to comments Juno officials made Monday evening. With Rocket shelved, Juno is back to building evidence for treatments that have only been tested in a couple dozen people at most. Juno executives touted their own NHL treatment, which is not as far along as Kite, by emphasizing the unusual advanced age and frailty of the patients in their trial, dubbed Transcend. It was a recap of data released earlier that day by an academic collaborator, but it was also a positioning exercise to suggest that the product, dubbed JCAR017, might be able to treat NHL patients who might not be able to handle other CAR-T therapies or “be eligible for aggressive therapies,” said chief medical officer Mark Gilbert.
Among other factors, Gilbert touted the relatively low doses in the trial that have so far seemed quite effective. Of 20 patients whose response could be measured, 12 had complete remissions. Three of 22 patients had serious neurological side effects, treated with steroids, and one had the immune reaction known as cytokine release syndrome. All the patients were treated with the same chemo combination that the JCAR015 patients received before the first hold on the Rocket trial.
Gilbert said the plan was to move JCAR017 next year into a pivotal study in NHL—one designed to present regulators with data for commercial approval. Still, it’ll take time for Juno to convince investors of JCAR017’s potential. In a research note Tuesday morning, RBC Capital Markets’ Michael Yee said the data were “not too overly impressive” and did not appear to be drastically different than Kite’s KTE-C19 at this point.
In another type of blood cancer, chronic lymphocytic leukemia (CLL), Gilbert targeted 2019 as the goal for regulatory approval, also with JCAR017. Juno’s academic collaborator Cameron Turtle, a researcher at the Fred Hutchinson Cancer Research Center in Seattle, has been testing CLL patients who had not responded well to the standard of care, a drug called ibrutinib (Imbruvica). Turtle reported this weekend that 7 of 14 patients in his study to get another Juno product, JCAR014, have had no sign of cancer in their bone marrow after one month measured by a more sensitive sequencing technique. All seven remained disease free, ranging from three to 26 months after treatment. One patient in the study died, however, after severe brain swelling and cytokine release syndrome. The 24 CLL patients had a total of eight serious side effects.
The side effects and death are an obvious caveat in light of Juno’s inability to explain the Rocket deaths. The small sample size for the positive responses is another caveat. Yet another is that Juno doesn’t plan to carry forward JCAR014 commercially. It has the same technical underpinnings as JCAR017, but any major study aimed at approval would have to use JCAR017.
Juno chief scientific officer Hy Levitsky also outlined Juno’s plans to go after multiple myeloma, a cancer of the bone marrow’s plasma cells, which other T cell developers have also begun to tackle. A first spate of human studies in recent months, culminating with data that Bluebird Bio (NASDAQ: BLUE) released last week, has created a “competitive landscape,” Levitsky said. The target of choice so far is BCMA, a protein that cancerous plasma cells display on their surface. Juno wants to follow suit with its own BCMA-targeting CAR T cells in the first half of next year, Levitsky said. But Juno also has two other targets in mind for myeloma, which it isn’t disclosing for now, he said.
Image of healthy T cell courtesy of NIAID via Creative Commons.