[Editor’s note: Deputy Biotechnology Editor Ben Fidler co-wrote this story.] The annual American Society for Hematology meeting, held this year in Orlando, FL, ends today. The meeting is a showcase for new data, drugs, and approaches to treat cancers like leukemia, rare genetic diseases, and other maladies that originate in or otherwise affect blood.
But ASH also highlights lessons in investor psychology. Last year, at the conference in San Francisco, strong early data in new treatments for blood cancers and beta thalassemia helped buoy an already bullish market for biotech.
This year, biotech markets are depressed, and investors are in no mood to see glasses half full, punishing companies for not meeting unrealistic expectations, or, it seems, for just being biotech companies. On Monday, the biotech indices fell two to three percent, before recovering a bit this morning.
One problem: programs that showed great early data in 2014 are a year older, with more patients to deepen the sample size. Inevitably, some of those programs would come back to Earth—the same way a baseball player who has a hit in every two April at-bats isn’t going to stay at .500 all year.
In this roundup, we highlight the big ASH moments of the past three days and provide context for new developments regarding some of the most important technologies and blood diseases.
CAR-T immunotherapy
A huge driver for biotech enthusiasm in 2014 and much of this year were early results in new therapies called CAR-T—chimeric antigen receptor T cell—that use modified T cells to attack a patient’s cancer.
One month ago, an ASH abstract revealed that a CAR-T therapy helped beat back the leukemia of a British infant who was at death’s door. The intervention came as a special request by the parents, not as part of a clinical trial, but the therapy, UCART19, developed by French firm Cellectis (NASDAQ: [[ticker:CLLS]]), should enter testing soon in the hands of Cellectis’s bigger partners Servier and Pfizer.
(The doctors who gave UCART19 to the young girl were scheduled to present their case study at ASH Saturday, but there was no news coverage.)
UCART19 is an allogeneic or “off the shelf” T cell therapy, which means the T cells were extracted from donors, modified in a lab, and given to the patient. To avoid an immune mismatch, which could kill the recipient, and add other functions, UCART19 includes T cells whose DNA is edited three different ways, the first use of a gene edited cell to treat cancer.
But most of the past year’s good news for CAR-T came in Phase 1 trials from autologous, or personalized programs in which the T cells are collected directly from a patient. They were run by or licensed to Kite Pharma (NASDAQ: [[ticker:KITE]]), Novartis (NYSE: [[ticker:NVS]]), and Juno Therapeutics (NASDAQ: [[ticker:JUNO]]). In a trial run by Juno’s partner Seattle Children’s Hospital, for instance, 20 of 22 children had their acute lymphoblastic leukemia go into complete remission.
That was the spring. Monday, despite releasing fairly positive news, Juno shares took a tumble of more than 7 percent, or $3.79, even though its academic collaborators continued to show large majorities of patients with desperate cancers having positive responses to its modified T cell therapies.
The big difference between ASH 2015 and 2014 for Juno: a declaration from the company that patients with blood-borne cancers would get a powerful combination of chemotherapy drugs to bash the cancer—“preconditioning” is the medical term—before unleashing Juno’s cancer-killing T cells. Preconditioning has been studied for a while with T cell therapy; this small American-Swedish joint study drew some attention earlier this year.
But Phase 1 trials, run by Juno collaborator Cameron Turtle of the Fred Hutchinson Cancer Research Center in Seattle, showed patients with non-Hodgkin lymphoma and chronic lymphocytic leukemia fared better when receiving fludarabine and cyclophosphamide, two chemotherapy drugs, before the JCAR014 T cell therapy.
Juno chief financial officer Steve Harr told Xconomy the double dose of chemo would be applied “broadly across our portfolio, at least in [hematological] malignancies.”
“I do not want to minimize the chemo, but it is generally a single course and well tolerated,” Harr wrote in an e-mail. “It is something that we want to work to eliminate over time, but [we] do not see it limiting us, at least in the patients we are treating today.”
Harr said Juno is also evaluating the impact of the chemo combination on patients in the 90-person Phase 2 trial it recently began with JCAR015, another one of its cell therapies, in adults with acute lymphoblastic leukemia. Juno hopes to use that JCAR015 trial data to ask the FDA for marketing approval.
The only CAR-T program ahead of Juno’s JCAR015 is from Novartis, which nabbed the University of Pennsylvania as its exclusive partner in 2012 and touched off the stampede into the area. At this year’s ASH, Novartis became the first to report Phase 2 CAR-T data, from its CTL019 treatment for patients with certain relapsed or refractory non-Hodgkins lymphoma (NHL). Three months after treatment, 15 of 26 patients across two subtypes of NHL showed some kind of response. Six of them had a partial response that became a complete response—no sign of cancer—at the six-month mark. Two other patients went backwards, with their
