While visions of Thanksgiving turkey may still linger, the annual meeting for the American Society of Hematology (ASH) is just around the corner. Running from Dec. 3 through Dec. 6 in San Diego, ASH is always a key meeting for many of the companies involved in hematological cancers and hemoglobinopathies.
This year, data from many of the CAR-T developers will take center stage. Much of the data expected will help fill out the picture on earlier-stage pipeline assets, although Kite’s ZUMA-1 presentation on its lead therapy will draw many eyes.
Elsewhere companies like Spark Therapeutics and Celgene will present data on treatments in hemophilia and multiple myeloma, respectively. Check out the previews below for a quick guide on what to watch for as you plan your agenda.
Juno Therapeutics
Juno is on the defensive after disclosing two more patients died in its ROCKET trial after developing cerebral edema following treatment with JCAR015. With the study halted and new questions raised about JCAR015's toxicity, the path forward for the program has narrowed considerably. Company CEO Hans Bishop indicated discontinuing development could be one option.
Juno will likely give an update on its plans for JCAR015 at ASH and many in the sector will be watching to see the company's explanation for what went wrong. After three deaths in the same trial over the summer, Juno pinned the blame on the pre-conditioning agent fludarabine. But fludarabine was removed from treatment protocol in July and this time around company execs could only point to the "multifactoral" nature of side effects to CAR-T.
The company had already begun to focus more on its other pipeline assets before the new patient deaths, and many of the abstracts to be presented at ASH will focus on those products.
Treatment with JCAR017, a second-generation CAR-T, led to eight complete responses among 11 patients with DLBCL in a Phase 1 trial, according to one abstract. While the trial is early, Juno is encouraged by the relatively lower levels of toxicity observed. No patients in that study experienced severe cytokine release syndrome (CRS), a common side-effect of CAR-T treatment, and only two had dose-limiting neurotoxicity.
Juno plans to give an update on its overall plans for JCAR017 at ASH and hopes to push the treatment to market as soon as 2018 in non-Hodgkin lymphoma. Elsewhere, early data showed JCAR014 can be effective in treating chromic lymphocytic leukemia (CLL) in ibrutinib-refractory patients.
Kite Pharma
While the focus for Kite will be on its lead CAR-T therapy KTE-C19, crucial six-month follow-up data from the primary analysis of the ZUMA-1 study won’t be available until Q1 next year.
The California biopharma has already published topline interim results from the first 51 patients with 3 months of follow up, showing a third of patients experienced a complete response. Whether that response holds up over time will be a key question moving forward.
But the data released at ASH will do more to fill out the picture on treated patient characteristics, safety and one-month follow-up results from 42 more patients.
A late-breaking abstract on the diffuse large B-cell lymphoma (DLBCL) cohort of ZUMA-1 revealed progression-free survival at three months was 56% and disclosed that there was one treatment-related grade 5 adverse event.
Kite will also be discussing preliminary results from the ZUMA-3 and ZUMA-4 trials in acute lymphoblastic leukemia (ALL).
Novartis
The Swiss pharma will present interim data from a Phase 2 trial of its CAR-T therapy, CTL019, which will be included in a planned submission to the FDA in early 2017.
According to an abstract, 69% of CTL019-treated patients with relapsed or refractory ALL saw an objective response. High toxicity was observed but Novartis believes the rates of CRS seen are comparable to earlier studies.
Novartis recently decided to fold its dedicated cell therapy unit back into its broader organization, a move which CEO Joe Jimenez explained as motivated by preparing manufacturing capacity ahead of a potential launch. Questions still remain, however, if the move presages a retreat from the space after CTL019.
Bluebird Bio
Bluebird Bio was one of many biotechs which saw its stock crash after ASH abstracts were released November 3.
Shares in the Cambridge-based company fell by over 12% after abstracts showed mixed results from its Lentiglobin gene therapy, particularly in sickle cell disease (SCD).
While all seven SCD patients were successfully engrafted, treatment resulted in lower levels of therapeutic hemoglobin than expected.
However, Bluebird has since rolled out a new production process for inserting the targeted gene sequences into patient hematopoietic stem cells ex-vivo. This improved “process 2” will be used across the company’s late-stage studies in both beta thalassemia and SCD, but the updates at ASH will not feature any data from those studies.
Spark Therapeutics
Spark also suffered from a post-abstract drop hangover, as shares fell 16% in value November 3. But its stock has since roared back, rising nearly 40% in the three weeks since that low.
Investor concern was sparked by an immune response in one hemophilia B patient treated with SPK-9001, Spark’s experimental treatment for the bleeding disorder. The patient was placed on a tapering course of corticosteroids but didn’t experience any bleeds or need replacement clotting Factor IX.
Eight of the nine patients, excepting one with a suspected ankle bleed, did not experience any bleeding events.
Watch for further details on the one patient treated with steroids and look to see how Spark’s treatment stacks up to UniQure’s rival hemophilia B gene therapy.
Celgene
Revlimid, a blockbuster treatment for multiple myeloma (MM), has been Celgene’s main breadwinner for years and accounted for over 60% of net product sales last year.
So it’s fitting that much of Celgene’s presentations at ASH will focus on the blockbuster drug. Results from a 1550-patient Myeloma XI study demonstrated that the use of Revlimid in maintenance treatment of MM helped boost progression-free survival (PFS) in patients of all ages, according to one abstract.
Another scheduled oral presentation will detail the final analysis from the pivotal FIRST trial for transplant ineligible newly-diagnosed MM patients. Treatment with Revlimid improved both PFS and overall survival in that trial.
Analysts from Jefferies, expect the results further bolster the evidence base supporting continuous Revlimid use across settings.
Celgene filed an application with the FDA based on the FIRST results, with a decision on approval expected in early 2017.
Karyopharm
Small Newton, MA-based Karyopharm is pushing forward with development of its MM drug selinexor, broadening its development plans after positive results from the Phase 2b STORM trial.
At ASH, Karyopharm will present updated data from both the STORM trial and the Phase 1b/2 STOMP study.
In STORM, treatment with selinexor and low dose dexamethasone led to a 21% response rate among quad- and penta-refractory MM patients, a solid mark in such a heavily pretreated population.
STOMP, on the other hand, tested selinexor in combination with Takeda’s Velcade and showed a 58% response rate (7/12 patients) among refractory patients.
Karyopharm plans to expand the STORM study by adding 120 penta-refractory patients in an effort to support an accelerated approval with the FDA. Topline results from the expanded trial are expected in early 2018.
With future plans in place, presentations at ASH should give further clarity on how well selinexor stacks up against existing MM treatments in heavily refractory settings.