Key Takeaways and Learnings from ASH 2023

Published January 12, 2024

Introduction

The Trinity Life Sciences’ team recently attended the 65th ASH Annual Meeting and Exposition from December 9-12, 2023, in San Diego, California. The conference brought together physicians, scientists and industry experts to share and collaborate on advances in understanding and treating blood cancers and blood disorders. Below are a few of the key insights that the Trinity team observed during the conference:

Advances in CAR-T Therapy: Expansion into New Targets and Therapeutic Areas

Numerous groups across the industry are attempting to build upon the success of currently approved CAR-Ts in hematological malignancies with their own next-generation approaches. Galapagos presented updated data for its CAR-Ts, manufactured using a proprietary point-of-care model with an impressive seven-day turnaround time, showing response rates in line with YESCARTA® in Non-Hodgkins Lymphoma and above BREYANZI® in Chronic Lymphocytic Leukemia. In Multiple Myeloma, Gracell’s BCMA/CD19 dual-targeting CAR-T and ArcellX’s anito-cel (ddBCMA CAR-T) demonstrated potentially highly competitive efficacy. Beyond oncology, encouraging findings presented by the Mueller group from the Bavarian Cancer Research Institute suggest CAR-T potential could extend into autoimmune conditions. All of the study participants, 15 heavily pre-treated patients with autoimmune diseases (systemic lupus erythematosus, idiopathic inflammatory myositis and systemic sclerosis), remained in remission 15 months post treatment with the CD19-targeted cells.

Innovations in the CAR-T space have the potential to dethrone current blockbusters in oncology and provide an effective therapeutic option to patients in additional disease areas with high unmet need.

Excitement in Sickle Cell Disease: Simultaneous Approval of Two Gene Therapies

The recent FDA approval of two gene therapies for Sickle Cell Disease has generated a palpable sense of enthusiasm in the medical community, which was evident at ASH. CASGEVY™, developed by Vertex and CRISPR Therapeutics, uses CRISPR technology to edit blood stem cells and increase the production of fetal hemoglobin, while LYFGENIA™ from Bluebird Bio introduces genetic modifications into the patient’s blood stem cells to produce a type of hemoglobin A.

On the heels of these historic approvals, other companies utilized ASH to highlight progress in Sickle Cell Disease. Of note, Editas shared promising results in a small group of patients for its gene therapy (also CRISPR technology), Kamau Therapeutics presented extended follow-up data on the first patient dosed with its therapy and announced plans to treat the next patient by the end of 2024 or early 2025, and Pfizer presented data for its next-generation sickle cell medicine, GBT601, and hinted at plans for a registrational study.

While competition in the market is increasing, the development of these new therapies offers hope for patients with sickle cell disease and the potential for improved treatment outcomes.

Fight for Myelofibrosis: AbbVie’s Navitoclax vs MorphoSys’ Pelabresib

JAKAFI®, a janus kinase inhibitor (JAKi), has long been the front-line standard of care for patients suffering from myelofibrosis (MF), a hematologic malignancy associated with splenomegaly, bone marrow fibrosis and anemia. While recent approvals of non-myelosuppressive JAK inhibitors may end up shifting the paradigm given their ability to address anemia (a key manifestation of MF), there are two key players with late-stage assets seeking to build off the longstanding JAKAFKI® monotherapy standard of care in 1L with combination regimens: AbbVie’s Navitoclax and MorphoSys’ Pelabresib. Both companies released phase III data, from their TRANSFORM-1 and MANIFEST-2 trials, respectively, at well attended sessions during this year’s ASH conference. And while both products demonstrated statistically significant improvement in their primary endpoint of spleen volume reduction (SVR) at 24 weeks, they each failed to meet their secondary endpoint of total symptom score (TSS) improvement, likely signaling the high bar to improve upon JAKAFI®. Given the established link between SVR and overall survival (OS), both KOLs and management at each company remain optimistic about approval and subsequent uptake. However, regulatory approval is not necessarily guaranteed, given existing FDA precedent requiring statistically significant TSS improvement. Based on positive trends in that endpoint, and in terms of key adverse events like thrombocytopenia, pelabresib seems to hold a slight edge in this head-to-head battle.

With limited existing options and poor prognoses for MF patients to date, novel approaches like these have generated optimism among both treaters and patients alike and could begin to move MF treatment toward the combination-heavy front-line regimens that are characteristic of other hematologic malignancies.

Conclusion

From incremental advancements brought by conventional therapies in high unmet need diseases to breakthrough developments with cutting-edge genomic medicines, there is a lot of progress to celebrate this year and even more to look forward to next winter for the 66th ASH Annual Meeting back in San Diego, California.

Authors: Nikki Aaron, Jake McIntyre and Keya Viswanathan