Data Roundup: February 2024 Features Updates in Blood Cancers, Lysosomal Storage Disorders at WorldSymposium, Tandem Meetings

Last month, February 2024, the CGTLive® team was diligently tracking the latest data readouts and published literature on cell and gene therapies within oncology, ophthalmology, and rare diseases.

As more and more innovative therapies enter the clinical trial field, more data is accrued every month, buoying excitement in the field and sometimes making or breaking the fates of small biotech companies. Last month delivered promising data updates presented at the 2024 WORLDSymposium and 2024 Tandem Meetings |Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR, for multiple therapies treating lysosomal storage diseases and multiple treating hematological malignancies. Our team has highlighted these and other updates below.

Click the read more buttons for more details and information about each update.

4D Molecular Therapeutics’ Wet AMD Gene Therapy 4D-150 Reduces Need for antiVEGF Injections in Interim Phase 2 Trial Data

February 4, 2024 - 4D Molecular Therapeutics’ 4D-150, an investigational dual-mechanism gene therapy being evaluated for the treatment of wet age-related macular degeneration (AMD) in the phase 1/2 PRISM clinical trial (NCT05197270), has continued to demonstrate the ability to reduce the need for antivascular endothelial growth factor (VEGF) injections in newly announced interim data.

“[The] majority of the patients need frequent injections—and that's the biggest unmet need, where the treatment burden is so high for many of these patients that they don't get the adequate number of injections that they need. And that's why in [the] real world, we see visual acuity outcomes that are worse than what we see in clinical trials. So there is really an unmet need for having durable agents and sustained delivery of anti-VEGF. Gene therapy is one modality to address this treatment burden and hopefully stabilize visual acuity and improve long-term outcomes in the real world,” investigator Arshad Khanani, MD, the director of clinical research and director of Fellowship at Sierra Eye Associates, told CGTLive.

At the 24-week analysis, patients who received the high dose achieved an 89% decrease in annualized antiVEGF injection rates and patients who received the low dose achieved an 85% decrease in annualized antiVEGF injection rates. Patients who received the high dose showed a –1.8 change in Early Treatment Diabetic Retinopathy Study (ETDRS) letters for BCVA and patients who received the low dose showed a +1.8 change in ETDRS letters for BCVA. For CST, patients in the high dose arm showed a –8.3 µm change and patients in the low dose arm showed a +29.9 µm change.

UX111 Reduces Heparin Sulfate, Correlating With Benefit in Cognitive Function in Pediatric MPSIIIA

February 28, 2024 - UX111 gene therapy reduced heparin sulfate (HS) exposure in the cerebrospinal fluid (CSF), which correlated with stabilized or improved cognitive function in patients with mucopolysaccharidosis type IIIA (MPSIIIA), also known as Sanfilippo syndrome.

“By clearing out that toxic accumulation of heparin sulfate, over the long term, we're starting to see a benefit in the overall cognition of children. There's also additional data that we're looking at that's showing preliminarily an impact on language, both expressive and receptive. So overall, we are showing initially positive results on the neurodevelopment of children with MPSIIIA,” Heather Lau, MD, MS, executive director, global clinical development, Ultragenyx, who presented the data at WORLDSymposium, told CGTLive.

The investigators found that mean CSF HS decreased 58.5% (SD, 13.8%) from baseline at month 1. At the last follow-up, with a data cutoff date of August 16, 2023, CSF HS exposure was reduced by a mean 63.3% (95% CI, 56.9-69.7). Treatment with UX111 also led to reductions in CSF gangliosides, including GM2 and GM3, and stabilized total cortical volume on brain MRI to within normal limits.

Orchard Therapeutics’ Arsa-cel Restores ARSA Enzyme Activity in Patients With Late Juvenile MLD

February 9, 2024 - Orchard Therapeutics’ atidarsagene autotemcel (arsa-cel, also referred to as OTL-200 and approved as Libmeldy in the European Union, UK, Iceland, Liechtenstein, and Norway), a gene-edited cell therapy intended to treat metachromatic leukodystrophy (MLD), has enabled restoration of arylsulfatase A (ARSA) enzyme activity among patients with the late juvenile (LJ) form of MLD.

“Initial results show pharmacodynamics efficacy with stable levels of gene-corrected cells as well as reconstitution of ARSA activity to normal or supranormal levels both in peripheral blood and CSF in LJ MLD patients, comparable to those observed in other patients with early-onset MLD treated in the clinical development program,” first author Vera Gallo, MD, staff pediatrician, San Raffaele Telethon Institute for Gene Therapy, and colleagues concluded in their WORLDSymposium poster.

Time to neutrophil engraftment ranged from 26 to 42 days (median, 33) posttreatment and time to platelet engraftment ranged from 25 to 46 days (median, 26) posttreatment. Furthermore, in the peripheral blood mononuclear cells (PBMCs) and in CD15+ cells ARSA activity reached supranormal levels. In 3 patients for whom central nervous system pharmacodynamic efficacy measures were available, ARSA activity in the cerebrospinal fluid (CSF) increased to normal levels.

Immune Effector Cell Therapy Associated With Longer PFS After Ide-Cel Relapse in R/R MM

February 22, 2024 - Immune effector cell (IEC) therapies were associated with better median progression free survival (PFS) in patients with multiple myeloma (MM) than non-IEC therapies even immediately after idecabtagene vicleucel (ide-cel, Abecma; Bristol Myers Squibb, 2seventybio) therapy and should be the first choice of treatment if available.

“With the availabilities of immune effector therapies, after failure of immune effector therapy, what is the best therapy? What are the concerns for giving back-to-back immune effector therapies? The first one is B-cell exhaustion; the second one is, postimmune effector therapy, depending on the timing of relapse, lymphopenias or cytopenias can either preclude collection or subsequent immune effector therapy; and the third one has been infections,” Murali Janakiram, MD, MS, Associate Professor, Department of Hematology & Hematopoietic Cell Transplantation, City of Hope, said during his presentation at Tandem 2024.

In looking at IEC compared with non-IEC therapy, investigators found that ORR was 38% compared with 22.3% (P = .1) in first relapse and 21% compared with 29.5% (P = .69) Median PFS was 106 days compared with 66 days (P = .004) in first relapse and 66 days compared with 44 days (P = .3) in second relapse.

LV20.19 CAR T-Cells Show Efficacy in CLL, Richter, But Unusual Rates of IEC-HS

February 24, 2024 - LV20.19 chimeric antigen receptor (CAR) T-cells were efficacious in treating chronic lymphocytic leukemia (CLL) and Richter transformation (RT) but patients experienced dose-limiting toxicities and high rates of immune effector cell hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS).

“Thinking about CLL, there are no approved products, although we anticipate some in the future, for either CLL or something specific to RT,” Nirav N. Shah, MD, associate professor, Medical College of Wisconsin, said during his presentation at Tandem 2024. “Moreso, we think of CLL as being a CD20–dim histology, but recent studies have shown that drugs like obinutuzumabdo have clinical benefit and do target the CD20 protein on B-cells.”

The investigators found that 16 of 17 (94%) patients developed cytokine release syndrome (CRS), 2 of which, with CLL, had grade 3 CRS. Most cases required tocilizumab (93%). Three patients developed immune effector cell-associated neurotoxicity syndrome (ICANS; 18%): 2 patients with CLL developed grade 3 and 4 ICANS (the latter was found to have CLL involvement in the CS.