Data Roundup: January 2024 Features Updates in GI Cancer, AMD, Neurology

Last month, January 2024, the CGTLive™ team was diligently tracking the latest data readouts and published literature on cell and gene therapies within oncology, neurology, 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 updates for multiple therapies treating neurological diseases, including AskBio’s gene therapy for Parkinson disease, Neurona’s cell therapy for epilepsy, and Passage Bio’s gene therapy for frontotemporal dementia. Our team has highlighted these and other updates below.

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

Satri-Cel Shows Some Disease Control in Gastric/Gastroesophageal and Pancreatic Cancer

January 19, 2024 - Satricabtagene autoleucel (satri-cel; CT041; CARsgen) chimeric antigen receptor (CAR) T-cell therapy has shown some efficacy in patients with heavily pretreated CLDN18.2-positive advanced gastric/gastroesophageal (GC/GEJ) or pancreatic cancer (PC) treated in cohort A of the phase 1b ELIMYN18.2 clinical trial (NCT04404595).1

“Satri-cel’s, the first autologous CLDN18.2 CAR T cell therapy, safety profile was encouraging, with manageable treatment-related AEs. Initial efficacy was promising in heavily pretreated CLDN18.2-positive advanced GC/GEJ and PC population and consistent with earlier reports. DL3 (600x106 cells) was selected as RP2D and enrollment in phase 2 is currently ongoing,” Gregory P. Botta, MD, PhD, associate professor of medicine, University of California San Diego, and colleagues wrote in their poster for the 2024 ASCO GI symposium.

Investigators found that the safety profile of satri-cel was manageable, although all patients had at least grade 3 treatment-emergent adverse events (AEs) and there were 4 serious TEAEs related to satri-cel. Participants were treated with 250-300x106, 375-400x106, or 600x206 cells, and objective response rate was 42.9% (n = 3) in GC/GEJ, 16.7% (n = 2) in PC, and 42.9% overall in DL3, which was selected as the recommended phase 2 dose.

REGENXBIO’s Wet AMD Gene Therapy Continues to Show Stable BCVA, Reduced Treatment Burden

January 18, 2024 - ABBV-RGX-314 gene therapy had a positive safety profile and reduced treatment burden in patients with wet age-related muscular dystrophy (AMD) treated in the phase 2 AAVIATE trial (NCT04514653).

“It should give us pause, that we could have the ability to reduce the treatment burden to our patients safely, which is phenomenal because we have had other drugs that have been administered by various other routes that have, unfortunately, caused severe inflammation. This seems to be well-tolerated in the suprachoroidal space," AAVIATE investigator David Boyer, MD, senior partner, Retina Vitreous Associates Medical Group, told CGTLive.

Investigators found that patients treated with ABBV-RGX-314 continued to demonstrate stable BCVA and CRT at 6 months, and anti-VEGF treatment burden was significantly reduced after administration of the therapy. The highest reduction was seen in dose level 3, in which patients had an 80% reduction in annualized injection rate and 50%remained injection-free.

AskBio’s Parkinson Disease Gene Therapy AB-1005 Demonstrates Safety in 18-Month Follow-up Data from Phase 1b Trial

January 11, 2024 - Asklepios BioPharmaceutical (AskBio)’s AB-1005 (AAV2-GDNF), an investigational adeno-associated viral vector serotype 2 (AAV2) gene therapy, has met its primary end point in 18-month follow-up data from a phase 1b clinical trial (NCT04167540) in patients with Parkinson disease (PD).

“We are encouraged by these early data, which show AB-1005 to be well-tolerated in this study in patients with mild to moderate PD,” Krystof Bankiewicz, MD, PhD, professor and vice chair of research, department of neurological surgery, Ohio State University, and professor emeritus and vice chair of research, University of California – San Francisco, and the cofounder of AskBio subsidiary Brain Neuropathy Bio, said in a statement. “Although there is still much to learn about this early-stage investigational gene therapy, these first findings will inform our work in this space and have the potential to contribute to the clinical advancement of AB-1005 for the treatment of PD.”

Among 11 patients with PD who were treated in the study, there were no serious treatment-related AEs at 18 months posttreatment. The 1-time bilateral, neurosurgical delivery of AB-1005 directly to the putamenwas well-tolerated and achieved 63% (±2%) of the putamen.

Neurona's Interneuron Cell Therapy Looks Promising in Drug-Resistant Mesial Temporal Lobe Epilepsy

January 15, 2024 - NRTX-1001 interneuron cell therapy was well-tolerated and showed favorable effects on seizure control in 5 participants with drug-resistant mesial temporal lobe epilepsy treated in a first-in-human phase 1/2 clinical trial (NCT05135091).

“Neurona’s regenerative cell therapy approach has the potential to provide a single-administration, non-destructive alternative for the treatment of drug-resistant MTLE,” David Blum, MD, chief medical officer, Neurona, said in a statement. “Currently, people with MTLE who are not responsive to anti-seizure medications have limited options, such as an invasive surgery that removes or destroys the affected brain tissue. FDA approval of novel tissue- and memory-sparing approaches could be transformative for such patients.”

The first 2 participants treated have continued to report over a 95% reduction in average monthly seizures 1 year after treatment and 2 of the 3 newer participants have demonstrated average total seizure reductions from baseline (64% and 75%). The other participant, with 1 month of follow-up, has continued to experience variable seizure counts consistent to their disease history, but longer follow-up may elucidate the results.

Passage Bio’s Gene Therapy PBFT02 Positively Impacts Biomarker Levels in Patients With Frontotemporal Dementia

January 15, 2024 - Passage Bio’s PBFT02, an investigational AAV vector-based gene therapy that is intended to deliver a functional copy of the granulin (GRN) gene, has demonstrated the ability to raise levels of cerebrospinal fluid (CSF) progranulin (PGRN) in patients with frontotemporal dementia (FTD) with GRN mutations treated in the phase 1/2 upliFT-D clinical trial (NCT04747431).

"We are proud to announce initial clinical data from our upliFT-D clinical trial, which showcases the ability of PBFT02 to elevate CSF progranulin to supraphysiologic levels at the lowest tested dose, Dose 1, up to 6 months post-treatment,” Mark Forman, MD, PhD, the chief medical officer at Passage Bio, said in a statement. “We believe these data, surpassing our expectations based on preclinical nonhuman primate models, validate the compelling potential of PBFT02 to address progranulin deficiency—a key driver of disease progression in individuals with FTD-GRN.”

at 30 days posttreatment, CSF PGRN had reached 10.7 to 17.3 ng/mL in the first 3 patients, which was greater than the levels seen in a population of 61 healthy adults used as a control, whose CSF PRGN was measured at 3.3 to 8.2 ng/mL. At 6 months posttreatment, supraphysiologic levels of CSF PGRN were maintained, with one patient showing 27.3 ng/mL. Levels of PRGN in the plasma in the 3 treated patients remained lower than those of the healthy control group up through the data cutoff.