Immunity Pharma Announces Positive Top Line Results from Phase 2a Trial with IPL344 in ALS Patients

2024-01-17

临床结果临床2期孤儿药临床1期

Treatment with IPL344 was well tolerated

Changes in the slope of decline in ALSFRS-R demonstrated 48% slower disease progression (p=0.028); and 64% slower progression when adjusted for disease stage and rate (p=0.034)

Study suggests benefits in weight gain, respiration, and survival

Plasma neurofilament (NfL) reduction observed following IPL344 treatment

JERUSALEM, Jan. 17, 2024 /PRNewswire/ -- Immunity Pharma, a clinical-stage neurology-focused biopharmaceutical company, today announced positive top line results from the Phase 2a trial with IPL344 in amyotrophic lateral sclerosis (ALS) patients. The study demonstrated statistically significant efficacy as measured by change in the slope decline of ALSFRS-R. The drug was well tolerated, and the study suggests benefits in weight gain, respiration, and survival. Neurofilament (NfL) reduction was observed following IPL344 treatment.

In this study, once-daily treatment with IPL344 for up to 36 months was well tolerated, with no major drug related serious adverse events (SAE). No participants discontinued treatment due to drug-related AEs. IPL344 treated patients showed a mean slope of decline in ALSFRS-R of -0.53, equating 48% slower disease progression (p=0.028). Adjustment for disease stage and rate-indicating covariates, indicated a 64% slower ALSFRS-R progression (p=0.034). In addition, a statistically significant increase rather than decrease was observed in body weight of IPL344 treated patients (p=0.02; compared to the PRO-ACT database of patients treated with placebo). Median survival of patients in this study was 29 months vs. 19 months of placebo treated patients in the ceftriaxone study (post-treatment follow-up is still ongoing), indicating a trend toward reduced risk of death in favor of IPL344 (p=0.13). There was a non-significant trend for preserved respiration capacity (44% slower reduction in average %SVC loss per month vs. historical placebo; p=0.15).

Biomarker data for plasma neurofilament light (NfL) levels were obtained for eight subjects. NfL concentrations were reduced during IPL344 treatment in all but one participant. In the six subjects that had blood sampling past the initial dose-escalating phase, plasma NfL concentrations were reduced by a mean of 20%, suggesting decrease of neuronal injury following IPL344 treatment.

"We are excited that treatment with IPL344 was well tolerated in people with ALS and demonstrated encouraging signs of efficacy across multiple parameters. This data will soon be submitted for publication in a scientific journal," said Dr. Ilana Cohen, Immunity Pharma's VP of R&D. "If confirmed in a subsequent larger phase 3 study, the magnitude of reduction in ALSFRS-R progression observed in this study is greater than that achieved with currently approved drugs."

"These early-stage data support further development of IPL344 as a treatment for ALS, and merit further investigation in a large number of participants. We intend to progress PL344 to a pivotal clinical trial in ALS," said Immunity's CEO, Eran Ovadia.

About the Phase 2a ALS Clinical Trial

The Phase 1/2a trial was an open-label study with once-daily IPL344 treatment administered IV (home administration). Subjects were allowed to stay in the study for up to 3 years. The study includes a 28-day Phase 1dose-escalating portion, after which subjects may continue to the Phase 2a portion of the study. The study was conducted at the Hadassah Medical Center in Jerusalem (NCT03652805, NCT03755167).

The Phase 1/2a study included nine participants with probable or definite ALS and a progression rate >0.55 points/month on the ALS functional rating scale-revised (ALSFRS-R) that received open-label treatment with once-daily IPL344 for up to 36 months. Efficacy outcomes included the rate of progression on ALSFRS-R, slow vital capacity (SVC), weight, and survival compared with historical placebo from the PRO-ACT database and ceftriaxone study. The statistical analysis included a method previously proposed by Dr. Schoenfeld designed to quantify inter-center and inter-study variability, to pinpoint whenever ALSFRS-R slowdown exceeds the normal variability. This analysis shows that, despite the small number of participants the magnitude of ALSFRS-R slope reduction is larger than the threshold needed for significance and is beyond that expected by inter-study variation.

About IPL344

IPL344 is a biologically active peptide that stimulates therapeutic cell-signaling processes including activation of the Akt pathway, which is down-regulated in neurodegenerative diseases. IPL344 was discovered in the Weizmann institute of Science, Israel, at Prof. Irun Cohen's Laboratory. IPL344 is being developed as an intravenous injection for the treatment of ALS initially through a Phase 1/2a clinical trial in ALS patients. IPL344 received orphan drug designation from FDA and EMA, which grants exclusivity for at least seven years.

About Immunity Pharma

Immunity Pharma Ltd. (IPL) is a privately-held clinical-stage neurology-focused biopharmaceutical company that develops therapies for neurodegenerative diseases, with an initial focus on Amyotrophic lateral sclerosis (ALS). IPL's drugs are biologically active peptides that stimulate therapeutic cell-signalling processes and mitigate progression of neurodegenerative diseases by inducing intra-cellular survival-supporting processes. IPL's drugs are being developed as treatment for ALS, Parkinson's disease and other neurodegenerative diseases.

For more information, please visit www.immunitypharma.com

SOURCE Immunity Pharma