12-Month PARADIGM Data Showcases PrimeC’s Ability to Extend Survival in ALS

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in both the overall population and a per-procotol population, PrimeC-treated individuals experienced improvements on ALS Functional Rating Scale and increased survival compared with placebo.

Merit Cudkowicz, MD, MSc, chair of neurology and director of the Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital

Merit Cudkowicz, MD, MSc

Newly announced 12-month data from the phase 2b PARADIGM study (NCT05357950) showed that treatment with investigational PrimeC (NeuroSense) resulted in a statistically significant improvement in disease progression and survival in patients with amyotrophic lateral sclerosis (ALS). PrimeC, a novel extended-release oral formulation composed of ciprofloxacin and celecoxib, 2 FDA-approved drugs, is gearing up to be tested in a phase 3 study to further test its effects in this patient population.1

In the randomized, double-blind, placebo-controlled trial, treatment with PrimeC resulted in a statistically significant difference of 6.5 points on ALS Functional Rating Scale-Revised (ALSFRS) over a 12-month time period. This translated to a 36% improvement, and a highly significant P value of 0.009. Furthermore, those on the active therapy demonstrated greater extended survival than placebo, by 43%.

Within the study, 96% of 68-patient cohort who completed the 6-month double-blind portion of the trial chose to receive treatment with PrimeC through a 12-month open-label extension. When assessing the per-protocol population, 12-month data revealed an even greater treatment effect, with a difference of 7.7 points (P = .003) on ALSFRS between the groups, translating to a 40% improvement in patients who started PrimeC from the beginning of the study. In this subset, PrimeC-treated patients demonstrated a 63% enhanced survival than those who received placebo.

"These exciting long-term results demonstrate how study participants experienced more slowing of progression over time with PrimeC as measured against ALSFRS-R, which is the current gold-standard scale used in ALS drug development,” Merit Cudkowicz, MD, MSc, chair of neurology and director of the Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital, said in a statement.1 "The need for new treatments for people living with ALS has never been greater. PrimeC has great potential based on its mode of action and the phase 2 trial results and warrants further evaluation in a Phase 3 trial in an expeditious manner."

The 6-month analysis, announced in December 2023, showed a 29% difference in ALSFRS between PrimeC-treated patients and those on placebo. At the time, investigators also recorded a 13% treatment difference favoring the investigational agent on slow vital capacity, a measure of respiratory function. The trial originally had 1 misdiagnosed participant; however, all other participants who have completed the 18-month trial have opted to continue treatment of PrimeC by joining a subsequent investigator-initiated trial.2

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"The promising results from the 12-month PARADIGM study highlight the significant potential of PrimeC as a disease-modifying drug for ALS,” Vivian Drory, MD, head of the ALS Clinic at Tel-Aviv Sourasky Medical Center, said in a statement.1 "These findings underscore the importance of early intervention, which can lead to more substantial benefits, and provide valuable insights that will inform the design of the Company's Phase 3 study, increasing the likelihood of success."

More recently, in early May, NeuroSense announced 6-month data from PARADIGM highlighting PrimeC’s impact on a subgroup of patients with high-risk ALS. These patients, defined by the European Network for the Cure of ALS (ENCALS) Risk Factor as those with a higher risk for rapid disease progression, demonstrated a 43% difference compared with placebo on ALSFRS-R, the primary end point. Overall, this translated to a 5.04-point difference in favor of PrimeC (CI, 0.862-9.214; n = 38).

The study also evaluated the effect of PrimeC in a subgroup of newly diagnosed patients who had symptoms for up to 12 months prior to the baseline visit. In these participants, treatment with the agent resulted in a 52% slowing of disease progression (P = .008) vs placebo in the PP population analysis. This translated to a 7.76-point difference in the ALSFRS-R in favor of PrimeC (CI, 2.27-13.25; n = 22). In the ITT population, newly diagnosed participants treated with active therapy experienced a 36% reduction (P = .14) in disease progression, which translated to a 4.56-point difference in the ALSFRS-R in favor of PrimeC (CI, –1.6 to 10.72; n = 25).

Cudkowicz, an ALS expert, sat down with NeurologyLive® at the 2024 American Academy of Neurology Annual Meeting, to discuss the primary drugs used in PrimeC, and why they were chosen for ALS treatment. In the clip below, she provides clinical insight on the safety, efficacy, and biomarker findings from the trial, as well as expectations for the upcoming phase 3 study.

REFERENCES
1. NeuroSense demonstrates statistically significant efficacy and survival benefits in people living with ALS: the promising results from the 12-month PARADIGM study highlight PrimeC’s potential as a disease modifying drug. News release. July 1, 2024. Accessed July 1, 2024. https://www.prnewswire.com/news-releases/neurosense-demonstrates-statistically-significant-efficacy-and-survival-benefits-in-people-living-with-als-the-promising-results-from-the-12-month-paradigm-study-highlight-primecs-potential-as-a-disease-modifying-drug-302186838.html
2. NeuroSense’s phase 2b ALS trial achieves primary safety and tolerability & secondary clinical end points. News release. NeuroSense. December 5, 2023. Accessed July 1, 2024. https://neurosense.investorroom.com/2023-12-05-NeuroSenses-Phase-2b-ALS-Trial-Achieves-Primary-Safety-and-Tolerability-Secondary-Clinical-Efficacy-Endpoints
3. NeuroSense announces new positive data analysis from PARADIGM clinical trial demonstrating statistically significant slowing of disease progression in high-risk ALS patients. News release. NeuroSense. May 7, 2024. Accessed July 1, 2024. https://www.prnewswire.com/news-releases/neurosense-announces-new-positive-data-analysis-from-paradigm-clinical-trial-demonstrating-statistically-significant-slowing-of-disease-progression-in-high-risk-als-patients-302137999.html
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