JAMA Neurology Publishes Results from PARADIGM Phase 2b Trial of PrimeC in ALS Demonstrating Meaningful Clinical Outcomes and Biological Activity
Rhea-AI Summary
NeuroSense (NASDAQ: NRSN) announced JAMA Neurology publication of PARADIGM Phase 2b results for PrimeC in ALS, reporting slower functional decline, reduced complications, and biomarker activity.
Key findings: 7.92-point ALSFRS-R advantage at 18 months (~36% slowing, p=0.007), 64% relative reduction in ALS complications (p=0.02), favorable safety vs placebo, and modulation of iron and microRNA biomarkers.
Positive
- ALSFRS-R +7.92 points at 18 months (~36% slower progression, p=0.007)
- 64% relative risk reduction in ALS-related complications (respiratory failure, hospitalization, or death; p=0.02)
- Safety comparable to placebo over 18 months with mostly mild-to-moderate transient adverse events
- Biomarker engagement: preservation of transferrin, stabilization of ferritin, and downregulation of four ALS-associated microRNAs
Negative
- Small trial size: 68 participants enrolled, limiting statistical power
- Trial design limitation: study was not powered to demonstrate definitive efficacy for regulatory approval
News Market Reaction – NRSN
In the Mar 16 session, NRSN declined 5.61%, reflecting a notable negative market reaction. Argus tracked a peak move of +12.5% during that session. Argus tracked a trough of -17.4% from its starting point during tracking. Our momentum scanner triggered 14 alerts that day, indicating notable trading interest and price volatility. Trading volume was exceptionally heavy at 6.3x the daily average, suggesting significant selling pressure.
Data tracked by StockTitan Argus on the day of publication.
Key Figures
Historical Context
| Date | Event | Sentiment | 24h Move | Catalyst |
|---|---|---|---|---|
| Mar 09 | ALS survival data | Positive | -3.0% | Presentation of long-term survival data from PARADIGM showing 65% death risk reduction. |
| Feb 18 | ALS survival update | Positive | -14.7% | Extended PARADIGM data with >14-month median survival benefit and significant mortality reduction. |
| Feb 09 | PrimeC IP expansion | Positive | +8.5% | Australian patent grant extending PrimeC composition protection through October 2042. |
| Jan 21 | Alzheimer’s patent | Positive | -5.2% | U.S. patent covering PrimeC for Alzheimer’s disease with protection through 2043. |
| Jan 08 | SAB appointment | Positive | +12.4% | Addition of renowned Alzheimer’s expert to SAB and reiteration of favorable RoAD safety data. |
24h Move is the share-price change in the day after each event; other market factors may also have contributed.
Recent history shows several positive clinical and IP updates followed by mixed to negative 24-hour price reactions, indicating a tendency toward sell-the-news behavior on good developments.
Over recent months, NeuroSense reported multiple advances: extended PARADIGM survival data with a 65% reduction in risk of death and >14-month median survival benefit, patent grants extending protection for PrimeC into 2042–2043, and the addition of a leading Alzheimer’s expert to its SAB. Despite generally positive milestones, including favorable safety and biomarker signals, 24-hour price reactions were often negative or mixed. Today’s JAMA Neurology publication reinforces the same PARADIGM dataset with detailed functional and biomarker outcomes.
Key Terms
phase 2b medical
randomized, double-blind, placebo-controlled medical
open-label extension medical
alsfrs-r medical
bulbar function medical
biomarkers medical
microRNAs medical
relative risk reduction medical
AI-generated analysis. How Rhea-AI works. Not financial advice.
The Journal of the American Medical Association (JAMA Neurology) publication highlights consistent clinical and biomarker findings from NeuroSense PARADIGM Phase 2b trial in ALS, including slower functional decline, reduced risk of ALS-related complications, and modulation of disease-relevant biomarkers
Earlier today, Mass General Brigham (MGB) and Barrow Neurological Institute (BNI) issued a joint announcement highlighting the publication and the contributions of the investigators involved in the PARADIGM trial. NeuroSense is honored to collaborate with these leading ALS research centers of excellence and their distinguished clinical teams in advancing research for people living with ALS.
PARADIGM was a randomized, double-blind, placebo-controlled trial that evaluated the safety, biological activity, and potential clinical effects of PrimeC during a 6-month blinded treatment period followed by a 12-month open-label extension.
PrimeC is a novel fixed-dose oral combination formulated in a synchronized extended-release composition designed to concurrently address three key mechanisms implicated in ALS progression: neuroinflammation, iron dysregulation, and microRNA-mediated regulatory pathways.
The publication was authored by a distinguished international group of ALS investigators, including Merit Cudkowicz, MD, MSc (Mass General Brigham and Harvard Medical School), Vivian Drory, MD (Tel-Aviv Sourasky Medical Centre), Adriano Chiò, MD, PhD (University of
Key highlights from the PARADIGM phase 2b study published
- Strong safety and tolerability profile: PrimeC demonstrated a safety profile comparable to placebo over 18 months, with most treatment-related adverse events mild to moderate and transient.
- Clinically meaningful functional outcomes: Continuous treatment with PrimeC was associated with slower functional decline and improved long-term outcomes, including a 7.92-point advantage in ALSFRS-R at 18 months, which represents over
36% benefit of slowing disease progression (p=0.007) and significant improvement in bulbar function (P=0.001). - Reduction in risk of major ALS complications: Early initiation of PrimeC was associated with a
64% relative reduction in risk of ALS-related complications (p=0.02), including respiratory failure, hospitalization, or death. - Biological evidence supporting disease modification: PrimeC treatment was associated with significant modulation of ALS-related microRNAs and iron-regulatory biomarkers, supporting its biological activity and reinforcing the potential for disease-modifying effects.
- Supports advancement to Phase 3: These findings support the continued clinical development of PrimeC and its advancement to a confirmatory Phase 3 clinical trial in ALS.
"ALS is one of the most serious neurological diseases, and there is an urgent need for therapies that can meaningfully alter its course," said Merit Cudkowicz, MD, MSc, Director of the Healey & AMG Center for ALS at Mass General Brigham and Julieanne Dorn Professor of Neurology at Harvard Medical School. "What is particularly noteworthy about the PARADIGM results is the consistency of the findings across clinical outcomes and disease-relevant biomarkers, in addition to good safety. These results provide a strong scientific rationale for continuing the clinical development of PrimeC and support its evaluation in a larger confirmatory Phase 3 trial."
"What stands out about the PARADIGM study is the multiple clinical endpoints suggest the same level of clinical benefit and that multiple biomarkers are consistent with clinical endpoints," said Jeremy M. Shefner, MD, PhD, Professor of Neurology at the Barrow Neurological Institute and corresponding author of the publication. "Together, these findings provide a strong scientific foundation for advancing PrimeC into a Phase 3 trial designed to validate its impact for patients."
"The publication of the PARADIGM results in the prestigious JAMA Neurology represents an important milestone for NeuroSense and for people living with ALS," said Ferenc Tracik, MD, Chief Medical Officer of NeuroSense Therapeutics. "This article integrates PrimeC's safety, clinical, and biomarker data over 18 months. The consistent findings of slower functional decline, reduced risk of ALS-related complications, and modulation of iron-regulatory and microRNA biomarkers strengthen confidence in PrimeC's potential as a disease-modifying therapy. These findings directly informed the design of our Phase 3 trial, which has received FDA clearance to proceed."
PARADIGM Study Overview
PARADIGM was a multinational Phase 2b randomized, double-blind, placebo-controlled clinical trial conducted at leading ALS referral centers in
The study enrolled 68 participants with definite or probable ALS, randomized in a 2:1 ratio to receive PrimeC or placebo for six months. The double-blind phase was followed by a 12-month open-label extension, during which all participants received PrimeC while maintaining blinding to original treatment assignment.
Even though the trial was not powered to demonstrate definitive efficacy, participants who received PrimeC from the outset maintained a clinically meaningful 7.92-point functional advantage in ALSFRS-R at 18 months, which represents over
In addition, ALS complication-free survival demonstrated a
Biomarker Findings
The trial also demonstrated biological activity consistent with PrimeC's proposed multi-pathway mechanism.
Markers of iron metabolism, which are frequently dysregulated in ALS, showed favorable significant changes, including preservation of transferrin levels and stabilization of ferritin.
In parallel, plasma microRNA analysis revealed statistically significant downregulation of ALS-associated microRNAs miR-199a-3p, miR-199a-5p, miR-181a-5p, and miR-181b-5p, which have been linked to disease severity and prognosis.
Together, these findings provide biological evidence that PrimeC engages disease-relevant pathways and support its continued development as a potential disease-modifying therapy.
About PrimeC
PrimeC is an investigational fixed-dose oral combination therapy composed of celecoxib and ciprofloxacin in a synchronized extended-release formulation. The therapy is designed to simultaneously target multiple biological mechanisms implicated in ALS progression, including neuroinflammation, iron dysregulation, and microRNA dysregulation.
The therapeutic rationale for PrimeC is supported by preclinical evidence across ALS disease models and human induced pluripotent stem cell–derived motor neuron systems and has now been evaluated in a randomized Phase 2b clinical trial.
About NeuroSense Therapeutics
NeuroSense Therapeutics is a clinical-stage biopharmaceutical company focused on developing disease-modifying therapies for people living with ALS and other neurodegenerative diseases. The company's lead program, PrimeC, is designed to simultaneously target multiple biological pathways implicated in ALS progression.
Forward-Looking Statements
This press release contains "forward-looking statements" that are subject to substantial risks and uncertainties. All statements, other than statements of historical fact, contained in this press release are forward-looking statements. Forward-looking statements contained in this press release may be identified by the use of words such as "anticipate," "believe," "contemplate," "could," "estimate," "expect," "intend," "seek," "may," "might," "plan," "potential," "predict," "project," "target," "aim," "should," "will" "would," or the negative of these words or other similar expressions, although not all forward-looking statements contain these words. Forward-looking statements are based on NeuroSense Therapeutics' current expectations and are subject to inherent uncertainties, risks and assumptions that are difficult to predict and include statements regarding the timing of regulatory filings, meetings and regulatory decisions. Further, certain forward-looking statements, including statements regarding future development of PrimeC, are based on assumptions as to future events that may not prove to be accurate. The future events and trends may not occur and actual results could differ materially and adversely from those anticipated or implied in the forward looking statements. These risks include the uncertainty regarding outcomes and the timing of current and future clinical trials; the risk the PrimeC will not advance towards later-stage development, timing for reporting data, including from the study of PrimeC in Alzheimer's disease; that the study will not be successful; the ability of NeuroSense to remain listed on Nasdaq; and other risks and uncertainties set forth in NeuroSense's filings with the Securities and Exchange Commission (SEC). You should not rely on these statements as representing our views in the future. More information about the risks and uncertainties affecting NeuroSense is contained under the heading "Risk Factors" in the Annual Report on Form 20-F filed with the Securities and Exchange Commission on April 7, 2025 and NeuroSense's subsequent filings with the SEC. Forward-looking statements contained in this announcement are made as of this date, and NeuroSense undertakes no duty to update such information except as required under applicable law.
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