CervoMed Announces New Data from Phase 2b Trial Demonstrating Neflamapimod's Potential as a Treatment for Dementia with Lewy Bodies
CervoMed (NASDAQ: CRVO) reported Phase 2b RewinD-LB results on Oct 8, 2025 showing neflamapimod activity in dementia with Lewy bodies (DLB).
In participants with plasma ptau181 <21 pg/mL (low likelihood of Alzheimer’s co-pathology), NFMD/B produced significant within-subject improvement on CDR-SB versus placebo (difference = −1.12, p=0.005) and improved clinical scales during the first 16 weeks of the Extension Phase. NFMD/B reduced risk of clinically meaningful progression by 67% versus NFMD/A over 32 weeks and 75% versus placebo over 16 weeks (both p<0.001).
Plasma GFAP fell with NFMD/B (median −16.7 pg/mL vs +5.8 pg/mL on placebo; median difference −23.1 pg/mL, p=0.016), and GFAP change correlated with CDR-SB change (p=0.036). The company expects FDA feedback on Phase 3 design in Q4 2025.
CervoMed (NASDAQ: CRVO) ha riportato i risultati di fase 2b RewinD-LB il 8 ottobre 2025, mostrando l’attività di neflamapimod nella demenza con corpi di Lewy (DLB).
Nei partecipanti con plasma ptau181 <21 pg/mL (bassa probabilità di co-patologia dell’Alzheimer), NFMD/B ha prodotto un significativo miglioramento entro lo stesso soggetto su CDR-SB rispetto al placebo (differenza = −1.12, p=0.005) e ha migliorato le scale cliniche durante i primi 16 settimane della Fase di Estensione. NFMD/B ha ridotto il rischio di progressione clinicamente significativa del 67% rispetto NFMD/A su 32 settimane e del 75% rispetto al placebo in 16 settimane (entrambi p<0.001).
La GFAP plasmatica è diminuita con NFMD/B (mediana −16,7 pg/mL contro +5,8 pg/mL con placebo; differenza mediana −23,1 pg/mL, p=0,016), e la variazione di GFAP si è correlata con la variazione di CDR-SB (p=0,036). L’azienda si aspetta un feedback della FDA sul design della Fase 3 nel Q4 2025.
CervoMed (NASDAQ: CRVO) informó resultados de la fase 2b RewinD-LB el 8 de octubre de 2025, mostrando actividad de la neflamapimod en la demencia con cuerpos de Lewy (DLB).
En participantes con plasma ptau181 <21 pg/mL (baja probabilidad de co-patología de Alzheimer), NFMD/B mostró una mejora significativa dentro del sujeto en CDR-SB frente a placebo (diferencia = −1.12, p=0.005) y mejoró las escalas clínicas durante las primeras 16 semanas de la Fase de Extensión. NFMD/B redujo el riesgo de progresión clínicamente significativa en un 67% frente a NFMD/A durante 32 semanas y 75% frente a placebo durante 16 semanas (ambos p<0.001).
La GFAP plasmática cayó con NFMD/B (mediana −16.7 pg/mL frente a +5.8 pg/mL con placebo; diferencia mediana −23.1 pg/mL, p=0.016), y el cambio de GFAP se correlacionó con el cambio de CDR-SB (p=0.036). La compañía espera comentarios de la FDA sobre el diseño de la Fase 3 en el Q4 de 2025.
CervoMed (NASDAQ: CRVO)는 2025년 10월 8일에 2b상 RewinD-LB 결과를 발표했으며 루이 바디 치매(DLB)에서 네플라마피모드의 활성을 보였습니다.
혈장 ptau181 <21 pg/mL(알츠하이머병 공병증의 낮은 가능성)인 참가자에서 NFMD/B는 CDR-SB에서 위약 대비 피험자 내 개선이 유의미했고(차이 = −1.12, p=0.005) 확장 단계의 처음 16주 동안 임상 척도도 개선되었습니다. NFMD/B는 32주 동안 NFMD/A 대비 임상적으로 의미 있는 진행 위험을 67% 감소시켰고 16주 동안 위약 대비 75% 감소시켰습니다(두 경우 p<0.001).
GFAP 혈장 수치는 NFMD/B에서 감소했고(중위값 −16.7 pg/mL 대 위약의 +5.8 pg/mL; 중위 차이 −23.1 pg/mL, p=0.016), GFAP 변화는 CDR-SB 변화와 상관관계가 있었습니다(p=0.036). 회사는 2025년 4분기 FDA의 3상 설계에 대한 피드백을 기대합니다.
CervoMed (NASDAQ: CRVO) a annoncé les résultats de la phase 2b RewinD-LB le 8 octobre 2025, montrant l’activité du néflamapimod dans la démence à corps de Lewy (DLB).
Chez les participants dont le plasma ptau181 <21 pg/mL (faible probabilité de co-pathologie avec Alzheimer), NFMD/B a produit une amélioration significative intra-sujet sur le CDR-SB par rapport au placebo (différence = −1,12, p=0,005) et a amélioré les échelles cliniques au cours des 16 premières semaines de la phase d’extension. NFMD/B a réduit le risque de progression cliniquement significative de 67% par rapport à NFMD/A sur 32 semaines et de 75% par rapport au placebo sur 16 semaines (les deux p<0,001).
Le plasma GFAP a diminué avec NFMD/B (médiane −16,7 pg/mL contre +5,8 pg/mL pour le placebo; différence médiane −23,1 pg/mL, p=0,016), et le changement de GFAP était corrélé au changement de CDR-SB (p=0,036). L’entreprise attend des retours de la FDA sur le design de la phase 3 au cours du Q4 2025.
CervoMed (NASDAQ: CRVO) meldete am 8. Oktober 2025 Ergebnisse der Phase-2b-RewinD-LB und zeigte die Aktivität von Neflamapimod bei Demenz mit Lewy-Körpern (DLB).
Bei Teilnehmern mit Plasma ptau181 <21 pg/mL (geringe Wahrscheinlichkeit einer Alzheimer-Kofaktoren-Pathologie) zeigte NFMD/B eine signifikante intraindividuelle Verbesserung am CDR-SB im Vergleich zu Placebo (Differenz = −1,12, p=0,005) und verbesserte klinische Skalen in den ersten 16 Wochen der Erweiterungsphase. NFMD/B senkte das Risiko eines klinisch bedeutsamen Fortschreitens um 67% gegenüber NFMD/A über 32 Wochen und um 75% gegenüber Placebo über 16 Wochen (beide p<0,001).
Plasma-GFAP sank unter NFMD/B (Median −16,7 pg/mL vs +5,8 pg/mL bei Placebo; Medianunterschied −23,1 pg/mL, p=0,016), und GFAP-Veränderung korrelierte mit CDR-SB-Veränderung (p=0,036). Das Unternehmen erwartet Rückmeldungen der FDA zum Design der Phase-3-Studie im 4. Quartal 2025.
CervoMed (NASDAQ: CRVO) أبلغت عن نتائج المرحلة 2b RewinD-LB في 8 أكتوبر 2025، موضحة نشاط نيفلامابي mod في الخرف الناتج عن أجسام ليوي (DLB).
بين المشاركين الذين كانت بلازما ptau181 <21 pg/mL (احتمالية منخفضة لتواجد مرض ألزهايمر المصاحب)، أظهر NFMD/B تحسنًا ذاتيًا هامًا داخل الشخص على CDR-SB مقابل الدواء الوهمي (الفرق = −1.12، ص=0.005) وتحسن في المقاييس السريرية خلال أول 16 أسبوعًا من مرحلة التوسيع. راجع NFMD/B انخفاض مخاطر التقدم الإكلينيكي بشكل معنوي بنسبة 67% مقابل NFMD/A خلال 32 أسبوعًا وبنسبة 75% مقابل الدواء الوهمي خلال 16 أسبوعًا (كلاهما ص<0.001).
انخفض GFAP البلازمي مع NFMD/B (الوسيط −16.7 pg/mL مقابل +5.8 pg/mL مع الدواء الوهمي؛ الفارق الوسيط −23.1 pg/mL، ص=0.016)، وتوافق تغير GFAP مع تغير CDR-SB (ص=0.036). تتوقع الشركة تعليقات FDA على تصميم المرحلة 3 في الربع الرابع من 2025.
CervoMed (NASDAQ: CRVO) 于 2025 年 10 月 8 日公布了 2b 期 RewinD-LB 的结果，显示 neflamapimod 在路易体痴呆（DLB）中的活性。
在血浆 ptau181 <21 pg/mL（阿尔茨海默共病的可能性较低）的参与者中，NFMD/B 在 CDR-SB 相对于安慰剂显示出显著的个体内改进（差异 = −1.12，p=0.005），并在扩展阶段的前 16 周内改善了临床量表。NFMD/B 将相对于 NFMD/A 的临床进展风险在 32 周内降低了 67%，相对于安慰剂在 16 周内降低了 75%（两者 p<0.001）。
血浆 GFAP 在 NFMD/B 组下降（中位数 −16.7 pg/mL，与安慰剂的 +5.8 pg/mL 相比；中位差 −23.1 pg/mL，p=0.016），GFAP 的变化与 CDR-SB 的变化相关（p=0.036）。公司预计 2025 年第 4 季对 Phase 3 设计获得 FDA 的反馈。
- Within-subject CDR-SB improvement of −1.12 (p=0.005)
- NFMD/B cut progression risk by 67% versus NFMD/A over 32 weeks
- NFMD/B cut progression risk by 75% versus placebo over 16 weeks
- Plasma GFAP median reduction −23.1 pg/mL versus placebo (p=0.016)
- GFAP change correlated with CDR-SB change (p=0.036)
- Initial Phase 16-week primary endpoint trend for NFMD/A versus placebo (difference −0.53, p=0.10)
- Efficacy depended on drug formulation: NFMD/A underperformed NFMD/B
- Subset efficacy reported in participants with ptau181 <21 pg/mL only
Insights
Phase 2b subgroup shows clinically and biomarker‑linked benefit for neflamapimod in DLB patients without AD co‑pathology; Phase 3 design and FDA feedback due
CervoMed reported that, in participants with plasma ptau181 <21 pg/mL (low likelihood of AD co‑pathology), the drug batch achieving target exposure (NFMD/B) produced significant within‑subject improvement on the primary clinical measure (CDR‑SB) versus placebo and versus the lower‑exposure batch. The company also reported a correlated reduction in plasma GFAP, with a paired within‑subject median change of −23.1 pg/mL (p=0.016) representing an estimated
The reported effects align a clinical endpoint with a biologic marker, strengthening the internal consistency of the result. Key dependencies remain: the findings are subgroup and within‑subject comparisons rather than a standalone between‑group primary endpoint in the full randomized cohort, and efficacy appears tied to the higher‑exposure NFMD/B formulation. The analysis plan was amended post‑design to use a lower ptau181 cutoff (<21 pg/mL), which narrows the target population to those without AD co‑pathology.
Items to watch: formal FDA feedback on Phase 3 design expected in
Significant improvement relative to placebo on primary outcome measure, change in Clinical Dementia Rating Sum of Boxes (CDR-SB), demonstrated in a within-subject analysis in participants with low likelihood of having Alzheimer’s disease (AD) co-pathology
Significant reduction in plasma levels of a well-established biomarker of neurodegeneration, plasma glial fibrillary acidic protein (GFAP), correlated to treatment response assessed by CDR-SB
CervoMed anticipates U.S. Food and Drug Administration (FDA) feedback on Phase 3 trial design in the fourth quarter of 2025
BOSTON, Oct. 08, 2025 (GLOBE NEWSWIRE) -- CervoMed Inc. (NASDAQ: CRVO), a clinical stage company focused on developing treatments for age-related neurologic disorders (CervoMed or the Company), today announced additional data from its Phase 2b RewinD-LB trial, further demonstrating neflamapimod’s potential as a treatment for dementia with Lewy bodies (DLB).
“With October recognized as Lewy Body Dementia Awareness Month, we are especially proud to share these new data from our Phase 2b RewinD-LB trial,” said John Alam, M.D., Chief Executive Officer of CervoMed and Co-Principal Investigator of the RewinD-LB trial. “The significant improvements compared to placebo in change in CDR-SB observed in the within-subject comparison, along with correlated reductions in a key biomarker of neurodegeneration further strengthen our confidence in neflamapimod’s potential as a treatment for DLB. Together with other insights gained from Phase 2b, these results have enabled us to refine and optimize the design of our planned Phase 3 trial as we await FDA feedback later this quarter.”
New Results from the Phase 2b RewinD-LB Trial1
The results announced today (presentation here) are based on the final analyses of the RewinD-LB trial, conducted after the August 2025 database lock for the full 48-week trial (16 weeks placebo-controlled (Initial Phase), followed by a 32-week neflamapimod-only extension (Extension Phase)). In addition to confirming previously reported findings, today’s announcement also includes:
- A subgroup analysis of participants with a low likelihood of AD co-pathology, defined by the criteria the Company expects to use in its planned Phase 3 trial in patients with DLB; and
- Further analyses of the RewinD-LB trial’s primary biomarker endpoint, plasma GFAP.
Results in Participants Whose Plasma ptau181 Levels Were Below 21 pg/mL at Screening, Indicating a Low Likelihood of AD Co-Pathology
To enrich enrollment for participants without AD co-pathology, only individuals with plasma ptau181 <27.2 pg/mL2 were randomized in the RewinD-LB trial. Based on the limited data available at the time the trial was designed, this 27.2 pg/mL threshold was estimated to be an appropriate cut-off for distinguishing patients with AD co-pathology from those without.
Recently, however, the first large, international multicenter study (n=1298) of the diagnostic performance of plasma ptau181 along the continuum of AD and non-AD dementias3 identified a lower threshold – 21 pg/mL – as the high-sensitivity cutoff for detecting AD pathology. Based on this progress in understanding of using ptau181 to detect AD pathology and the Company’s belief that neflamapimod is most effective as a treatment for the roughly
In the subset of participants whose plasma ptau181 levels were below 21 pg/mL at screening, results include:
- Initial Phase: On the primary endpoint of change in CDR-SB over 16 weeks, there was a trend toward NFMD/A (Drug product batch that did not achieve targeted plasma drug concentrations, “old capsules”)4 relative to placebo (difference −0.53, p=0.10, linear mixed-effects model) during the Initial Phase of the trial.
- Extension Phase (First 16 Weeks): NFMD/B (drug product batch that achieved plasma drug concentrations, “new capsules”)4 demonstrated significant improvement versus NFMD/A on CDR-SB (−0.58, p=0.024), as well on the ADCS-CGIC, Dementia-Cognitive Fluctuations Scale, and International Shopping List Test-Recognition, over the first 16 weeks of the Extension Phase.
- Within-Subject Comparison to Placebo: Participants who transitioned from placebo in the Initial Phase to NFMD/B in the Extension Phase showed significant improvement on change in CDR-SB (difference= -1.12, p=0.005) and on ADCS-CGIC (difference=–0.82, p=0.004) while they were on NFMD/B relative to when on placebo over the respective 16-week periods.
- Time-to-Progression Analysis: NFMD/B reduced the risk of clinically meaningful progression (≥1.5-point CDR-SB increase) by
67% versus NFMD/A over 32 weeks (p<0.001) and by75% versus placebo over 16 weeks (p<0.001).
New Analyses of Neflamapimod’s Effect on Plasma GFAP, a Well-Established Biomarker of Neurodegenerative Disease Progression
In August 2025, CervoMed reported that, during the Extension Phase, neflamapimod significantly reduced plasma GFAP levels, the primary biomarker endpoint, in participants who had received 12 or more weeks of NMFD/B. This effect was not observed in participants who only received NMFD/A.
The new plasma GFAP analyses in the subset of participants whose plasma ptau181 levels were below 21 pg/mL at screening are summarized below:
- Within-Subject Comparison to Placebo: Among participants who received placebo during the Initial Phase and then transitioned to NMFD/B in the Extension Phase, the change in plasma GFAP over 32 weeks of NMFD/B treatment was significantly lower than the change observed over 16 weeks of placebo treatment in the same individuals (−16.7 pg/mL with NMFD/B vs. +5.8 pg/mL with placebo; median difference −23.1 pg/mL, p=0.016, paired Wilcoxon test). This represents an estimated
50% reduction in disease-specific elevation in plasma GFAP levels5. - Correlation with Clinical Outcomes: During the Extension Phase, in participants with a low likelihood of AD co-pathology, plasma GFAP change significantly correlated with CDR-SB change (p=0.036). Specifically, reductions in plasma GFAP were associated with improvements in CDR-SB scores (lower dementia severity), whereas increases in plasma GFAP corresponded to worsening scores. These findings directly correlate the biomarker effect to a clinically meaningful treatment response.
About the RewinD-LB Phase 2b Trial in Dementia with Lewy Bodies
The initial phase of RewinD-LB was a randomized, 16-week, double-blind, placebo-controlled clinical trial evaluating oral neflamapimod (40mg TID) in 159 participants with DLB, followed by a 32-week neflamapimod-only treatment Extension phase. Patients with AD co-pathology, as assessed by plasma ptau181 levels, were excluded from the trial. Compared to patients with “pure” DLB – who may comprise up to
About CervoMed
CervoMed is a clinical-stage company focused on developing treatments for age-related neurologic disorders. The Company is currently developing neflamapimod, an investigational, orally administered small molecule brain penetrant that inhibits p38 mitogen-activated protein kinase alpha. Neflamapimod has the potential to treat synaptic dysfunction, the reversible aspect of the underlying neurodegenerative processes that cause disease in DLB and certain other major neurological disorders. The Company’s recently completed Phase 2b trial evaluated neflamapimod in patients with DLB.
Forward-Looking Statements
This press release includes express and implied forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, regarding the intentions, plans, beliefs, expectations or forecasts for the future of the Company, including, but not limited to: the therapeutic potential of neflamapimod, including the degree of sustainability of any therapeutic effects; the anticipated timing and achievement of clinical and development milestones, including the Company’s announcement of additional data, if any, from the RewinD-LB Phase 2b clinical trial and any meeting or correspondence between the Company and the FDA; any other expected or implied benefits or results, including that any initial clinical results observed with respect to neflamapimod in the RewinD-LB trial will be replicated in later trials; and the timing of the initiation of any potential future trials or interactions with regulatory authorities, including the Company’s need to acquire sufficient funding for any Phase 3 trial of neflamapimod in DLB. Terms such as “believes,” “estimates,” “anticipates,” “expects,” “plans,” “aims,” “seeks,” “intends,” “may,” “might,” “could,” “might,” “will,” “should,” “approximately,” “potential,” “target,” “project,” “contemplate,” “predict,” “forecast,” “continue,” or other words that convey uncertainty of future events or outcomes (including the negative of these terms) may identify these forward-looking statements. Although there is believed to be reasonable basis for each forward-looking statement contained herein, forward-looking statements by their nature involve risks and uncertainties, known and unknown, many of which are beyond the Company’s control and, as a result, actual results could differ materially from those expressed or implied in any forward-looking statement. Particular risks and uncertainties include, among other things, those related to: the Company’s available cash resources and the availability of additional funds on acceptable terms; the results of the Company’s clinical trials, including RewinD-LB; the likelihood and timing of any regulatory approval of neflamapimod or the nature of any feedback the Company may receive from the FDA; the ability to implement business plans, forecasts, and other expectations in the future; general economic, political, business, industry, and market conditions, inflationary pressures, and geopolitical conflicts; and the other factors discussed under the heading “Risk Factors” in the Company’s Annual Report on Form 10-K for the year ended December 31, 2024 filed with the U.S. Securities and Exchange Commission (SEC) on March 17, 2025, and other filings that the Company may file from time to time with the SEC. Any forward-looking statements in this press release speak only as of the date hereof (or such earlier date as may be identified). The Company does not undertake any obligation to update such forward-looking statements to reflect events or circumstances after the date of this press release, except to the extent required by law.
Contacts
Investors:
PJ Kelleher
LifeSci Advisors
Investors@cervomed.com
617-430-7579
Media:
Argot Partners
liza@argotpartners.com
212-600-1902
1 All analyses reported are exploratory in nature.
2 The Company has historically reported plasma ptau181 levels based on the scale associated with the Quanterix Simoa ptau181 Advantage v2.0 assay kit. In this press release and going forward, the Company will report plasma ptau181 levels based on the scale associated with the current Quanterix Simoa ptau181 Advantage v2.1 assay kit, which was utilized in the RewinD-LB trial. Quantitative values on the v2.1 scale are approximately ten-fold higher than the corresponding values on the v2.0 scale.
3 Alzheimer’s & Dement. 2025 Jun 23;21(6):e14573. doi: 10.1002/alz.14573
4 In the RewinD-LB trial, two different batches of drug product were administered. One batch of capsules, utilized in placebo-controlled phase and initially during the extension – which we refer to as NFMD/A or the “Old Capsules” – did not achieve expected and targeted average plasma drug concentrations. The other batch of capsules, introduced during the extension – which we refer to as NFMD/B or the “New Capsules” – achieved the targeted average plasma drug concentrations.
5 Based on mean ~150 pg/mL in participants with DLB vs. ~100 pg/mL in healthy controls; Doecke et al., 2025.
FAQ
What Phase 2b results did CervoMed (CRVO) announce on October 8, 2025?
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