Safety and efficacy of fenebrutinib in relapsing multiple sclerosis (FENopta): a multicentre, double-blind, randomised, placebo-controlled, phase 2 trial and open-label extension study

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F25%3A00082393" target="_blank" >RIV/00159816:_____/25:00082393 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14110/25:00141720

Výsledek na webu

<a href="https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(25)00174-7/" target="_blank" >https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(25)00174-7/</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/S1474-4422(25)00174-7" target="_blank" >10.1016/S1474-4422(25)00174-7</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Safety and efficacy of fenebrutinib in relapsing multiple sclerosis (FENopta): a multicentre, double-blind, randomised, placebo-controlled, phase 2 trial and open-label extension study

Popis výsledku v původním jazyce

Background The prospect for Bruton&apos;s tyrosine kinase (BTK) inhibition to meaningfully affect relapsing multiple sclerosis has recently been questioned due to inconsistent findings in the magnitude and sustainability of the effect of BTK inhibitors on disease activity. We assessed the safety, efficacy, and CSF drug concentrations of fenebrutinib, a highly selective, noncovalent, reversible BTK inhibitor, in patients with relapsing multiple sclerosis. Methods This multicentre, double-blind, randomised, placebo-controlled, phase 2 trial (FENopta) was conducted at 18 community centres and hospitals across six countries in Europe and North America. Patients with relapsing multiple sclerosis aged 18-55 years with an Expanded Disability Status Scale (EDSS) score of 0&lt;middle dot&gt;0-5&lt;middle dot&gt;5, and recent documented disease activity, were randomly assigned (2:1) to oral fenebrutinib (200 mg twice daily) or placebo for 12 weeks, using permuted blocks and stratified by the presence or absence of T1 gadolinium-enhancing (Gd+) lesions on the brain MRI at screening. The randomisation sequence was generated by an interactive voice or web response system and both patients and investigators were masked to treatment allocation. Participants could enter an optional open-label extension study to receive fenebrutinib for up to 192 weeks. The primary efficacy endpoint was the total number of new T1 Gd+ lesions on brain MRI at weeks 4, 8, and 12; with additional MRI assessments at 48-week intervals during the open-label extension. Efficacy analyses were done on randomised patients with evaluable post-baseline MRIs; safety analyses used the safety-evaluable population. This study is registered with ClinicalTrials.gov, NCT05119569, and EudraCT, 2021-003772-14; recruitment is closed and the trial is ongoing. Findings Between March 1, 2022 and March 29, 2023, 109 patients with relapsing multiple sclerosis were randomly assigned treatment: 73 received fenebrutinib and 36 received placebo. 106 patients had evaluable post-baseline brain MRI scans and were assessed for efficacy in the fenebrutinib group (n=70) and placebo group (n=36). The combined number of new T1 Gd+ lesions at weeks 4, 8, and 12 were 0&lt;middle dot&gt;077 (95% CI 0&lt;middle dot&gt;043-0&lt;middle dot&gt;135) in the fenebrutinib group and 0&lt;middle dot&gt;245 (0&lt;middle dot&gt;144-0&lt;middle dot&gt;418) in the placebo group (69% relative reduction [95% CI 34-85]; p=0&lt;middle dot&gt;0022). During the open-label extension, through week 48, the unadjusted annualised relapse rate was 0&lt;middle dot&gt;04 and 95 (96%) of 99 patients were relapse-free. During the double-blind treatment phase, the most common adverse events that were more frequent in the fenebrutinib group than in the placebo group were hepatic enzyme elevations (four [6%] vs 0), headache (three [4%] vs one [3%]), and nasopharyngitis (two [3%] vs 0); no serious adverse events or deaths occurred. Interpretation Fenebrutinib was well tolerated and exerted an early, robust, and sustained effect of limiting new focal brain lesions. Further studies are needed to better characterise the safety and efficacy of fenebrutinib on both relapsing multiple sclerosis and non-relapsing progressive multiple sclerosis. Funding F. Hoffmann-La Roche. Copyright (c) 2025 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.

Název v anglickém jazyce

Safety and efficacy of fenebrutinib in relapsing multiple sclerosis (FENopta): a multicentre, double-blind, randomised, placebo-controlled, phase 2 trial and open-label extension study

Popis výsledku anglicky

Background The prospect for Bruton&apos;s tyrosine kinase (BTK) inhibition to meaningfully affect relapsing multiple sclerosis has recently been questioned due to inconsistent findings in the magnitude and sustainability of the effect of BTK inhibitors on disease activity. We assessed the safety, efficacy, and CSF drug concentrations of fenebrutinib, a highly selective, noncovalent, reversible BTK inhibitor, in patients with relapsing multiple sclerosis. Methods This multicentre, double-blind, randomised, placebo-controlled, phase 2 trial (FENopta) was conducted at 18 community centres and hospitals across six countries in Europe and North America. Patients with relapsing multiple sclerosis aged 18-55 years with an Expanded Disability Status Scale (EDSS) score of 0&lt;middle dot&gt;0-5&lt;middle dot&gt;5, and recent documented disease activity, were randomly assigned (2:1) to oral fenebrutinib (200 mg twice daily) or placebo for 12 weeks, using permuted blocks and stratified by the presence or absence of T1 gadolinium-enhancing (Gd+) lesions on the brain MRI at screening. The randomisation sequence was generated by an interactive voice or web response system and both patients and investigators were masked to treatment allocation. Participants could enter an optional open-label extension study to receive fenebrutinib for up to 192 weeks. The primary efficacy endpoint was the total number of new T1 Gd+ lesions on brain MRI at weeks 4, 8, and 12; with additional MRI assessments at 48-week intervals during the open-label extension. Efficacy analyses were done on randomised patients with evaluable post-baseline MRIs; safety analyses used the safety-evaluable population. This study is registered with ClinicalTrials.gov, NCT05119569, and EudraCT, 2021-003772-14; recruitment is closed and the trial is ongoing. Findings Between March 1, 2022 and March 29, 2023, 109 patients with relapsing multiple sclerosis were randomly assigned treatment: 73 received fenebrutinib and 36 received placebo. 106 patients had evaluable post-baseline brain MRI scans and were assessed for efficacy in the fenebrutinib group (n=70) and placebo group (n=36). The combined number of new T1 Gd+ lesions at weeks 4, 8, and 12 were 0&lt;middle dot&gt;077 (95% CI 0&lt;middle dot&gt;043-0&lt;middle dot&gt;135) in the fenebrutinib group and 0&lt;middle dot&gt;245 (0&lt;middle dot&gt;144-0&lt;middle dot&gt;418) in the placebo group (69% relative reduction [95% CI 34-85]; p=0&lt;middle dot&gt;0022). During the open-label extension, through week 48, the unadjusted annualised relapse rate was 0&lt;middle dot&gt;04 and 95 (96%) of 99 patients were relapse-free. During the double-blind treatment phase, the most common adverse events that were more frequent in the fenebrutinib group than in the placebo group were hepatic enzyme elevations (four [6%] vs 0), headache (three [4%] vs one [3%]), and nasopharyngitis (two [3%] vs 0); no serious adverse events or deaths occurred. Interpretation Fenebrutinib was well tolerated and exerted an early, robust, and sustained effect of limiting new focal brain lesions. Further studies are needed to better characterise the safety and efficacy of fenebrutinib on both relapsing multiple sclerosis and non-relapsing progressive multiple sclerosis. Funding F. Hoffmann-La Roche. Copyright (c) 2025 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30210 - Clinical neurology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Lancet Neurology

ISSN

1474-4422

e-ISSN

1474-4465

Svazek periodika

24

Číslo periodika v rámci svazku

8

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

11

Strana od-do

656-666

Kód UT WoS článku

001536709600001

EID výsledku v databázi Scopus

—