Arrowhead Pharmaceuticals Presents Interim Clinical Data on ARO-CFB for the Treatment of Complement Mediated Diseases
Arrowhead Pharmaceuticals (NASDAQ: ARWR) announced interim results from their Phase 1/2a clinical study of ARO-CFB, an RNAi therapeutic targeting complement factor B for complement mediated diseases. The data, presented at the 8th Complement-Based Drug Development Summit, showed significant efficacy with:
- Up to 90% reduction in circulating CFB protein with over 3 months duration
- Near complete inhibition of alternative pathway activity (100% mean reduction) at 200mg and 400mg doses
- Generally well-tolerated safety profile with mostly mild adverse events
The company plans to complete Part 1 of the study and proceed to Part 2, focusing on patients with immunoglobulin A nephropathy, the most common glomerular disease worldwide.
Arrowhead Pharmaceuticals (NASDAQ: ARWR) ha annunciato risultati intermedi dal loro studio clinico di fase 1/2a di ARO-CFB, una terapia RNAi mirata al fattore B del complemento per le malattie mediate dal complemento. I dati, presentati all'8° Summit sullo Sviluppo di Farmaci Basati sul Complemento, hanno mostrato un'efficacia significativa con:
- Fino al 90% di riduzione della proteina CFB circolante per oltre 3 mesi
- Inibizione quasi completa dell'attività della via alternativa (riduzione media del 100%) a dosi di 200mg e 400mg
- Profilo di sicurezza generalmente ben tollerato con eventi avversi per lo più lievi
L'azienda prevede di completare la Parte 1 dello studio e procedere alla Parte 2, focalizzandosi su pazienti con nefrite da immunoglobulina A, la malattia glomerulare più comune al mondo.
Arrowhead Pharmaceuticals (NASDAQ: ARWR) anunció resultados intermedios de su estudio clínico de fase 1/2a de ARO-CFB, una terapia de RNAi dirigida al factor B del complemento para enfermedades mediadas por complemento. Los datos, presentados en la 8ª Cumbre sobre el Desarrollo de Medicamentos Basados en Complemento, mostraron una eficacia significativa con:
- Reducción de hasta el 90% de la proteína CFB circulante con más de 3 meses de duración
- Inhibición casi completa de la actividad de la vía alternativa (reducción media del 100%) a dosis de 200mg y 400mg
- Perfil de seguridad generalmente bien tolerado con eventos adversos mayormente leves
La empresa planea completar la Parte 1 del estudio y proceder a la Parte 2, centrándose en pacientes con nefropatía por inmunoglobulina A, la enfermedad glomerular más común en el mundo.
애로우헤드 제약(나스닥: ARWR)은 보체 매개 질병을 위한 보체 인자 B를 표적하는 RNAi 치료제 ARO-CFB에 대한 1/2a 단계 임상 연구의 중간 결과를 발표했습니다. 데이터는 제8회 보체 기반 약물 개발 정상 회의에서 발표되었으며, 다음과 같은 유의미한 효능을 보여주었습니다:
- 3개월 이상 지속되는 CFB 단백질의 순환에서 최대 90% 감소
- 200mg 및 400mg 용량에서 대체 경로 활동의 거의 완전 억제 (평균 100% 감소)
- 대부분 가벼운 부작용으로 일반적으로 잘 견딜 수 있는 안전성 프로필
회사는 연구 1부를 완료하고 2부로 진행할 계획이며, 세계에서 가장 흔한 사구체 질환인 면역글로불린 A 신병증 환자에 집중할 것입니다.
Arrowhead Pharmaceuticals (NASDAQ: ARWR) a annoncé des résultats intermédiaires de son étude clinique de phase 1/2a sur l'ARO-CFB, une thérapie RNAi ciblant le facteur B du complément pour les maladies médiées par le complément. Les données, présentées lors du 8ème Sommet sur le Développement de Médicaments Basés sur le Complément, ont montré une efficacité significative avec :
- Réduction de jusqu'à 90% de la protéine CFB circulante durant plus de 3 mois
- Inhibition presque complète de l'activité de la voie alternative (réduction moyenne de 100%) à des doses de 200mg et 400mg
- Profil de sécurité généralement bien toléré avec surtout des effets indésirables légers
L'entreprise prévoit de compléter la Partie 1 de l'étude et de passer à la Partie 2, en se concentrant sur les patients atteints de néphropathie à immunoglobuline A, la maladie glomérulaire la plus répandue dans le monde.
Arrowhead Pharmaceuticals (NASDAQ: ARWR) hat vorläufige Ergebnisse aus ihrer Phase 1/2a-Studie zu ARO-CFB bekanntgegeben, einer RNAi-Therapie, die auf das Komplementfaktor B für komplementvermittelte Krankheiten abzielt. Die Daten, die auf dem 8. Gipfel zur Entwicklung von komplementbasierten Arzneimitteln vorgestellt wurden, zeigten eine signifikante Wirksamkeit mit:
- Bis zu 90% Reduktion des zirkulierenden CFB-Proteins über mehr als 3 Monate
- Nahezu vollständige Hemmung der Aktivität des alternativen Weges (Durchschnittsreduktion von 100%) bei 200mg und 400mg Dosen
- Allgemein gut verträgliches Sicherheitsprofil mit überwiegend milden Nebenwirkungen
Das Unternehmen plant, Teil 1 der Studie abzuschließen und zu Teil 2 überzugehen, wobei der Fokus auf Patienten mit einer IgA-Nephropathie liegt, der weltweit häufigsten glomerulären Erkrankung.
- Achieved 90% reduction in CFB protein levels with single 400mg dose
- Demonstrated 100% mean reduction in alternative pathway activity by week 4
- Treatment effects showed duration greater than 3 months
- Safety profile shows good tolerability with mostly mild adverse events
- No treatment discontinuations due to adverse events
- None.
Insights
The interim Phase 1/2a data for ARO-CFB demonstrates remarkable efficacy in complement system modulation. The 90% reduction in circulating CFB protein and near-complete inhibition of alternative pathway activity are exceptional results that exceed typical early-phase expectations. The durability of effect lasting >3 months from a single dose is particularly noteworthy, suggesting potential for quarterly dosing regimens. The clean safety profile with mostly mild TEAEs and no discontinuations strengthens the therapeutic potential.
The progression to IgA nephropathy patients in Part 2 is strategically sound, as complement dysregulation is a key disease driver. If similar efficacy is demonstrated in patients, ARO-CFB could become a significant player in the
These compelling interim results significantly de-risk ARO-CFB's development program and enhance Arrowhead's position in the lucrative complement therapeutics space. The robust efficacy data, particularly the 100% reduction in alternative pathway activity at multiple dose levels, suggests potential best-in-class attributes. The favorable durability profile could translate to competitive advantages in pricing and market adoption.
For Arrowhead's
- Interim data from Phase 1/2a study demonstrate near complete inhibition in hemolytic activity and functional activity of alternative complement pathway
“Dysregulated activation of the complement system can lead to progression of certain renal diseases, either by playing a directly pathogenic role, or by amplifying or exacerbating the inflammatory and damaging impact of non-complement disease triggers. In a Phase 1/2a clinical study, ARO-CFB treatment in healthy volunteers achieved deep and durable reductions in the liver production of complement factor B (CFB), which is involved in alternative complement pathway activation and associated with pathogenesis of diseases involving complement activation. Circulating levels of CFB protein were reduced by a mean of up to
Select ARO-CFB Results
In the ongoing AROCFB-1001 study, ARO-CFB achieved the following key results in normal healthy volunteers as of the interim data cutoff - 15 November 2024:
-
ARO-CFB led to dose dependent reductions in circulating CFB protein by up to
90% with greater than 3 months duration-
90% mean reduction achieved after a single dose of 400 mg -
90% mean reduction achieved after two doses of 100 mg
-
-
Single and multiple doses of ARO-CFB led to near complete inhibition of alternative pathway activity based on Wieslab AP
-
100% mean reduction achieved by week 4 after a single dose at both 200 mg and 400 mg doses -
92% and100% mean reductions were achieved after two doses at 100 mg and 200 mg, respectively
-
- Single and multiple doses of ARO-CFB led to near complete inhibition of alternative pathway hemolytic activity, measured by AH50
Safety and Tolerability Results
ARO-CFB has been generally well-tolerated to date with safety data supportive of further clinical development. There have been no treatment emergent adverse events (TEAE) leading to study or study drug discontinuation with most TEAEs being mild in severity.
About ARO-CFB
ARO-CFB is designed to reduce hepatic expression of complement factor B (CFB), which plays an important regulatory role in amplifying complement alternative pathway activation and has been identified as a promising therapeutic target. ARO-CFB is being developed as a potential treatment for complement mediated kidney diseases such as immunoglobulin A nephropathy (IgAN), which is the most common glomerular disease worldwide and carries a high lifetime risk of progression to end-stage renal disease. Additionally, ARO-CFB may have clinical applications in non-renal diseases involving complement activation.
About the AROCFB-1001 Phase 1/2 Study
AROCFB-1001 (NCT06209177) is an ongoing Phase 1/2a dose-escalating study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of ARO-CFB in up to 66 normal healthy volunteers (NHV) and patients with complement mediated kidney disease. In Part 1 of the study, NHVs will receive either one or two doses of ARO-CFB or placebo. In Part 2 of the study, adult patients with IgAN will receive 3 open-label doses of ARO-CFB. The study is designed to assess safety and tolerability and key pharmacodynamic parameters, including the change and percent change from baseline over time in serum CFB, and alternative complement pathway activity via AH50 and Wieslab AP.
About Arrowhead Pharmaceuticals
Arrowhead Pharmaceuticals develops medicines that treat intractable diseases by silencing the genes that cause them. Using a broad portfolio of RNA chemistries and efficient modes of delivery, Arrowhead therapies trigger the RNA interference mechanism to induce rapid, deep, and durable knockdown of target genes. RNA interference, or RNAi, is a mechanism present in living cells that inhibits the expression of a specific gene, thereby affecting the production of a specific protein. Arrowhead’s RNAi-based therapeutics leverage this natural pathway of gene silencing.
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Source: Arrowhead Pharmaceuticals, Inc.
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Arrowhead Pharmaceuticals, Inc.
Vince Anzalone, CFA
626-304-3400
ir@arrowheadpharma.com
Investors:
LifeSci Advisors, LLC
Brian Ritchie
212-915-2578
britchie@lifesciadvisors.com
Media:
LifeSci Communications, LLC
Kendy Guarinoni, Ph.D.
724-910-9389
kguarinoni@lifescicomms.com
Source: Arrowhead Pharmaceuticals, Inc.
FAQ
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