Arrowhead Pharmaceuticals Announces Topline Results from Part 2 of Phase 1/2 Study of ARO-C3 in Patients with IgA Nephropathy
Arrowhead Pharmaceuticals (NASDAQ: ARWR) has announced topline results from Part 2 of its Phase 1/2 study of ARO-C3, an RNAi therapeutic targeting complement component 3 (C3) for complement-mediated diseases. The study focused on patients with IgA nephropathy (IgAN).
Key findings from the trial (n=14) include:
- Mean sustained C3 reduction >87% through week 24
- Mean sustained AH50 reduction >76% through week 24
- Mean sustained Wieslab AP reduction >89% through week 24
- Mean reduction in spot UPCR of 41% by week 24, with maximum individual reduction of 89%
The treatment was generally well-tolerated with no serious adverse events reported. The most common side effects were headache, cough, and nasopharyngitis. The duration of effect supports quarterly or less frequent subcutaneous dosing in future studies. Additional results will be presented at a medical meeting in 2025.
Arrowhead Pharmaceuticals (NASDAQ: ARWR) ha annunciato i risultati preliminari della Parte 2 del suo studio di Fase 1/2 su ARO-C3, una terapia RNAi che mira al componente del complemento 3 (C3) per le malattie mediate dal complemento. Lo studio si è concentrato su pazienti con nefropatia da IgA (IgAN).
I risultati chiave della sperimentazione (n=14) includono:
- Riduzione media sostenuta di C3 >87% fino alla settimana 24
- Riduzione media sostenuta di AH50 >76% fino alla settimana 24
- Riduzione media sostenuta di Wieslab AP >89% fino alla settimana 24
- Riduzione media dell'UPCR spot del 41% entro la settimana 24, con una riduzione individuale massima del 89%
Il trattamento è stato generalmente ben tollerato, senza eventi avversi gravi riportati. Gli effetti collaterali più comuni erano mal di testa, tosse e nasofaringite. La durata dell'effetto supporta dosaggi sottocutanei trimestrali o meno frequenti in studi futuri. Ulteriori risultati saranno presentati in un incontro medico nel 2025.
Arrowhead Pharmaceuticals (NASDAQ: ARWR) ha anunciado los resultados preliminares de la Parte 2 de su estudio de Fase 1/2 sobre ARO-C3, una terapia de RNAi que tiene como objetivo el componente del complemento 3 (C3) para enfermedades mediadas por complemento. El estudio se centró en pacientes con nefropatía por IgA (IgAN).
Los hallazgos clave del ensayo (n=14) incluyen:
- Reducción media sostenida de C3 >87% hasta la semana 24
- Reducción media sostenida de AH50 >76% hasta la semana 24
- Reducción media sostenida de Wieslab AP >89% hasta la semana 24
- Reducción media en el UPCR puntual del 41% para la semana 24, con una reducción individual máxima del 89%
El tratamiento fue generalmente bien tolerado, sin eventos adversos graves reportados. Los efectos secundarios más comunes fueron dolor de cabeza, tos y nasofaringitis. La duración del efecto respalda la dosificación subcutánea trimestral o menos frecuente en futuros estudios. Se presentarán resultados adicionales en una reunión médica en 2025.
Arrowhead Pharmaceuticals (NASDAQ: ARWR)는 보체 매개 질환을 위한 보체 성분 3 (C3)을 표적으로 하는 RNAi 치료제 ARO-C3의 1/2상 연구 2부의 주요 결과를 발표했습니다. 이 연구는 IgA 신병증 (IgAN) 환자에 초점을 맞췄습니다.
시험의 주요 결과 (n=14)는 다음과 같습니다:
- 24주까지 C3의 평균 지속적 감소 >87%
- 24주까지 AH50의 평균 지속적 감소 >76%
- 24주까지 Wieslab AP의 평균 지속적 감소 >89%
- 24주까지 스팟 UPCR의 평균 감소 41%, 최대 개인 감소 89%
치료는 일반적으로 잘 견디며 심각한 부작용은 보고되지 않았습니다. 가장 흔한 부작용은 두통, 기침 및 비인두염이었습니다. 효과의 지속 시간은 향후 연구에서 분기별 또는 덜 빈번한 피하 투여를 지원합니다. 추가 결과는 2025년 의료 회의에서 발표될 예정입니다.
Arrowhead Pharmaceuticals (NASDAQ: ARWR) a annoncé les résultats préliminaires de la Partie 2 de son étude de Phase 1/2 sur ARO-C3, une thérapie RNAi ciblant le composant du complément 3 (C3) pour les maladies médiées par le complément. L'étude s'est concentrée sur des patients atteints de néphropathie à IgA (IgAN).
Les résultats clés de l'essai (n=14) comprennent:
- Réduction moyenne soutenue de C3 >87% jusqu'à la semaine 24
- Réduction moyenne soutenue d'AH50 >76% jusqu'à la semaine 24
- Réduction moyenne soutenue de Wieslab AP >89% jusqu'à la semaine 24
- Réduction moyenne de l'UPCR ponctuel de 41% d'ici la semaine 24, avec une réduction individuelle maximale de 89%
Le traitement a été généralement bien toléré, sans événements indésirables graves signalés. Les effets secondaires les plus courants étaient des maux de tête, de la toux et une nasopharyngite. La durée de l'effet soutient une posologie sous-cutanée trimestrielle ou moins fréquente dans les études futures. Des résultats supplémentaires seront présentés lors d'une réunion médicale en 2025.
Arrowhead Pharmaceuticals (NASDAQ: ARWR) hat die vorläufigen Ergebnisse aus Teil 2 seiner Phase 1/2-Studie zu ARO-C3, einer RNAi-Therapie, die auf das Komplementkomponente 3 (C3) für komplementvermittelte Erkrankungen abzielt, bekannt gegeben. Die Studie konzentrierte sich auf Patienten mit IgA-Nephropathie (IgAN).
Wichtige Ergebnisse der Studie (n=14) sind:
- Durchschnittliche nachhaltige C3-Reduktion >87% bis Woche 24
- Durchschnittliche nachhaltige AH50-Reduktion >76% bis Woche 24
- Durchschnittliche nachhaltige Wieslab AP-Reduktion >89% bis Woche 24
- Durchschnittliche Reduktion des Spot UPCR um 41% bis Woche 24, mit maximaler individueller Reduktion von 89%
Die Behandlung wurde im Allgemeinen gut vertragen, es wurden keine schwerwiegenden unerwünschten Ereignisse berichtet. Die häufigsten Nebenwirkungen waren Kopfschmerzen, Husten und Nasopharyngitis. Die Dauer der Wirkung unterstützt eine vierteljährliche oder weniger häufige subkutane Dosierung in zukünftigen Studien. Zusätzliche Ergebnisse werden auf einer medizinischen Tagung im Jahr 2025 präsentiert.
- Strong efficacy with >87% sustained reduction in C3 levels
- Significant 41% mean reduction in proteinuria (UPCR), indicating improved kidney function
- Favorable safety profile with no serious adverse events
- Quarterly dosing potential could offer competitive advantage
- Maximum individual UPCR reduction of 89% demonstrates strong potential in some patients
- Full trial results delayed until 2025 medical meeting
- Small patient sample size (n=14) may limit result interpretation
Insights
Arrowhead's Phase 1/2 data for ARO-C3 in IgA nephropathy (IgAN) demonstrates impressive target engagement with sustained reductions in complement biomarkers - ≥87% for C3, ≥76% for AH50, and ≥89% for Wieslab AP through 24 weeks. This near-complete inhibition of the alternative complement pathway is scientifically significant for this mechanism.
The 41% mean reduction in proteinuria (UPCR) represents meaningful clinical benefit, as proteinuria reduction correlates with improved kidney outcomes in IgAN. For context, this level of proteinuria reduction at 24 weeks is competitive with other developmental IgAN therapies and potentially clinically meaningful if maintained long-term.
The favorable safety profile with no serious adverse events and the convenience of quarterly dosing creates a compelling clinical profile. The RNAi approach to complement inhibition offers potential advantages over antibody-based competitors including Apellis and Novartis in terms of dosing frequency and administration route (subcutaneous vs. intravenous).
These results strongly support advancement to later-stage trials in IgAN, a disease with significant unmet need and few approved therapies beyond blood pressure medications and steroids. The data also validates Arrowhead's platform in complement-mediated diseases beyond this single indication.
These ARO-C3 results represent a potentially significant advancement in IgAN treatment. The 41% proteinuria reduction after just 24 weeks is clinically meaningful, as sustained proteinuria reduction correlates with preserved kidney function and delayed progression to kidney failure in IgAN patients.
The mechanism targeting C3 is particularly interesting for IgAN pathophysiology. In IgAN, galactose-deficient IgA1 antibodies form immune complexes that deposit in kidney glomeruli, activating complement pathways and causing inflammation and scarring. By inhibiting C3, ARO-C3 targets a central node in this pathogenic cascade.
The efficiency of once-quarterly dosing would represent a substantial improvement over daily oral medications or more frequent infusions required by other therapies. Moreover, the absence of serious infections - particularly encapsulated organisms which are a concern with complement inhibition - is reassuring from a safety perspective.
What's particularly compelling is that these results were achieved in just 14 patients, suggesting a robust treatment effect. If confirmed in larger studies, ARO-C3 could potentially address the underlying pathophysiology of IgAN rather than just managing symptoms, which would represent a paradigm shift in treatment approach for a disease that remains the leading cause of primary glomerulonephritis worldwide.
- ARO-C3 achieved deep and sustained reductions in alternative pathway complement activity and proteinuria
- Mean sustained reductions in C3 of ≥
- Mean reduction in spot urine protein-to-creatinine ratio (UPCR) of
Select Phase 1/2 Study Results
- Patients with IgA nephropathy (IgAN) (n=14) received subcutaneous doses of ARO-C3 (400 mg) on Days 1, 29, and 113 and were followed through Day 169
-
Pharmacodynamic effects
-
Maximum mean reduction in C3 of
89% and mean sustained reduction of greater than87% from baseline through week 24 -
Maximum mean reduction in serum AH50 (alternative pathway hemolytic assay) of
85% and mean sustained reduction greater than76% from baseline through week 24 -
Maximum mean reduction in Wieslab AP (alternative pathway) of
100% and mean sustained reduction greater than89% from baseline through week 24 - Duration of effect supportive of once every three month or less frequent subcutaneous dosing in later stage studies
-
Maximum mean reduction in C3 of
-
Effects on proteinuria
-
Mean reduction in spot UPCR of
41% and maximum individual reduction of89% from baseline by week 24
-
Mean reduction in spot UPCR of
-
Safety and Tolerability
- ARO-C3 was generally well-tolerated in patients with IgAN
- No serious or severe treatment emergent adverse events (TEAE) and no TEAEs that led to study or study drug discontinuation
- The only TEAEs reported in more than 1 subject were headache, cough, and nasopharyngitis
- No infections with encapsulated organisms
“ARO-C3 has shown potent and consistent results in normal healthy volunteers and now in patients with IgA nephropathy, including up to
About ARO-C3
ARO-C3 is designed to reduce hepatocyte production of complement component 3 (C3) as a potential treatment for various complement mediated renal diseases. Dysregulated activity of the complement system can play a primary pathogenic role and can contribute to tissue injury and progression of disease. By silencing C3, investigational ARO-C3 has the potential to treat complement-mediated renal diseases by modulating activation of the complement cascade.
About the AROC3-1001 Phase 1/2a Study
AROC3-1001 (NCT05083364) is a Phase 1/2a first-in-human dose-escalating study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics in adult healthy volunteers (HVs) and in adult patients with complement-mediated renal disease. In Part 1 of the study, HVs receive either one or two doses of ARO-C3 or placebo. In Part 2 of the study, adult patients with C3 Glomerulopathy (C3G) and IgA Nephropathy (IgAN) receive 3 open-label doses of ARO-C3.
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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