Regulus Therapeutics Announces Positive Clinical and Regulatory Updates from its Autosomal Dominant Polycystic Kidney Disease (ADPKD) Program for Farabursen (RGLS8429)
Regulus Therapeutics announced positive updates for its ADPKD treatment program with farabursen (RGLS8429). The fourth cohort of the Phase 1b Multiple-Ascending Dose study, involving 26 subjects receiving 300mg fixed doses, showed promising results. An interim analysis of 14 subjects demonstrated continued mechanistic dose response and notable reduction in height-adjusted total kidney volume (htTKV) growth rate.
The company also reported a successful End-of-Phase 1 meeting with the FDA, reaching agreement on key components for a Phase 3 single pivotal trial. The trial design includes a 2:1 randomization scheme with placebo, targeting a 12-month htTKV endpoint for potential Accelerated Approval and a 24-month eGFR endpoint for Full Approval.
Safety data from all 26 subjects showed farabursen was well tolerated, with effects on polycystin biomarker levels similar to the previous cohort. The results were consistent across Mayo Imaging Class and PKD1 mutations, with exploratory analyses suggesting high probability of meeting efficacy thresholds.
Regulus Therapeutics ha annunciato aggiornamenti positivi per il suo programma di trattamento dell'ADPKD con farabursen (RGLS8429). La quarta coorte dello studio Fase 1b Multiple-Ascending Dose, che coinvolge 26 soggetti che ricevono dosi fisse di 300 mg, ha mostrato risultati promettenti. Un'analisi intermedia su 14 soggetti ha dimostrato una risposta meccanica dose-dipendente continua e una notevole riduzione del tasso di crescita del volume totale dei reni regolato per altezza (htTKV).
L'azienda ha anche riportato un incontro di successo di Fine Fase 1 con la FDA, raggiungendo un accordo sui componenti chiave per una prova pivotale singola di Fase 3. Il disegno della prova include uno schema di randomizzazione 2:1 con placebo, mirando a un endpoint di htTKV di 12 mesi per una potenziale approvazione accelerata e un endpoint di eGFR di 24 mesi per l'approvazione completa.
I dati di sicurezza provenienti da tutti i 26 soggetti hanno mostrato che farabursen è stato ben tollerato, con effetti sui livelli del biomarcatore della policistina simili a quelli della coorte precedente. I risultati sono stati coerenti attraverso la Classe di Imaging Mayo e le mutazioni di PKD1, con analisi esplorative che suggeriscono un'alta probabilità di raggiungere le soglie di efficacia.
Regulus Therapeutics anunció actualizaciones positivas para su programa de tratamiento de la ADPKD con farabursen (RGLS8429). La cuarta cohorte del estudio de Fase 1b de Dosis Múltiples Ascendentes, que involucra a 26 sujetos que reciben dosis fijas de 300 mg, mostró resultados prometedores. Un análisis intermedio de 14 sujetos demostró una continua respuesta dosis-mecanismo y una notable reducción en la tasa de crecimiento del volumen total del riñón ajustado por altura (htTKV).
La compañía también reportó una reunión exitosa de Fin de Fase 1 con la FDA, alcanzando un acuerdo sobre componentes clave para un ensayo pivotal único de Fase 3. El diseño del ensayo incluye un esquema de randomización 2:1 con placebo, con un objetivo de htTKV de 12 meses para la posible aprobación acelerada y un objetivo de eGFR de 24 meses para la aprobación completa.
Los datos de seguridad de los 26 sujetos mostraron que farabursen fue bien tolerado, con efectos en los niveles de biomarcadores de policistina similares a la cohorte anterior. Los resultados fueron consistentes en la Clase de Imágenes de Mayo y las mutaciones de PKD1, con análisis exploratorios que sugieren una alta probabilidad de cumplir con los umbrales de eficacia.
Regulus Therapeutics는 farabursen(RGLS8429)을 사용한 ADPKD 치료 프로그램에 대한 긍정적인 업데이트를 발표했습니다. 300mg 고정 용량을 받는 26명의 피험자를 포함한 1b상 여러 용량 증가 연구의 네 번째 코호트에서 유망한 결과가 나타났습니다. 14명의 피험자에 대한 중간 분석 결과는 기전적 용량 반응의 지속과 함께 신장의 높이 조정 총체적 부피(htTKV) 성장률의 현저한 감소를 보여주었습니다.
또한 이 회사는 FDA와의 1단계 종료 회의에서 성공적인 합의를 이루었으며, 3단계 단일 주요 시험을 위한 핵심 구성 요소에 대한 의견 일치를 도달했습니다. 시험 설계에는 2:1 비율의 무작위 배정 스킴이 포함되어 있으며, 가속 승인을 위한 12개월 htTKV 목표와 완전 승인을 위한 24개월 eGFR 목표를 설정하고 있습니다.
26명의 피험자 모두에서 수집된 안전성 데이터는 farabursen이 잘 견디는 것으로 나타났으며, 폴리시스틴 바이오마커 수준에 대한 효과는 이전 코호트와 유사했습니다. 결과는 메이요 이미징 클래스와 PKD1 돌연변자 모두에서 일관되었으며, 탐색적 분석은 효능 기준을 충족할 높은 가능성을 시사합니다.
Regulus Therapeutics a annoncé des mises à jour positives pour son programme de traitement de l'ADPKD avec farabursen (RGLS8429). La quatrième cohorte de l'étude de Phase 1b sur les doses multiples ascendantes, impliquant 26 sujets recevant des doses fixes de 300 mg, a montré des résultats prometteurs. Une analyse intermédiaire de 14 sujets a démontré une réponse dose-mécanisme continue et une réduction notable du taux de croissance du volume total des reins ajusté pour la taille (htTKV).
L'entreprise a également rapporté une réunion réussie de Fin de Phase 1 avec la FDA, parvenant à un accord sur des éléments clés pour un essai pivot de Phase 3. Le design de l'essai inclut un schéma de randomisation 2:1 avec placebo, visant un point d'arrivée htTKV de 12 mois pour une éventuelle approbation accélérée et un point d'arrivée eGFR de 24 mois pour une approbation complète.
Les données de sécurité provenant des 26 sujets ont montré que farabursen était bien toléré, avec des effets sur les niveaux de biomarqueurs de la polykystine similaires à ceux de la cohorte précédente. Les résultats étaient cohérents à travers la Classe d'Imagerie Mayo et les mutations PKD1, les analyses exploratoires suggérant une forte probabilité d'atteindre les seuils d'efficacité.
Regulus Therapeutics hat positive Neuigkeiten zu seinem ADPKD-Behandlungsprogramm mit Farabursen (RGLS8429) bekannt gegeben. Die vierte Kohorte der Phase-1b-Studie zu mehrfach steigenden Dosen, die 26 Probanden umfasst, die 300 mg feste Dosen erhalten, zeigte vielversprechende Ergebnisse. Eine interimistische Analyse von 14 Probanden ergab eine kontinuierliche mechanistische Dosis-Wirkungs-Beziehung und eine bemerkenswerte Reduktion der Wachstumsrate des höhenbereinigten gesamten Nierenvolumens (htTKV).
Das Unternehmen berichtete außerdem von einem erfolgreichen Abschluss der Phase-1-Sitzung mit der FDA, bei der Einigung über wichtige Komponenten für eine Phase-3-einzelne Schlüsselstudie erzielt wurde. Das Studiendesign umfasst ein 2:1-Randomisierungsschema mit Placebo, mit dem Ziel, einen 12-monatigen htTKV-Endpunkt für eine potenzielle beschleunigte Genehmigung und einen 24-monatigen eGFR-Endpunkt für die Vollgenehmigung zu erreichen.
Die Sicherheitsdaten aus allen 26 Probanden zeigten, dass Farabursen gut vertragen wurde, mit Auswirkungen auf die Biomarker-Werte der Polyzystin, die mit der vorherigen Kohorte vergleichbar waren. Die Ergebnisse waren in der Mayo Imaging-Klasse und bei PKD1-Mutationen konsistent, wobei explorative Analysen eine hohe Wahrscheinlichkeit daraufhin deuten, die Wirksamkeitsschwellen zu erreichen.
- Positive interim analysis results from Phase 1b trial showing dose response and reduced kidney volume growth
- FDA agreement on Phase 3 trial design with potential for Accelerated Approval pathway
- Consistent safety and tolerability profile across all cohorts
- High probability of meeting efficacy thresholds based on exploratory analyses
- None.
Insights
The latest clinical updates for farabursen (RGLS8429) represent a significant milestone in ADPKD drug development. The fourth cohort data demonstrates two important elements: consistent mechanistic response in urinary polycystin biomarkers and reduction in height-adjusted total kidney volume (htTKV) growth rate. These results are particularly compelling as they show consistency across different Mayo Imaging Classes and PKD1 mutation types.
The FDA's agreement on a single pivotal Phase 3 trial design with potential Accelerated Approval pathway is a major regulatory win. The 12-month htTKV endpoint for Accelerated Approval, followed by 24-month eGFR endpoint for Full Approval, suggests an efficient development timeline. This dual-endpoint strategy aligns with FDA's modern approach to kidney disease drug development, where surrogate endpoints can accelerate patient access while confirming long-term benefits.
The safety profile remains encouraging across all 26 subjects, which is important for a chronic condition like ADPKD where long-term treatment is necessary. The 2:1 randomization scheme in the upcoming Phase 3 trial optimizes statistical power while maintaining ethical considerations for placebo control.
This clinical and regulatory update significantly de-risks Regulus's ADPKD program. The combination of positive biomarker data and FDA alignment on a single pivotal trial pathway potentially accelerates the timeline to market, optimizing development costs and improving the probability of commercial success.
The ADPKD market represents a substantial opportunity, with treatment options currently available. Farabursen's demonstrated safety profile and potential efficacy in reducing kidney volume growth could position it as a compelling treatment option. The microRNA-targeting approach offers a novel mechanism of action, which could provide competitive advantages in this underserved market.
The FDA's acceptance of htTKV as a surrogate endpoint for Accelerated Approval suggests confidence in the program's scientific rationale and clinical relevance. This regulatory pathway could enable faster market entry while collecting confirmatory data, a strategy that has proven successful for other rare disease treatments.
Topline data from an interim analysis of the fourth cohort of its Phase 1b Multiple-Ascending Dose (MAD) clinical trial showed continued mechanistic dose response
Exploratory results of imaging-based biomarkers continued to show reduction in height-adjusted total kidney volume (htTKV) growth rate
Successful End-of-Phase 1 meeting with the
Company to hold conference call at 8:30 a.m. ET today
The Phase 1b MAD study is a double-blind, placebo-controlled trial evaluating the safety, tolerability, pharmacokinetics and pharmacodynamics (PK/PD) of farabursen in adult patients with ADPKD. The study is evaluating farabursen treatment across three different weight-based dose levels and one fixed dose level, including measuring changes in urinary polycystins 1 and 2 (PC1 and PC2), htTKV, and overall kidney function. PC1 and PC2 are the protein products of the PKD1 and PKD2 genes and their levels have been shown to inversely correlate with disease severity.
In the fourth cohort, 26 subjects received a fixed dose of 300 mg of farabursen every other week for three months. An interim analysis of efficacy data from the first 14 subjects of the cohort demonstrated continued evidence of a mechanistic dose response based on urinary PC1 and PC2 levels as well as a notable reduction in htTKV growth rate. In addition, review of complete safety data from all 26 subjects demonstrated farabursen was well tolerated.
Cohort 4 data highlights:
- Effects on polycystin biomarker levels were similar to cohort 3 at 3 mg/kg which is predicted to achieve optimal kidney exposure and resulting miR-17 inhibition
- Exploratory results continue to suggest a notable impact on htTKV growth rate after 3 months of treatment
- htTKV results are consistent across Mayo Imaging Class and PKD1 truncating vs non-truncating mutations
- Exploratory conditional probability analyses suggest high probability of success to meet or exceed targeted htTKV efficacy threshold
- Safety and tolerability profile is encouraging and consistent with earlier cohorts
In December 2024, the Company met with the FDA for an End-of-Phase 1 meeting. Alignment with the FDA was achieved regarding the acceptability of the program's CMC, non-clinical and clinical pharmacology plans and key components of a Phase 3 trial design as a single pivotal study, including:
- A single active dose and placebo administered every other week in a 2:1 randomization scheme
- Key inclusion/exclusion criteria for the trial population
- A 12-month htTKV endpoint for potential Accelerated Approval and a 24-month eGFR endpoint for potential Full Approval
- An acceptable safety database size
"These trial results extend our understanding of the potential benefits and advantages to Regulus' approach in this area of high unmet medical need," said Preston Klassen, M.D., President and Head of Research & Development of Regulus. "Additionally, the data highlight that farabursen appears to be well tolerated, reinforcing its potential as a safe option in the treatment of ADPKD."
"The results from Cohort 4 are very promising, further validating the impact of farabursen on urinary exosomal polycystin levels and suggesting an opportunity to beneficially impact kidney volume growth rate, as we have now observed notable improvements across multiple treatment cohorts," said Alan Yu, M.D., University of Kansas Medical Center. "As Regulus moves into a pivotal study of farabursen, those patients living with ADPKD are one step closer to a potentially safer and more tolerable treatment option."
"Following a productive End-of-Phase 1 meeting with the FDA in December along with the interim results announced today, we are encouraged by the feedback from the agency and are excited about the path forward for farabursen in ADPKD," said Jay Hagan, CEO of Regulus. "The positive results announced today underscore our conviction in the potential of farabursen in ADPKD and we look forward to advancing this program into a pivotal study later this year."
More information about the MAD clinical trial is available at clinicaltrials.gov (NCT05521191).
Conference Call Information
The Company will host a conference call and live audio webcast on Wednesday, January 29 at 8:30 am Eastern Time. To access the call, please dial (833) 816-1394 (domestic) or (412) 317-0487 (international). To access the telephone replay of the call, dial (877) 344-7529 (domestic) or (412) 317-0088 (international), passcode ID 1454429. The webcast and telephone replay will be archived on the Company's website at www.regulusrx.com following the call.
About ADPKD
Autosomal dominant polycystic kidney disease (ADPKD), caused by mutations in the PKD1 or PKD2 genes, is among the most common human monogenic disorders and a leading cause of end-stage renal disease. The disease is characterized by the development of multiple fluid filled cysts primarily in the kidneys, and to a lesser extent in the liver and other organs. Excessive kidney cyst cell proliferation, a central pathological feature, ultimately leads to end-stage renal disease in approximately
About farabursen (RGLS8429)
Farabursen is a novel, next generation oligonucleotide for the treatment of ADPKD designed to inhibit miR-17 and to preferentially target the kidney. Administration of farabursen has shown clear improvements in kidney function, size, and other measures of disease severity in preclinical models. Regulus announced completion of the Phase 1 SAD study in September 2022. The Phase 1 SAD study demonstrated that farabursen has a favorable safety and PK profile. Farabursen was well-tolerated with no serious adverse events reported and plasma exposure was approximately linear across the four doses tested. In the Phase 1b MAD study, Regulus announced topline data from the first cohort of patients in September 2023, from the second cohort of patients in March 2024, from the third cohort of patients in June 2024, and from the first 14 patients from the fourth cohort in January 2025. Patients in the fourth cohort received an open-label 300 mg fixed dose of farabursen which was administered every other week for three months. Review of complete safety data from all cohorts demonstrated that farabursen was well tolerated.
About Regulus
Regulus Therapeutics Inc. (Nasdaq: RGLS) is a biopharmaceutical company focused on the discovery and development of innovative medicines targeting microRNAs. Regulus has leveraged its oligonucleotide drug discovery and development expertise to develop a pipeline complemented by a rich intellectual property estate in the microRNA field. Regulus maintains its corporate headquarters in San Diego, CA.
Forward-Looking Statements
Statements contained in this press release regarding matters that are not historical facts are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including statements associated with the Company's farabursen (RGLS8429) program and preclinical pipeline, the potential that farabursen may be eligible for an Accelerated Approval pathway, predictions based on and future results and outcomes suggested by the Cohort 4 data, our Phase 3 trial design including whether the FDA will ultimately determine its components and the overall design to be acceptable and sufficient to serve as a single pivotal study, the advancing of farabursen into a pivotal study later this year, farabursen potentially being a safe and effective treatment option for ADPKD, and the timing and future occurrence of other preclinical and clinical activities. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Words such as "anticipates," "believes," "expects," "goal," "intends," "look forward to," "plans," "potential," "predict," "suggest," "will" and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon Regulus' current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation: the risk that the approach we are taking to discover and develop drugs is novel and may never lead to marketable products; preliminary or topline results are based on a preliminary analysis of key efficacy and safety data, and such data may change following a more comprehensive review of the data related to the clinical trial and may not be indicative of future results; an Accelerated Approval pathway designation may not be received, or even if it is received, lead to a faster development, regulatory review or approval process, and does not increase the likelihood that farabursen will receive marketing approval; the risk that preclinical and clinical studies may not be successful; risks related to regulatory review and approval; risks related to our reliance on third-party collaborators and other third parties; risks related to intellectual property; risks associated with the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics; the risk that additional data may be negative; and risks related to our ability to successfully secure and deploy capital. These and other risks are described in additional detail in Regulus' filings with the Securities and Exchange Commission, including under the "Risk Factors" heading of Regulus' quarterly report on Form 10-Q for the quarter ended September 30, 2024, available on the Company's website or at www.sec.gov. All forward-looking statements contained in this press release speak only as of the date on which they were made. Regulus undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.
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