Regulus Therapeutics Announces Completion of Enrollment in Fourth Cohort of Phase 1b Multiple-Ascending Dose (MAD) Clinical Trial of RGLS8429 for the Treatment of Patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD)
Regulus Therapeutics (Nasdaq: RGLS) has completed enrollment of 26 patients in the fourth cohort of its Phase 1b Multiple-Ascending Dose (MAD) clinical trial for RGLS8429, targeting Autosomal Dominant Polycystic Kidney Disease (ADPKD). The study has shown positive results from previous cohorts, demonstrating a mechanistic dose response based on increased urinary polycystins (PC1 and PC2). Exploratory imaging analysis revealed mean reductions in height adjusted total kidney volume (htTKV). The company plans an End of Phase 1 meeting with the FDA by the end of 2024 and expects to share topline data from cohort four in early 2025. The Phase 1b MAD study is evaluating safety, tolerability, and pharmacokinetics/pharmacodynamics of RGLS8429 across different dose levels in ADPKD patients.
Regulus Therapeutics (Nasdaq: RGLS) ha completato l'arruolamento di 26 pazienti nella quarta coorte del suo studio clinico di Fase 1b Multiple-Ascending Dose (MAD) per RGLS8429, mirato a Malattia Cistica Renale Autosomica Dominante (ADPKD). Lo studio ha mostrato risultati positivi dalle coorti precedenti, dimostrando una risposta meccanica alla dose basata sull'aumento delle policistine urinarie (PC1 e PC2). Un'analisi di imaging esplorativa ha rivelato riduzioni medie nel volume totale dei reni aggiustato per altezza (htTKV). L'azienda prevede un incontro di fine Fase 1 con la FDA entro la fine del 2024 e si aspetta di condividere i dati preliminari della quarta coorte all'inizio del 2025. Lo studio di Fase 1b MAD sta valutando la safety, tollerabilità e farmacocinetica/farmacodinamica di RGLS8429 a diversi livelli di dose nei pazienti con ADPKD.
Regulus Therapeutics (Nasdaq: RGLS) ha completado la inclusión de 26 pacientes en la cuarta cohorte de su ensayo clínico de Fase 1b Multiple-Ascending Dose (MAD) para RGLS8429, dirigido a Enfermedad Quística Renal Autosómica Dominante (ADPKD). El estudio ha mostrado resultados positivos de cohorte anteriores, demostrando una respuesta mecánica a la dosificación basada en el aumento de policistinas urinarias (PC1 y PC2). Un análisis de imagen exploratorio reveló reducciones medias en el volumen total del riñón ajustado por altura (htTKV). La empresa planea una reunión de fin de Fase 1 con la FDA para finales de 2024 y espera compartir datos preliminares de la cuarta cohorte a principios de 2025. El estudio MAD de Fase 1b está evaluando la seguridad, tolerabilidad y farmacocinética/farmacodinámica de RGLS8429 a diferentes niveles de dosificación en pacientes con ADPKD.
레귤러스 테라퓨틱스(Nasdaq: RGLS)는 26명의 환자 등록을 완료했습니다, 네 번째 코호트에 관한 1b상 다중 증가 용량(MAD) 임상 시험에서 RGLS8429를 대상으로 하는 유전적 다낭성 신장 질환 (ADPKD). 이 연구는 이전 코호트로부터 긍정적인 결과를 보여주었으며, 이는 소변 내 폴리시스틴(PC1 및 PC2)의 증가에 따라 기전적 용량 반응을 입증하고 있습니다. 탐색적 영상 분석에서는 신장 부피의 높이 조정 평균 감소(htTKV)가 나타났습니다. 이 회사는 2024년 말까지 FDA와 1단계 종료 회의를 예정하고 있으며, 2025년 초에는 네 번째 코호트의 전체 데이터를 공유할 것으로 기대하고 있습니다. 1b상 MAD 연구는 ADPKD 환자에 대한 RGLS8429의 안전성, 내약성 및 약리학적 작용/약물 동역학을 다양한 용량 수준에서 평가하고 있습니다.
Regulus Therapeutics (Nasdaq: RGLS) a terminé l'enrôlement de 26 patients dans la quatrième cohorte de son essai clinique de Phase 1b Multiple-Ascending Dose (MAD) pour le RGLS8429, ciblant la maladie polykystique rénale autosomique dominante (ADPKD). L'étude a montré des résultats positifs des cohortes précédentes, démontrant une réaction dose-mécanisme basée sur l'augmentation des polykystines urinaires (PC1 et PC2). Une analyse d'imagerie exploratoire a révélé des diminutions moyennes du volume total des reins ajusté à la hauteur (htTKV). La société prévoit une réunion de fin de phase 1 avec la FDA d'ici la fin de 2024 et s'attend à partager les données préliminaires de la quatrième cohorte au début de 2025. L'étude MAD de phase 1b évalue la santé, la tolérabilité et la pharmacocinétique/pharmacodynamique de RGLS8429 à différents niveaux de dose chez les patients atteints de ADPKD.
Regulus Therapeutics (Nasdaq: RGLS) hat die Einschreibung von 26 Patienten in der vierten Kohorte seiner Phase 1b Multiple-Ascending Dose (MAD) klinischen Studie für RGLS8429, die Autosomal-Dominante Zystenniere (ADPKD) anvisiert, abgeschlossen. Die Studie hat positive Ergebnisse aus vorherigen Kohorten gezeigt, die eine mechanistische Dosis-Antwort basierend auf erhöhten urinaren Polycystinen (PC1 und PC2) demonstrieren. Eine explorative Bildanalyse ergab durchschnittliche Reduktionen des höhenadjustierten Gesamtniervolumens (htTKV). Das Unternehmen plant ein Meeting zum Ende von Phase 1 mit der FDA bis Ende 2024 und erwartet, die toplin Daten von Kohorte vier Anfang 2025 zu teilen. Die Phase 1b MAD Studie bewertet die Sicherheit, Verträglichkeit und Pharmakokinetik/Pharmakodynamik von RGLS8429 über verschiedene Dosen bei ADPKD-Patienten.
- Completed enrollment of 26 patients in the fourth cohort of Phase 1b MAD study
- Positive results from previous cohorts showing mechanistic dose response
- Mean reductions observed in height adjusted total kidney volume (htTKV)
- On track for End of Phase 1 meeting with FDA by end of 2024
- Topline data from cohort four expected in early 2025
- None.
Insights
The completion of enrollment in the fourth cohort of Regulus Therapeutics' Phase 1b MAD study for RGLS8429 is a significant milestone in the development of a potential treatment for ADPKD. The study has shown promising results so far, with evidence of a mechanistic dose response based on increased urinary polycystins (PC1 and PC2) across cohorts. This is important as these proteins inversely correlate with disease severity.
The exploratory imaging analysis revealing mean reductions in height-adjusted total kidney volume (htTKV) is particularly noteworthy. htTKV is a key biomarker for ADPKD progression and its reduction could indicate potential disease-modifying effects. The fixed 300 mg dose in the fourth cohort will provide important data on efficacy and safety at this level.
With the End of Phase 1 meeting with the FDA planned by the end of 2024 and topline data from cohort four expected in early 2025, Regulus is positioning itself for a potential pivotal Phase 3 trial. This progress is encouraging for ADPKD patients, who currently have treatment options. However, investors should remain cautious as Phase 1b results, while promising, do not guarantee success in later-stage trials or ultimate FDA approval.
The completion of enrollment in the final cohort of Regulus Therapeutics' Phase 1b study for RGLS8429 is a positive development for the company's pipeline. With a
Key financial considerations include:
- Potential for accelerated development timeline if data remains positive
- Possible increase in investor interest as the company approaches the End of Phase 1 meeting with the FDA
- Potential for partnerships or licensing deals if RGLS8429 continues to show promise
- Need for additional funding to support a Phase 3 trial, which could lead to dilution for current shareholders
The ADPKD market represents a significant opportunity, with current treatments. If RGLS8429 demonstrates efficacy and safety in later-stage trials, it could capture a substantial market share. However, investors should be aware of the high risk associated with early-stage biotech companies and the potential for volatility based on clinical trial results.
"The completion of enrollment of our final cohort marks an important milestone as we near the end of our Phase 1b study. We have been pleased to see positive results from each of the prior three cohorts, showing continued evidence of a mechanistic dose response based on increase in urinary polycystins (PC1 and PC2), across cohorts. Additionally, exploratory imaging analysis has shown mean reductions in height adjusted total kidney volume (htTKV), a key measurement which we will be evaluating in the fourth cohort and in the potentially pivotal Phase 3 trial," said Jay Hagan, CEO of Regulus. "We remain on track for an End of Phase 1 meeting with the FDA by the end of 2024, and we plan to share topline data from a substantial number of patients in cohort four in early 2025."
The Phase 1b MAD study is a double-blind, placebo-controlled, weight-based dosing and an open-label fixed dose trial evaluating the safety, tolerability, pharmacokinetics and pharmacodynamics (PK/PD) of RGLS8429 in adult patients with ADPKD. The study is evaluating RGLS8429 treatment across three different weight-based dose levels (cohort 1-3) and one fixed dose level (cohort 4), including measuring changes in urinary polycystins PC1 and PC2, height adjusted total kidney volume (htTKV), cyst architecture, and overall kidney function. PC1 and PC2 are the protein products of the PKD1 and PKD2 genes and have been shown to inversely correlate with disease severity. Patients in the fourth cohort are receiving a fixed dose of 300 mg of RGLS8429 administered every other week for three months.
More information about the MAD clinical trial is available at clinicaltrials.gov (NCT05521191).
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 RGLS8429
RGLS8429 is a novel, next generation oligonucleotide for the treatment of ADPKD designed to inhibit miR-17 and to preferentially target the kidney. Administration of RGLS8429 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 RGLS8429 has a favorable safety and PK profile. RGLS8429 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 and from the third cohort of patients in June 2024. Regulus completed enrollment in the fourth cohort of patients in October 2024. Patients in the fourth cohort are receiving a 300 mg fixed dose of RGLS8429 administered every other week for three months.
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
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 RGLS8429 program and preclinical pipeline, the potential that RGLS8429 may be eligible for an Accelerated Approval pathway, potentially achieving therapeutic efficacy and clinical translation for patients, the expected timing for reporting interim or topline data, 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 "believes," "anticipates," "plans," "expects," "intends," "will," "goal," "potential" 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, that 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, the FDA has not designated RGLS8429 for an Accelerated Approval pathway and such designation may not lead to a faster development, regulatory review or approval process and does not increase the likelihood that RGLS8429 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 toxicology 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 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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FAQ
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