Delving into the Latest Updates on RO-706293 with Synapse

Overview

Basic Info

Drug Type

ASO

Synonyms

Target-

Mechanism

RNA interference, Virus replication inhibitors

Therapeutic Areas

Infectious DiseasesDigestive System Disorders

Active Indication-

Inactive Indication

Hepatitis BHepatitis B, Chronic

Originator Organization

F. Hoffmann-La Roche Ltd.

Active Organization-

Inactive Organization

Hoffmann-La Roche, Inc.

Roche Diagnostics (Shanghai) Co., Ltd.F. Hoffmann-La Roche Ltd.

+ [1]

Drug Highest PhasePendingPhase 1

First Approval Date-

Regulation-

Login to view timeline

Structure

Boost your research with our RNA technology data.

login

or

view full example data

Boost your research with our RNA technology data.

A Randomized, Sponsor-Open, Placebo-Controlled Study to Evaluate Safety, Tolerability and Pharmacokinetics and Pharmacodynamics of Subcutaneous Administration of RO7062931 With Single Ascending Doses in Healthy Volunteers and Multiple Doses and Modified Regimens in Virologically Suppressed Patients With Chronic Hepatitis B Virus Infection

This randomized study will be conducted in two parts to evaluate the safety, tolerability, pharmacodynamics, and pharmacokinetics of subcutaneous administration of RO7062931. Part 1 will include only healthy participants and Part 2 will include only participants with chronic hepatitis B (CHB). Part 1 is an adaptive, single-ascending dose study with an adaptive dose-escalating schedule to determine the best dose to be evaluated in participants with CHB. Part 2 is an adaptive, parallel multiple-dose study comprised of three sub-parts which will be used to further refine the dose and dosing regimen, and to evaluate the safety and efficacy of RO7062931 when administered with standard-of-care (SoC) therapy.

Start Date06 Feb 2017

Sponsor / Collaborator

Hoffmann-La Roche, Inc.

100 Clinical Results associated with RO-706293

Login to view more data

100 Translational Medicine associated with RO-706293

Login to view more data

100 Patents (Medical) associated with RO-706293

Login to view more data

5

Literatures (Medical) associated with RO-706293

01 Jul 2023·Clinical and translational science

A single ascending dose study of single-stranded oligodeoxyribonucleotide RO7062931 in Chinese healthy volunteers.

Article

Author: Cheung, Tsang Tommy ; Luk, Andrea On Yan ; Zhang, Yuchen ; Pavlovic, Vedran ; Das, Sudip ; Grippo, Joseph F. ; Wat, Cynthia ; Triyatni, Miriam ; Surujbally, Bernadette

RO7062931 is an N-acetylgalactosamine (GalNAc)-conjugated single-stranded oligodeoxyribonucleotide complementary to hepatitis B virus RNA.GalNAc conjugation targets the liver through the asialoglycoprotein receptor (ASGPR).This phase I single ascending dose (SAD) study evaluated the safety, tolerability, and pharmacokinetics of RO7062931 in Chinese healthy volunteers.There were four SAD cohorts (0.3, 1.0, 2.0, and 4.0 mg/kg), in each of which healthy volunteers were randomized to a single s.c. (s.c.) injection of RO7062931 or matching placebo in a 4:1 ratio.Placebo recipients were pooled as one treatment group for safety assessments.A total of 41 healthy Chinese men received one dose of RO7062931 (n = 33) or placebo (n = 8) and completed the study (85-day follow-up).Adverse events (AEs) were reported in 22 of 33 (66.6%) RO7062931 recipients (n = 80 treatment-related) and seven of eight (87.5%) placebo recipients (n = 1 treatment-related).Apart from two moderate-intensity AEs, all AEs were mild.The most frequently reported AEs were influenza, injection-related reactions, and headache.Dose-proportional increases in plasma RO7062931 exposure were observed between the 0.3 and 1.0 mg/kg doses, whereas a supra-dose-proportional increase occurred at doses greater than or equal to 2.0 mg/kg, along with a marked increase in urinary excretion.Single s.c. dose of RO7062931 up to 4.0 mg/kg were safe and well-tolerated in healthy Chinese volunteers.Pharmacokinetic data suggested that ASGPR saturation had commenced between doses of 2.0 and 4.0 mg/kg.Results were broadly consistent with observations in primarily White subjects in the global first-in-human study of RO7062931.

20 Feb 2023·Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology

[Antisense oligodeoxynucleotides: the certain but limited efficacy and the uncovering mechanisms for the cure of chronic hepatitis B].

Article

Author: Lu, F M ; Lu, D J ; Li, D Y

Recently, several phase I and phase II clinical trials of antisense oligodeoxynucleotides (ASOs) targeting to the commonly shared conserved sequences of HBV transcripts brought us some promising results. Particularly in the report of phase IIb clinical trial of Bepirovirsen (GSK3228836), approximately 9-10% patients with low baseline serum HBsAg (> 100 IU/ml & < 3 000 IU/ml) achieved functional cure after 24 weeks' of Bepirovirsen treatment. After reviewing the results of other clinical trials, one would be impressed to know that ALG-020572 (Aligos), RO7062931 (Roche) and GSK3389404 (GSK) all failed to sufficiently suppress serum HBsAg expression though the hepatocyte-targeted delivery of these ASOs were enhanced via N-acetyl galactosamine conjugation. Bepirovirsen enabled some patients to achieve sustained disappearance of serum HBsAg. The analysis of its distribution in different tissues of patients after drug administration showed that only a few fractions of ASOs entered liver tissues and far fewer eventually entered hepatocytes. Taking into consideration that only a few hepatocytes could be expected positive for HBsAg staining among these participants with low serum HBsAg level. We suspect that the mechanistic contribution of ASOs declining the serum HBsAg is not only via directly acting on the HBV transcripts in hepatocytes, but also via entering non-parenchymal cells such as Kupffer cells and resulting in stimulation and activation of innate immunity. Eventually the serum HBsAg declines in most participants and even disappears in a small fraction of patients with low baseline HBsAg level, via attack the infected hepatocytes evidenced by the aberrant elevation of ALT. Nevertheless, the functional cure of CHB remains a challenging issue and more efforts are needed.

01 Apr 2022·Hepatology

Reply

Letter

Author: Wat, Cynthia ; Pavlovic, Vedran ; Grippo, Joseph F. ; Mueller, Henrik ; Gane, Edward ; Krippendorff, Ben‐Fillippo ; Yuen, Man‐Fung ; Ottosen, Soren

Firstly, Dr Vaillant proposes RO7062931 should have exhibited greater HBsAg reductions, given the efficient RO7062931 liver uptake, rapid turnover of HBsAg, and rapid protein reductions observed with GalNAc-ASOs in other therapeutic indications. We find this reasoning unsatisfactory, primarily as there should be no expectations of similar potency for GalNAc-ASOs targeting different mRNA species.

100 Deals associated with RO-706293

Login to view more data

R&D Status

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Hepatitis B	Phase 1	CN	Roche Holding AG	20 Apr 2017
Hepatitis B, Chronic	Phase 1	AU	Hoffmann-La Roche, Inc.	06 Feb 2017
Hepatitis B, Chronic	Phase 1	HK	Hoffmann-La Roche, Inc.	06 Feb 2017
Hepatitis B, Chronic	Phase 1	SG	Hoffmann-La Roche, Inc.	06 Feb 2017
Hepatitis B, Chronic	Phase 1	NZ	Hoffmann-La Roche, Inc.	06 Feb 2017
Hepatitis B, Chronic	Phase 1	TH	Hoffmann-La Roche, Inc.	06 Feb 2017
Hepatitis B, Chronic	Phase 1	KR	Hoffmann-La Roche, Inc.	06 Feb 2017
Hepatitis B, Chronic	Phase 1	TW	Hoffmann-La Roche, Inc.	06 Feb 2017

Login to view more data

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03038113 (Pubmed \| Hepatology)	Phase 1	Hepatitis B, Chronic	119	RO7062931	ohlskfzmcd(ywreccnrtb) = The majority of adverse events (AEs) reported were mild in intensity yxcmibwgwi (sxnfzsjzhf ) View more	-	26 May 2021
NCT03505190 (CTgov)	Phase 1	-	41	Placebo+RO7062931 (RO7062931 0.3mg/kg)	(tlcxmmzdbd) = aojmhcoevu likoyjjeti (hbwvyvttma, tnylsfmpnq - icmrhdfumr) View more	-	03 Aug 2020
NCT03505190 (CTgov)	Phase 1	-	41	Placebo+RO7062931 (RO7062931 1.0mg/kg)	(tlcxmmzdbd) = jpctiqiduc likoyjjeti (hbwvyvttma, fjwrgcjutf - fupvfxeuwy) View more	-	03 Aug 2020