obeldesivir (GS-5245) / Gilead - LARVOL DELTA

Study of Obeldesivir as Postexposure Prophylaxis for Marburg Virus Disease (clinicaltrials.gov) - P2 | N=400 | Not yet recruiting | Sponsor: Gilead Sciences

New P2 trial • Infectious Disease

Study of Obeldesivir to Treat Nonhospitalized Adults With Acute Respiratory Syncytial Virus (RSV) Infection (clinicaltrials.gov) - P2 | N=240 | Recruiting | Sponsor: Gilead Sciences | Not yet recruiting ➔ Recruiting

Enrollment open • Infectious Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections

Oral pharmacokinetics and efficacy of oral phospholipid remdesivir nucleoside prodrugs against SARS-CoV-2 in mice. (PubMed, Antimicrob Agents Chemother) - "We previously synthesized 1-O-octadecyl-2-O-benzyl-sn-glyceryl-P-RVn (ODBG-P-RVn, V2043), a phospholipid prodrug of GS-441524 (remdesivir nucleoside, RVn), and demonstrated its in vivo efficacy in a SARS-CoV-2 mouse model. On a molar basis, V2043 and V2067 are substantially more active than obeldesivir/GS-5245 and molnupiravir in vivo. Together, these data support the continued development of phospholipid RVn prodrugs for the treatment of SARS-CoV-2 and other RNA viruses of clinical concern."

Journal • PK/PD data • Preclinical • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Study of Obeldesivir to Treat Nonhospitalized Adults With Acute Respiratory Syncytial Virus (RSV) Infection (clinicaltrials.gov) - P2 | N=240 | Not yet recruiting | Sponsor: Gilead Sciences

New P2 trial • Infectious Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections

The oral nucleoside prodrug GS-5245 is efficacious against SARS-CoV-2 and other endemic, epidemic, and enzootic coronaviruses. (PubMed, Sci Transl Med) - "Here, we characterize the antiviral activity of GS-5245, obeldesivir (ODV), an oral prodrug of the parent nucleoside GS-441524, which targets the highly conserved viral RNA-dependent RNA polymerase (RdRp). Last, we demonstrate that a combination of GS-5245 and main protease (Mpro) inhibitor nirmatrelvir improved outcomes in vivo against SARS-CoV-2 compared with the single agents. Together, our data support the clinical evaluation of GS-5245 against coronaviruses that cause or have the potential to cause human disease."

Journal • Acute Lung Injury • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Study of Obeldesivir in Children and Adolescents With COVID-19 (clinicaltrials.gov) - P2/3 | N=3 | Terminated | Sponsor: Gilead Sciences | N=52 ➔ 3 | Trial completion date: Jun 2027 ➔ Feb 2024 | Recruiting ➔ Terminated | Trial primary completion date: Jun 2027 ➔ Feb 2024; Study was terminated by Sponsor and the decision was not due to any safety or efficacy reasons.

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Infectious Disease • Novel Coronavirus Disease • Pediatrics

Oral administration of obeldesivir protects nonhuman primates against Sudan ebolavirus. (PubMed, Science) - "Obeldesivir (ODV, GS-5245) is an orally administered prodrug of the parent nucleoside of remdesivir (RDV) and is presently in phase 3 trials for COVID-19 treatment. In this work, we show that ODV and its circulating parent nucleoside metabolite, GS-441524, have similar in vitro antiviral activity against filoviruses, including Marburg virus, Ebola virus, and Sudan virus (SUDV)...Transcriptomics data show that ODV treatment delayed the onset of inflammation and correlated with antigen presentation and lymphocyte activation. Our results offer promise for the further development of ODV to control outbreaks of filovirus disease more rapidly."

Journal • Ebola Virus Disease • Infectious Disease • Inflammation • Novel Coronavirus Disease

OAKTREE: Study of Obeldesivir in Nonhospitalized Participants With COVID-19 (clinicaltrials.gov) - P3 | N=2011 | Completed | Sponsor: Gilead Sciences | Active, not recruiting ➔ Completed

Trial completion • Infectious Disease • Novel Coronavirus Disease

OAKTREE: Study of Obeldesivir in Nonhospitalized Participants With COVID-19 (clinicaltrials.gov) - P3 | N=2011 | Active, not recruiting | Sponsor: Gilead Sciences | Trial completion date: Aug 2024 ➔ Jan 2024 | Trial primary completion date: Jun 2024 ➔ Nov 2023

Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease

OAKTREE: Study of Obeldesivir in Nonhospitalized Participants With COVID-19 (clinicaltrials.gov) - P3 | N=2011 | Active, not recruiting | Sponsor: Gilead Sciences

Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease

Study of Obeldesivir in Children and Adolescents With COVID-19 (clinicaltrials.gov) - P2/3 | N=52 | Recruiting | Sponsor: Gilead Sciences

Trial completion date • Trial initiation date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease • Pediatrics

BIRCH: Study of Obeldesivir in Participants With COVID-19 Who Have a High Risk of Developing Serious or Severe Illness (clinicaltrials.gov) - P3 | N=468 | Terminated | Sponsor: Gilead Sciences | Active, not recruiting ➔ Terminated; The study was stopped early as it was determined there would not be a statistically significant treatment effect associated with the primary endpoint due to the low number of events.

Trial termination • Infectious Disease • Novel Coronavirus Disease

OAKTREE: Study of Obeldesivir in Nonhospitalized Participants With COVID-19 (clinicaltrials.gov) - P3 | N=2011 | Active, not recruiting | Sponsor: Gilead Sciences | Recruiting ➔ Active, not recruiting

Enrollment closed • Infectious Disease • Novel Coronavirus Disease

BIRCH: Study of Obeldesivir in Participants With COVID-19 Who Have a High Risk of Developing Serious or Severe Illness (clinicaltrials.gov) - P3 | N=469 | Active, not recruiting | Sponsor: Gilead Sciences | Recruiting ➔ Active, not recruiting | N=2300 ➔ 469

Enrollment change • Enrollment closed • Infectious Disease • Novel Coronavirus Disease

Exploring potential indications for remdesivir beyond COVID-19 (ASTMH 2023) - "GS-5245, another oral prodrug of GS-441524, has completed Phase I pharmacokinetic and safety evaluations and is currently in Phase III clinical trials for the treatment of high-risk COVID-19 patients. Collectively, these data support continued exploration of the antiviral prophylactic and therapeutic indications of RDV and oral nucleoside analogs. Proactive characterization of preclinical efficacy across other priority pathogens can enable rapid deployment of an effective treatment in response to emerging viral threats."

Ebola Virus Disease • Infectious Disease • Novel Coronavirus Disease • Respiratory Syncytial Virus Infections

Study of Obeldesivir in Children and Adolescents With COVID-19 (clinicaltrials.gov) - P2/3 | N=52 | Recruiting | Sponsor: Gilead Sciences | Not yet recruiting ➔ Recruiting

Enrollment open • Infectious Disease • Novel Coronavirus Disease • Pediatrics

Discovery of GS-5245 (Obeldesivir), an Oral Prodrug of Nucleoside GS-441524 That Exhibits Antiviral Efficacy in SARS-CoV-2-Infected African Green Monkeys. (PubMed, J Med Chem) - "Exposure-based SARS-CoV-2 efficacy relationships resulted in an estimated clinical dose of 350-400 mg twice daily. Importantly, all SARS-CoV-2 variants remain susceptible to 2, which supports development of 3 as a promising COVID-19 treatment."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Study of Obeldesivir in Children and Adolescents With COVID-19 (clinicaltrials.gov) - P2/3 | N=52 | Not yet recruiting | Sponsor: Gilead Sciences

New P2/3 trial • Infectious Disease • Novel Coronavirus Disease • Pediatrics

"Is there any publicly-available info regarding @GileadSciences' timeline for seeking regulatory approval of #GS5245/obeldesivir?" (@ClusteredErrors)

"New preprint by @GileadSciences & academic partners describes efficacy of #obeldesivir (GS-5245, aka oral version of GS-441524) in murine models: -SARS2 -MERS -SARS2-related bat CoV (RsSHC014) Key findings 🧵👇 1/6 https://t.co/uyHgXnYZj1" (@victoriacyanide)

Preclinical • Preprint

"Non-nucleoside? GS-441524 isobutyric ester (GS-5245) is a pro-drug of GS-441524 - a nucleoside analogue." (@Muller_Lab)

"We validated our findings in virtually all mouse models of #CoV pathogenesis available in the @Baric_Lab and @timothysheahan labs. We found that #GS5245 had strong therapeutic efficacy against bat CoV RsSHC014, #SARS2 Omicron, and protected mice against lethal SARSCoV disease." (@David_RMartinez)

Preclinical

Pharmacokinetics, safety and tolerability of GS-5245 in healthy participants (ECCMID 2023) - No abstract available

Clinical • PK/PD data

Study Evaluating GS-5245 in Nonhospitalized Participants With COVID-19 (clinicaltrials.gov) - P3 | N=1900 | Recruiting | Sponsor: Gilead Sciences | Not yet recruiting ➔ Recruiting

Enrollment open • Infectious Disease • Novel Coronavirus Disease

Study Evaluating GS-5245 in Nonhospitalized Participants With COVID-19 (clinicaltrials.gov) - P3 | N=1900 | Not yet recruiting | Sponsor: Gilead Sciences

New P3 trial • Infectious Disease • Novel Coronavirus Disease