adafosbuvir (AL-335) / J&J, Medivir - LARVOL DELTA

4'-Modified Nucleosides for Antiviral Drug Discovery: Achievements and Perspectives. (PubMed, Acc Chem Res) - P=N/A, P3 | "Currently, seven 4'-modified nucleoside drug candidates such as azvudine (also known as FNC), islatravir, censavudine, balapiravir, lumicitabine, AL-335, and 4-azidothymidine have progressed into clinical stages for treating viral infections. FNC cured the COVID-19 disease in almost all patients and showed better therapeutic efficacy than remdesivir. In this Account, we provide an overview of 4'-modified nucleoside analogs in clinical stages for antiviral therapies, highlighting the drug discovery strategies, structure-activity relationship studies, and preclinical/clinical studies and also give our perspectives on nucleoside-based antiviral drug discovery."

Journal • Human Immunodeficiency Virus • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • CD4

Identification and analysis of sugar transporters capable of co-transporting glucose and xylose simultaneously. (PubMed, Biotechnol J) - "Modelling studies of LST1_205437 revealed that Ala335 residue at sugar binding site can accommodates both glucose and xylose...In addition, we altered sugar preference of LST1_205437 by single amino acid mutation at Asn365. Our findings provide a new mechanistic insight on glucose and xylose transport mechanism of sugar transporters and the identified sugar transporters can be employed to develop engineered yeast strains for producing cellulosic biofuels and chemicals."

Journal

Synthesis and Anti-HCV Activities of 4'-Fluoro-2'-Substituted Uridine Triphosphates and Nucleotide Prodrugs: Discovery of 4'-Fluoro-2'-C-Methyluridine 5'-Phosphoramidate Prodrug (AL-335) for the Treatment of Hepatitis C Infection. (PubMed, J Med Chem) - "A lead compound (53) demonstrated high levels of the NTP in vitro in primary human hepatocytes and Huh-7 cells as well as in dog liver following a single oral dose. Compound 53 (AL-335) was selected for clinical development where it showed promising results in Phase 1 and II trials."

Journal • Hepatitis C Virus • Infectious Disease

JNJ-4178 (AL-335, Odalasvir, and Simeprevir) for 6 or 8 Weeks in Hepatitis C Virus-infected Patients without Cirrhosis: OMEGA-1. (PubMed, Hepatology) - P2b | "This multicenter, randomized, open-label study (NCT02765490) enrolled treatment-naïve and interferon (±ribavirin) treatment-experienced patients with HCV GT1, 2, 4, 5, or 6 infection. All randomized patients completed treatment. In HCV-infected patients, 6 and 8 weeks of treatment with JNJ-4178 resulted in SVR12 rates of 98.9% and 97.8%, respectively, and was well tolerated."

Clinical • Journal • Fibrosis • Hepatitis C Virus • Hepatology • Immunology • Infectious Disease • Liver Cirrhosis

A Study to Evaluate the Safety, Pharmacokinetics and Efficacy of the Combination of AL-335, ACH-3102, and Simeprevir (clinicaltrials.gov) - P2a; N=320; Recruiting; Sponsor: Alios Biopharma Inc.; Phase classification: P2 ➔ P2a; N=140 ➔ 320; Trial primary completion date: Jun 2016 ➔ Jul 2017

Enrollment change • Phase classification • Trial primary completion date • Biosimilar • Fibrosis • Hepatitis C Virus • Immunology

Short Duration AL-335, Odalasvir, With/Without Simeprevir, in Patients With HCV GT1 or 3 Infection Without Cirrhosis. (PubMed, Hepatology) - "In treatment-naïve subjects without cirrhosis, AL-335 + odalasvir + simeprevir for 6-8 weeks was generally safe and highly efficacious against HCV GT1. However, inadequate efficacy was observed for the 2-DAA regimen in GT1-infected subjects and the 3-DAA regimen in GT3-infected subjects."

Clinical • Journal • Biosimilar • Fibrosis • Hepatitis C Virus • Immunology • Infectious Disease

Efficacy and Safety of Combinations of AL-335, Odalasvir (ODV) and Simeprevir (SMV) or AL-335 and ODV in the Treatment of Chronic Hepatitis C Infection (clinicaltrials.gov) - P2; N=400; Not yet recruiting; Sponsor: Janssen Research & Development, LLC

New P2 trial • Biosimilar • Fibrosis • Hepatitis C Virus • Immunology

A Study to Evaluate the Effect of ACH-3102 and Simeprevir on AL-335 Pharmacokinetics in Healthy Volunteers (clinicaltrials.gov) - P1; N=32; Completed; Sponsor: Alios Biopharma Inc.; Recruiting ➔ Completed

Trial completion • Biosimilar • Hepatitis C Virus • Immunology • Inflammation

Evaluation of the efficacy and tolerability of JNJ-4178 (AL-335, odalasvir, and simeprevir) in hepatitis C virus-infected patients without cirrhosis: The Phase IIb OMEGA-1 study (AASLD 2017) - P2a,P2b; "The OMEGA-1 study will provide further understanding of the efficacy and tolerability of AL-335, ODV, and SMV (as JNJ-4178) in HCV GT1, 2, 4, 5, and 6 infected-pts without cirrhosis. Treatment was well tolerated and not associated with premature discontinuation. SVR12 results will be presented at the meeting."

Clinical • P2 data • Biosimilar • Fibrosis • Hepatitis C Virus • Immunology • Infectious Disease

A Study to Evaluate the Safety, Pharmacokinetics and Efficacy of the Combination of AL-335, ACH-3102, and Simeprevir (clinicaltrials.gov) - P2; N=140; Recruiting; Sponsor: Alios Biopharma Inc.; N=60 ➔ 140

Enrollment change • Biosimilar • Hepatitis C Virus • Immunology

JNJ: Pipeline Update (Johnson and Johnson Ltd) - Anticipated NME submission in US of 3DAA (ACH-3102, AL-335 and simeprevir combination) for hepatitis C infection in 2016-2019; Anticipated regulatory submission in EU of 3DAA (ACH-3102, AL-335 and simeprevir combination) for hepatitis C infection in 2016-2019

Anticipated EU regulatory • Anticipated NDA • Hepatitis C Virus

Achillion announces 100% SVR12 in the 6-week and 8-week cohorts in Janssen's phase 2 trial evaluating the triple combination treatment regimen including odalasvir, AL-335, and simeprevir for genotype 1 treatment-naïve HCV (Achillion Press Release) - P2, N=80; NCT02569710; Sponsor: Alios Biopharma Inc; "Achillion...announced that updated interim results were presented today in an ePoster describing a phase 2 study being conducted by Alios BioPharma...at the European Association for the Study of the Liver (EASL) Special Conference...reports that 100 percent of patients receiving treatment for as short as six weeks...achieved a sustained viral response 12 weeks after the completion of treatment (SVR12)."

Conference • P2 data • Hepatitis C Virus

Achillion: Q3 FY2016 Results (Achillion) - Anticipated initiation of enrollment in P2b OMEGA-1 trial (NCT02765490) of AL-335 in combination with odalasvir and simeprevir in HCV patients in Q4 2016

Anticipated enrollment status • Hepatitis C Virus

Medivir: Interim Report 2016 (Medivir) - Anticipated presentation of interim data from P2a trial (NCT02569710) of simeprevir in combination with odalasvir and AL-335 for hepatitis C infection at EASL-AASLD (Sep 23-24, 2016); Anticipated completion of P2 trial  of simeprevir in combination with odalasvir and AL-335 for hepatitis C infection by end 2016

Anticipated P2a data • Anticipated trial completion date • Hepatitis C Virus

Achillion announces 100% SVR reported in Janssen's phase 2a trial evaluating triple combination of odalasvir, AL-335, and simeprevir for genotype 1 treatment-naive HCV (Achillion Press Release) - P2a, N=80; NCT02765490; Sponsor: Janssen Research & Development, LLC; "Achillion...announced today that new interim results from a phase 2a study being conducted by Alios BioPharma...were published as part of the abstracts released for the upcoming European Association for the Study of the Liver (EASL) Special Conference...Of the 20 patients treated in cohort 1...100 percent remained HCV RNA undetectable 24 weeks after completing therapy (SVR24)...In cohort 1, there was a single serious adverse event (Mobitz Type 1 2nd degree atrioventricular block), which was attributed to treatment."

Anticipated conference • Conference • P2a data • Hepatitis C Virus

Achillion: Leerink Partners Rare Diseases & IO Roundtable Series (Leerink 2016, Achillion) - "Phase 2a Safety, PK and Efficacy Trial: Interim Results"

P2a data • Hepatitis C Virus

Achillion: Leerink Partners Rare Diseases & IO Roundtable Series (Leerink 2016, Achillion) - "Phase 2a Safety, PK and Efficacy Trial: Interim Results"

P2a data • Hepatitis C Virus

Medivir announces that Janssen decided to start a phase IIb study of combinations of simeprevir, odalasvir and al-335 for the treatment of hepatitis C (Businesswire) - P2, N=400; NCT02765490; Sponsor: Janssen Research & Development, LLC; "Medivir AB...today announces that Janssen Research & Development, LLC...has decided to initiate a phase IIb study to investigate the efficacy, safety and pharmacokinetics of different treatment regimens of AL-335, odalasvir, and simeprevir in treatment-naïve and treatment-experienced patients with chronic Hepatitis C Virus (HCV) genotype 1-6 infection, with and without cirrhosis...The study is intended to start in June 2016 and the estimated date for completion is July 2017."

Announcement • Anticipated trial completion date • Anticipated trial initiation date • Hepatitis C Virus

Achillion: William Blair & Company 2016 Growth Stock Conference (Achillion) - Anticipated initiation of P2b trial evaluating doublet and triplet regimens of odalasvir with AL-335 and/ simeprevir in hepatitis C infection with or without cirrhosis in Q3 2016

Anticipated trial initiation date • Hepatitis C Virus

AL-335 + odalasvir + simeprevir: Anticipated regulatory submission for hepatitis C infection in 2019 (Medivir) - Capital Markets Meeting

Anticipated regulatory • Hepatitis C Virus

A Study to Investigate the Safety, Pharmacokinetics, and Efficacy of Combination Treatment of AL-335, Odalasvir, and Simeprevir in Japanese Participants With Chronic Hepatitis C Genotype 1 or 2 Virus Infection, With or Without Compensated Cirrhosis Who Are Direct Acting Antiviral Treatment-naive (clinicaltrials.gov) - P2a; N=40; Not yet recruiting; Sponsor: Janssen Pharmaceutical K.K.

New P2a trial • Biosimilar • Fibrosis • Hepatitis C Virus • Immunology

Efficacy and Safety of Combinations of AL-335, Odalasvir (ODV) and Simeprevir (SMV) in the Treatment of Chronic Hepatitis C Infection (clinicaltrials.gov) - P2b; N=300; Recruiting; Sponsor: Janssen Research & Development, LLC; Not yet recruiting ➔ Recruiting

Enrollment open • Biosimilar • Fibrosis • Hepatitis C Virus • Immunology

JNJ-4178 (adafosbuvir, odalasvir, and simeprevir) in Japanese patients with chronic hepatitis C virus genotype 1 or 2 infection with or without compensated cirrhosis: the Phase IIa OMEGA-3 study. (PubMed, J Gastroenterol) - P2a; "In HCV GT1- and GT2-infected Japanese patients, treatment with JNJ-4178 was well tolerated and resulted in 100% of patients achieving SVR12."

Clinical • Journal • P2a data

Population Pharmacokinetics of AL-335 and Its Two Main Metabolites (ALS-022399, ALS-022227) in Monotherapy and in Combination with Odalasvir and/or Simeprevir. (PubMed, AAPS J) - "Internal evaluation confirmed that the population pharmacokinetic model developed was deemed appropriate to describe the time course of AL-335, ALS-022399, and ALS-022227 plasma concentrations and their associated variability in both healthy and HCV-infected subjects, as well as the interaction effect of simeprevir and/or odalasvir over AL-335 and its metabolites in healthy subjects. This model can be used as a starting point to evaluate drug-drug interaction processes in HCV-infected patients and support the development of a direct-acting antiviral (DAA) combination."

Clinical • Combination therapy • Journal • Monotherapy • PK/PD data