ombitasvir (ABT-267) / AbbVie - LARVOL DELTA

Investigating the effect of permeation enhancers on oral absorption of a BCS IV compound, ombitasvir, utilizing animal models. (PubMed, J Pharm Sci) - "It was concluded that the dissolution rate of the form/formulation, the amount of drug concomitantly available with PE at the site of absorption, the association of PE with the precipitated amorphous phase and the particle size of this phase impacts the overall performance of PE towards improving oral bioavailability. The results of this study present promising approaches to formulate BCS IV compounds."

Journal • Preclinical

Prevalence of resistance-associated substitutions (RAS) in hepatitis C virus in the Former Soviet Union countries. (PubMed, BMJ Open Gastroenterol) - "The high prevalence of HCV genotypes 1b and 3a in the FSU region and the presence of specific RASs should be considered when determining the most effective treatment regimen for HCV-infected individuals in the FSU countries."

Journal • Hepatitis C • Hepatology • Infectious Disease • Inflammation

Pyrrolidine SS13 Induces Oxidative Stress and Autophagy-Mediated Cell Death in Colorectal Cancer Cells. (PubMed, Eur J Pharm Sci) - "Moreover, many medicinal drugs contain pyrrolidine moiety such as sunitinib (anticancer drug), telaprevir and ombitasvir (antiviral drugs) or ramipril (antihypertensive drug)...Finally, chloroquine, an inhibitor of autophagy, enhanced cell survival and suppressed the cytotoxic effect of SS13 in HCT116 and Caco-2 cells, indicating that SS13 contributes to autophagy-mediated cell death. Taken together, our results suggest that oxidative stress and autophagy participate in the antiproliferative effect of pyrrolidine SS13 on colorectal cancer cells. Further research using primary cell cultures obtained from different animal tissues as well as performing in vivo experiments is needed to understand these processes in detail and to investigate the potential therapeutic application of new pyrrolidine derivatives."

Journal • Colorectal Cancer • Oncology • Solid Tumor • ATG7 • SOD2

A combination of nirmatrelvir and ombitasvir boosts inhibition of SARS-CoV-2 replication. (PubMed, Antiviral Res) - "The increased potency of the nirmatrelvir-ombitasvir combination, over nirmatrelvir alone afforded a greater than 3 log10 reduction in viral titre, which is sufficient to fully prevent the detection of progeny SARS-CoV-2 viral particles at 48 h post infection. The mechanism of this potentiated effect was shown to be, in-part, due to joint inhibition of the 3-chymotrypsin-like protease via a positive allosteric modulation mechanism."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Identification of novel compounds and repurposing of FDA drugs for 1-deoxy-D-xylulose 5-phosphate reductoisomerase enzyme of Plasmodium falciparum to combat malaria resistance. (PubMed, Int J Biol Macromol) - "Following our computational pipeline, we found five novel ZINC20 compounds (Z-2, Z-3, Z-10, Z-13, and Z-14) and three FDA drugs (Aliskiren, Ceftolozane, and Ombitasvir) that showed striking docking energy (ranging from -8.405 to -10.834 kcal/mol), and strong interactions with key binding site residues (Ser-269, Ser-270, Ser-306, Asn-311, Lys-312, and Met-360) of PfIspC. Notably, the binding free energy estimation confirmed high binding affinity (varied from -11.68 to -33.16 kcal/mol) of these compounds for PfIspC. Our findings could contribute to the ongoing efforts in combating malaria and invite experimental-lab researchers for validation."

Journal • Infectious Disease • Malaria

TOTAL HCV PATIENTS TREATED WITH DIRECT ACTING ANTIVIRALS SINCE 2014 (AASLD 2023) - "National registration dates of sofosbuvir (SOF), ombitasvir + paritaprevir + ritonavir, glecaprevir + pibrentasvir, and elbasvir + grazoprevir based treatments were used to allocate treated patients to specific regimens. The access to DAAs in low- and middle-income countries (LMIC) has had a profound impact on the total number of HCV patients treated globally with generic sofosbuvir + daclatasvir being the preferred treatment. With 89% of all HCV infections in LMIC, immediate access to generic versions of the latest drugs is needed to achieve the global elimination targets. The high-income countries have been very proactive in treating their HCV infected populations and removing all restrictions."

Clinical • Hepatitis C • Hepatology • Infectious Disease • Inflammation

The efficacy and safety of direct-acting antiviral regimens for end-stage renal disease patients with HCV infection: a systematic review and network meta-analysis. (PubMed, Front Public Health) - "Network meta-analyses of the DAAs found that receiving ombitasvir (OBV)/paritaprevir (PTV)/ritonavir (R) plus dasabuvir (DSV), glecaprevir (G)/pibrentasvir (P), and sofosbuvir (SOF)/ledipasvir (LDV) ranked as the top three efficacy factors for the HCV-infected ESRD patients...DAA regimens without Ribavirin or SOF showed the lowest rates of AEs (49.9%; 95% CI, 38.4%-61.5%) in HCV-infected ESRD patients...The OBV/PTV/R plus DSV, SOF/Velpatasvir (VEL), SOF/Ledipasvir (LDV), and SOF/DCV would be reliable alternatives for HCV treatment with comparable efficacy and safety profiles. https://www.crd.york.ac.uk/prospero/#searchadvanced, PROSPERO: CRD42021242359."

Retrospective data • Review • Chronic Kidney Disease • Fibrosis • Hepatitis C • Hepatology • Immunology • Infectious Disease • Inflammation • Nephrology • Renal Disease

Implications of 3D conformations on protein binding and crystal polymorphism of NS5A inhibitors ombitasvir and pibrentasvir (ACS-Fall 2023) - "In contrast for pibrentasvir, the cis/cis conformers were the most abundant, low-energy minima conformers. The degree of conformational flexibility and/or the ability to adopt different conformations translate into drug development implications, ranging from difficulty of crystallizability to intricate crystal form landscape, such that ombitasvir and pibrentasvir embody some of the key challenges in contemporary solid-state chemistry."

Hepatitis C • Hepatology • Infectious Disease • Inflammation

In silico Antivirus Repurposing and its Modification to Organoselenium Compounds as SARS-CoV-2 Spike Inhibitors. (PubMed, Pak J Biol Sci) - "The best-modified ligand was chosen by analyzing the ADME-Tox property, RMSD value and binding energy value. <b></b> The best three unmodified ligands, Ombitasvir, Elbasvir and Ledipasvir, have a binding energy value of -15.8065, -15.3842 and -15.1255 kcal mol¹, respectively and the best three modified ligands ModL1, ModL2 and ModL3 has a binding value of -15.6716, -13.9489 and -13.2951 kcal mol¹, respectively with an RMSD value of 1.7109 Å, 2.3179 Å and 1.7836 Å."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

The effect of different direct antivirals on hepatic steatosis in nondiabetic and naïve hepatitis C-infected Egyptian patients. (PubMed, Egypt J Intern Med) - "The patients were divided into four groups according to their treatment regimens as follows: group A: 25 patients who received sofosbuvir (400 mg) and daclatasvir (60 mg) daily for 12 weeks; group B: 25 patients who received sofosbuvir (400 mg) and ledipasvir (90 mg) daily for 12 weeks; group C: 25 patients who received ombitasvir (12.5 mg), paritaprevir (75 mg), and ritonavir (50 mg) daily for 12 weeks; and group D: 25 patients who received sofosbuvir (400 mg) and simeprevir (150 mg) daily for 12 weeks. There is a noticed improvement in the FibroScan, NAFLD score, and lipid profile after achieving the SVR-12 weeks. However, LDL is increased after viral cure, mostly due to viral-host molecular interaction."

Journal • Fibrosis • Gastroenterology • Hepatitis C • Hepatology • Immunology • Infectious Disease • Inflammation • Non-alcoholic Fatty Liver Disease

The effectiveness and safety of direct-acting antivirals for hepatitis C virus treatment: A single-center experience in Saudi Arabia. (PubMed, Saudi Pharm J) - "All patients with HCV treated with either ledipasvir plus sofosbuvir (LDS/SOF) ± ribavarin (RBV) or ombitasvir-paritaprevir-ritonavir (OBV/PTV/r) ± dasabuvir (DSV) ± RBV were included...Medications were well tolerated with minimal side effects, including vomiting, nausea, and weakness. DAAs regimens are associated with high rates of SVR12 and are well tolerated with a good safety profile in Saudi HCV-infected patients."

Journal • Hepatitis C • Hepatology • Infectious Disease • Inflammation

Effects of Achieving Sustained Virologic Response after Direct-Acting Antiviral Agents on Long-Term Liver Fibrosis in Diabetics vs. in Non-Diabetic Patients with Chronic Hepatitis C Infection. (PubMed, Biomedicines) - "Two pills/day of Ombitasvir 12.5 mg/Paritaprevir 75 mg/Ritonavir 50 mg and two pills/day of Dasabuvir 250 mg were given to the patients for 8 weeks. Our study found that successfully treating HCV infection can play a significant role in reducing fibrosis in T2DM patients. In comparison to those of ActiTest and SteatoTest, FibroMax scores showed a significantly greater reduction in T2DM patients than in treatment-naive patients."

Journal • Diabetes • Fibrosis • Hepatitis C • Hepatology • Immunology • Infectious Disease • Inflammation • Liver Cirrhosis • Metabolic Disorders • Solid Tumor • Type 2 Diabetes Mellitus

Discovery of HCV NS5A inhibitors ombitasvir (ABT-267) and pibrentasvir (ABT-530) and bromodomain and extra-terminal domain (BET) inhibitors mivebresib (ABBV-075) and ABBV-744 (ACS-Fall 2022) - "Our initial medicinal chemistry exploration of HCV NS5A resulted in the discovery of ombitasvir (ABT-267), the HCV NS5A inhibitor that is a key component of Viekira Pak, AbbVie’s 1st generation treatment for HCV. Further research culminated in the discovery of pibrentasvir (ABT-530), the HCV NS5A inhibitor that is a key component of Mavyret, AbbVie’s 2nd generation treatment for HCV...Structure-based drug design at AbbVie led to the discovery of a novel and potent pan BET inhibitor, mivebresib (ABBV-075, phase 1). Additional effort led to the discovery of the BD2 selective BET inhibitor ABBV-744 (phase 1)."

Hepatitis C • Hepatology • Infectious Disease • Inflammation • Oncology

Liver Stiffness Is Markedly Decreased After Chronic Hepatitis C Treatment. (PubMed, Ultrasound Q) - "The LS value determined by the elastography point quantification technique is more effective than other noninvasive laboratory methods in demonstrating the CHC treatment response in clinical practice."

Journal • Fibrosis • Hepatitis C • Hepatology • Immunology • Infectious Disease • Inflammation • Liver Cirrhosis

Assessing the Risk of Decrease in Kidney Function in Patients Prescribed Direct-Acting Antivirals for Hepatitis C Utilizing the MID-NET Medical Information Database Network in Japan. (PubMed, Ther Innov Regul Sci) - "Among the 10 patterns, a significant increase in the incidence rate ratio (P < 0.01) was observed in the prescription patterns of concomitant use of telaprevir with peginterferon alpha and ribavirin, concomitant use of daclatasvir hydrochloride with asunaprevir, and ombitasvir hydrate combined with paritaprevir hydrate and ritonavir, which were concomitantly used with ribavirin; such an increase was not observed in the other prescription patterns. The effects of DAAs on kidney function may differ among drugs, suggesting the possibility that the risk of kidney disease is not a class effect of DAAs and should be evaluated individually for each DAA."

Journal • Hepatitis C • Hepatology • Infectious Disease • Inflammation • Nephrology • Renal Disease

Combination of antiviral drugs inhibits SARS-CoV-2 polymerase and exonuclease and demonstrates COVID-19 therapeutic potential in viral cell culture. (PubMed, Commun Biol) - "Here we report the identification of hepatitis C virus NS5A inhibitors Pibrentasvir and Ombitasvir as SARS-CoV-2 exonuclease inhibitors. In the presence of Pibrentasvir, RNAs terminated with the active forms of the prodrugs Sofosbuvir, Remdesivir, Favipiravir, Molnupiravir and AT-527 were largely protected from excision by the exonuclease, while in the absence of Pibrentasvir, there was rapid excision. Due to its unique structure, Tenofovir-terminated RNA was highly resistant to exonuclease excision even in the absence of Pibrentasvir. Viral cell culture studies also demonstrate significant synergy using this combination strategy. This study supports the use of combination drugs that inhibit both the SARS-CoV-2 polymerase and exonuclease for effective COVID-19 treatment."

Journal • Preclinical • Hepatitis C • Hepatology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases

Deep Learning Driven Drug Discovery: Tackling Severe Acute Respiratory Syndrome Coronavirus 2. (PubMed, Front Microbiol) - "Consequently, deep learning has been successfully used for the identification of a number of potential drugs against SARS-CoV-2, including Atazanavir, Remdesivir, Kaletra, Enalaprilat, Venetoclax, Posaconazole, Daclatasvir, Ombitasvir, Toremifene, Niclosamide, Dexamethasone, Indomethacin, Pralatrexate, Azithromycin, Palmatine, and Sauchinone. This mini-review discusses recent advances and future perspectives of deep learning-based SARS-CoV-2 drug discovery."

Journal • Review • Cognitive Disorders • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

[VIRTUAL] CHANGES IN IMMUNE CELL PROFILES BEFORE AND AFTER TREATMENT WITH DIRECT-ACTING ANTIVIRAL AGENTS IN PATIENTS WITH CHRONIC HEPATITIS C (AASLD 2021) - " Forty-seven and 30 received patients treated by asunaprevir/daclatasvir and ombitasvir / paritaprevir / ritonavir (OBV/PTV/r), respectively, were analyzed in this study. Our study showed that DAAs treatment changes host immune cell profiles and can decrease the frequency of T cells with high expression of PD-1 by eliminating F protein . These results suggest that the strength of immune response against virus or tumor changes after DAAs treatment ."

Clinical • IO biomarker • Hepatitis C • Hepatology • Immune Modulation • Infectious Disease • Inflammation • Oncology • CD8 • CTLA4 • CXCR3 • FOXP3 • IL2RA • PD-1

A Follow up Study Designed to Obtain Long Term Data on Subjects Who Either Achieved a Sustained Virologic Response or or Did Not Achieve a Sustained Virologic Response in an Abbott Sponsored Hepatitis C Study (clinicaltrials.gov) - P3; N=500; Active, not recruiting; Sponsor: AbbVie (prior sponsor, Abbott); Enrolling by invitation -> Active, not recruiting

Enrollment closed • Biosimilar • Hepatitis C Virus • Immunology • Inflammation

TOPAZ-I: A Study to Evaluate Long-term Outcomes Following Treatment With ABT-450/Ritonavir/ABT-267 (ABT-450/r/ABT-267) and ABT-333 With or Without Ribavirin (RBV) in Adults With Genotype 1 Chronic Hepatitis C Virus (HCV) Infection (clinicaltrials.gov) - P3; N=1650; Active, not recruiting; Sponsor: AbbVie; Trial primary completion date: Sep 2016 ➔ Jan 2017

Trial primary completion date • Biosimilar • Hepatitis C Virus • Hepatocellular Cancer • Immunology • Oncology

Potential for Drug-Drug Interactions between Antiretrovirals and HCV Direct Acting Antivirals in a Large Cohort of HIV/HCV Coinfected Patients. (PubMed) - "Significant potential drug-drug interactions are expected between cART and the currently available DAAs in the majority of HIV/HCV coinfected patients. Sofosbuvir/ledipasvir and sofosbuvir/daclatasvir with or without ribavirin appeared the most suitable combinations in our population. A close collaboration between hepatologists and HIV/AIDS specialists appears necessary for the management of HCV treatment concomitantly to cART."

Journal • Biosimilar • Hepatitis C Virus • Immunology • Inflammation

Effectiveness of Paritaprevir/Ritonavir - Ombitasvir, +/- Dasabuvir, +/- Ribavirin in Patients With Chronic Hepatitis C - An Observational Study in Belgium (clinicaltrials.gov) - P=N/A; N=440; Recruiting; Sponsor: AbbVie

New trial • Biosimilar • Hepatitis C Virus • Immunology • Inflammation

A Study to Evaluate Chronic Hepatitis C Infection in Cirrhotic Adults With Genotype 1b Infection (clinicaltrials.gov) - P3; N=36; Active, not recruiting; Sponsor: AbbVie; Recruiting -> Active, not recruiting

Enrollment closed • Biosimilar • Fibrosis • Hepatitis C Virus • Immunology • Inflammation

Restrictions for reimbursement of direct-acting antiviral treatment for hepatitis C virus infection in Canada: a descriptive study. (PubMed) - CMAJ Open - "This review of criteria of reimbursement of HCV direct-acting antivirals in Canada showed substantial interjurisdictional heterogeneity. The findings could inform health policy and support the development and adoption of a national HCV strategy."

Journal • Biosimilar • Fibrosis • Gene Therapies • Hepatitis C Virus • Immunology

Gilead Sciences expecting blockbuster sales of hepatitis C drug Sovaldi (frenchtribune.com) - "Stock price of biotechnology major Gilead Sciences surged 36% this year, thanks to blockbuster sales of Sovaldi, the hepatitis C drug the company launched last December. However, Food and Drug Administration, FDA is set to make a decision on AbbVie's hepatitis C cocktail this month. If it's approved, Gilead Sciences shares may come under pressure as the company could lose its market dominance and also face pressure on margins...AbbVie will be only be able to displace Harvoni on the basis of price, rather than efficiency."

Anticipated regulatory • Stock price • Hepatitis C Virus