Elbasvir: A Comprehensive Pharmacological and Clinical Monograph

I. Executive Summary

Elbasvir (DrugBank ID: DB11574) is a highly potent, second-generation direct-acting antiviral (DAA) agent that has become a cornerstone in the curative treatment of chronic Hepatitis C virus (HCV) infection. It is not administered as a monotherapy but serves as a critical component of the oral, once-daily, fixed-dose combination product Zepatier®, where it is co-formulated with the HCV NS3/4A protease inhibitor grazoprevir.[1] Elbasvir functions as a selective inhibitor of the HCV Nonstructural Protein 5A (NS5A), a multifunctional phosphoprotein essential for both viral RNA replication and the assembly of new virions. By targeting this protein, elbasvir effectively halts the viral lifecycle at two critical junctures.[3]

Clinically, the elbasvir/grazoprevir combination is indicated for the treatment of chronic HCV genotypes 1 and 4 in adults and pediatric patients aged 12 years and older or weighing at least 30 kg.[5] The regimen has demonstrated exceptionally high rates of sustained virologic response (SVR)—defined as undetectable HCV RNA 12 weeks after completion of therapy and considered a virologic cure—with SVR rates consistently ranging from 94% to 100% in pivotal clinical trials.[1]

A defining feature of the elbasvir/grazoprevir regimen is its established efficacy and safety in difficult-to-treat patient populations. Its pharmacokinetic profile, characterized by minimal renal excretion, makes it a preferred therapeutic option for patients with severe chronic kidney disease (CKD), including those requiring hemodialysis—a population with historically limited treatment options.[7] Furthermore, extensive clinical data support its use in patients with compensated cirrhosis, prior treatment failure with interferon-based regimens, and those with HCV/HIV co-infection.[7]

Despite its high efficacy, the clinical application of elbasvir is subject to specific limitations. Its activity is primarily restricted to genotypes 1 and 4, making it less versatile than newer pangenotypic agents. A significant clinical consideration is the impact of baseline NS5A resistance-associated polymorphisms (RAPs) in patients with genotype 1a, which necessitates pre-treatment viral genetic testing to guide the therapeutic strategy, potentially extending treatment duration and requiring the addition of ribavirin.[5] From a safety perspective, all DAA regimens containing elbasvir carry an FDA black box warning regarding the risk of Hepatitis B Virus (HBV) reactivation in co-infected patients. The regimen is also contraindicated in patients with moderate-to-severe hepatic impairment (Child-Pugh B or C) due to risks associated with the grazoprevir component.[6]

II. Chemical Identity and Physicochemical Properties

Elbasvir is a complex organic heterotetracyclic small molecule that has been systematically characterized to ensure precise identification for research, clinical, and regulatory purposes.[3] Developed by Merck, it was initially identified by the developmental code MK-8742.[1]

Systematic Identification and Structural Information

The definitive identity of elbasvir is established through a collection of unique identifiers and structural descriptors. Its formal IUPAC name is Dimethyl N,N'-(benzoxazine-3,10-diyl]bis{1H-imidazole-5,2-diyl-(2S)-pyrrolidine-2,1-diyl})biscarbamate.[2] For computational chemistry and database interoperability, its structure is represented by the InChIKey BVAZQCUMNICBAQ-PZHYSIFUSA-N.[2] The molecule's chemical formula is

C49​H55​N9​O7​, corresponding to an average molecular weight of 882.035 g·mol⁻¹ and a monoisotopic mass of 881.422445147 Da.[1]

Physicochemical Properties and Formulation Characteristics

Elbasvir typically presents as a white to off-white crystalline solid.[12] Its solubility profile is characteristic of a large, lipophilic molecule, showing good solubility in organic solvents such as dimethylformamide (DMF) at 25-33 mg/ml, dimethyl sulfoxide (DMSO) at 20 mg/ml, and ethanol at 25-33 mg/ml. Conversely, it has very poor aqueous solubility, as demonstrated by its low solubility in a phosphate-buffered saline (PBS) and ethanol mixture (0.33 mg/ml).[11] For long-term preservation, the compound should be stored in a dry, dark environment at -20°C, though it is stable enough for shipment at ambient temperatures.[10]

From a safety and handling perspective, powdered elbasvir is noted to have the potential to form an explosive dust-air mixture during processing or handling.[15] Furthermore, it is classified as very toxic to aquatic life with long-lasting effects (GHS hazard statement H410), requiring appropriate disposal procedures.[13]

Table 1: Key Identifiers and Physicochemical Properties of Elbasvir

Property/Identifier	Value	Reference(s)
DrugBank ID	DB11574	1
CAS Number	1370468-36-2	1
Synonyms / Codes	MK-8742, MK8742, MK 8742	1
Chemical Formula	C49​H55​N9​O7​	1
Average Molecular Weight	882.035 g·mol⁻¹	1
Monoisotopic Mass	881.422445147 Da	1
IUPAC Name	Dimethyl N,N'-(benzoxazine-3,10-diyl]bis{1H-imidazole-5,2-diyl-(2S)-pyrrolidine-2,1-diyl})biscarbamate	2
InChIKey	BVAZQCUMNICBAQ-PZHYSIFUSA-N	2
Appearance	White to off-white solid	12
Solubility (DMSO)	20 mg/ml	11
Solubility (Ethanol)	33 mg/ml	11
Storage	-20°C (long-term)	10

III. Comprehensive Pharmacological Profile

A. Pharmacodynamics: Mechanism of Antiviral Action

Elbasvir is classified as a direct-acting antiviral (DAA) that exerts its therapeutic effect through potent and selective inhibition of the Hepatitis C Virus (HCV) Nonstructural Protein 5A (NS5A).[1] NS5A is a large, zinc-binding phosphoprotein with a complex, multifunctional role in the viral lifecycle. It is an essential component of the HCV replication complex—a structure often referred to as the "membranous web"—where viral RNA synthesis occurs. Beyond its role in replication, NS5A is also critically involved in the downstream processes of virion assembly and release from the host cell.[3]

Elbasvir's mechanism of action involves direct binding to the NS5A protein, which leads to a profound disruption of these viral processes. While the exact molecular interactions are complex, the functional consequences include the potent and early blockade of the formation of new viral replicase complexes, effectively preventing the virus from creating the machinery needed to copy its own genome.[11] Additionally, elbasvir is thought to interfere with essential NS5A-mediated signaling pathways and alter the protein's normal subcellular distribution, further crippling the virus's ability to propagate.[1] This dual inhibition of both replication and assembly makes NS5A an exceptionally effective antiviral target.[4]

The potency of elbasvir is remarkable, with in vitro studies demonstrating activity at picomolar to low nanomolar concentrations against susceptible HCV genotypes. For instance, an EC50 value of 2.2 pM has been reported in cell culture systems expressing an HCV genotype 1a derivative, highlighting its profound intrinsic activity.[11] Elbasvir demonstrates potent inhibitory activity against a broad range of genotypes in laboratory settings, including 1a, 1b, 2a, 3a, 4a, 5a, and 6a.[11] However, its clinical development and regulatory approval have focused on its high efficacy against genotypes 1 and 4.[1]

The high potency of elbasvir also underlies its primary clinical challenge: viral resistance. The efficacy of the drug can be significantly compromised by the presence of specific pre-existing amino acid substitutions in the NS5A protein, known as resistance-associated polymorphisms (RAPs).[7] For patients with HCV genotype 1a, polymorphisms at positions 28, 30, 31, or 93 are of particular concern.[5] The presence of these RAPs at baseline can reduce the probability of achieving SVR with a standard 12-week course of therapy. This direct link between molecular virology and clinical outcome has led to a key recommendation in the drug's prescribing information: all patients with genotype 1a infection should undergo baseline testing for the presence of these NS5A RAPs. The results of this test directly inform the treatment strategy, with patients harboring these RAPs being recommended for a longer, 16-week regimen that includes the addition of ribavirin to overcome the reduced susceptibility.[5]

B. Pharmacokinetics: Absorption, Distribution, Metabolism, and Excretion (ADME)

The pharmacokinetic profile of elbasvir is well-characterized and supports a convenient once-daily oral dosing schedule. Its ADME properties are also fundamental to understanding its clinical utility in specific populations and its potential for drug-drug interactions.

Absorption: Following oral administration, elbasvir reaches peak plasma concentrations (Tmax​) within a window of 3 to 6 hours.[1] Its absolute bioavailability is estimated to be 32%, indicating that a significant portion of the oral dose does not reach systemic circulation.[1] While administration with a high-fat meal can increase the peak concentration (

Cmax​) by approximately 1.5-fold, this change is not considered clinically significant, allowing the fixed-dose combination tablet (Zepatier) to be taken with or without food.[1] With once-daily dosing, elbasvir achieves steady-state plasma concentrations in approximately 6 days.[2]

Distribution: Elbasvir is extensively bound to plasma proteins, with over 99.9% of the drug in circulation associated with human serum albumin and α1-acid glycoprotein.[1] This high degree of protein binding limits the amount of free, pharmacologically active drug. It has a large apparent volume of distribution (

Vd​) of 680 liters, which suggests that the drug distributes widely into tissues beyond the plasma compartment, including its primary site of action in the liver.[1]

Metabolism: Elbasvir is partially metabolized in the liver. The primary metabolic pathway is oxidative metabolism mediated by the cytochrome P450 3A (CYP3A4) enzyme system.[1] A key finding from human studies is the absence of any detectable circulating metabolites in plasma, which indicates that the parent drug is the sole active moiety responsible for the antiviral effect.[1] This reliance on CYP3A4 for metabolism is the direct cause of its extensive and clinically significant drug-drug interaction profile, making it susceptible to altered plasma levels when co-administered with potent inducers or inhibitors of this enzyme.

Excretion: The elimination of elbasvir occurs predominantly through the hepatobiliary system. Over 90% of an administered dose is excreted in the feces, likely as a combination of unchanged drug and metabolites. In contrast, renal excretion is a negligible pathway, with less than 1% of the drug eliminated in the urine.[1] This pharmacokinetic property is of paramount clinical importance, as it means that renal impairment, regardless of its severity, does not significantly impact the drug's clearance. This is the fundamental reason why elbasvir is a safe and effective treatment option for patients with severe CKD, including those on dialysis. The geometric mean apparent terminal half-life (

t1/2​) of elbasvir in HCV-infected patients is approximately 24 hours, which provides the rationale for its once-daily dosing regimen.[1]

Table 2: Summary of Elbasvir Pharmacokinetic Parameters

Parameter	Value	Reference(s)
Route of Administration	Oral	2
Absolute Bioavailability	32%	1
Time to Peak Plasma Conc. (Tmax​)	3–6 hours	1
Food Effect	Not clinically relevant	1
Time to Steady State	~6 days	2
Plasma Protein Binding	>99.9%	1
Apparent Volume of Distribution (Vd​)	680 L	1
Primary Metabolic Enzyme	CYP3A4	2
Primary Route of Excretion	Feces (>90%)	1
Renal Excretion	<1%	1
Apparent Terminal Half-Life (t1/2​)	~24 hours	1

IV. Clinical Efficacy in the Treatment of Hepatitis C

The clinical development of elbasvir was conducted exclusively as part of a fixed-dose combination with grazoprevir, marketed as Zepatier®. This strategic pairing was designed to deliver a highly effective, all-oral regimen with a high barrier to resistance.

A. Overview of the Zepatier® (Elbasvir/Grazoprevir) Combination

The rationale for combining elbasvir with grazoprevir is rooted in fundamental virology. By targeting two distinct and essential viral proteins—NS5A (elbasvir) and the NS3/4A protease (grazoprevir)—the regimen attacks the HCV lifecycle at multiple points simultaneously.[4] This synergistic approach dramatically reduces the probability of the virus developing resistance mutations that could lead to treatment failure, a common issue with early DAA monotherapies.[2] The Zepatier tablet contains a fixed dose of 50 mg of elbasvir and 100 mg of grazoprevir and is administered as a single tablet once daily.[6] The extensive clinical development program, encompassing numerous Phase II and III trials such as C-EDGE, C-WORTHY, C-SURFER, and C-SALVAGE, was designed to evaluate this combination across a broad and diverse spectrum of HCV-infected patients.[21]

B. Efficacy Across Patient Populations

The primary endpoint in all pivotal trials was SVR12, which serves as the benchmark for a virologic cure. Across these studies, the elbasvir/grazoprevir regimen demonstrated consistently high efficacy for its indicated genotypes. Pooled analyses show SVR rates of 94-97% for genotype 1 and 97-100% for genotype 4 following a 12-week treatment course.[1]

• Treatment-Naïve Patients: The C-EDGE Treatment-Naïve (TN) trial was a cornerstone study that established efficacy in patients without prior HCV treatment. In this trial, a 12-week course of Zepatier resulted in an overall SVR12 rate of 95%. When stratified by genotype, the SVR12 rates were 92% for genotype 1a, 99% for genotype 1b, and 100% for genotype 4.[7]
• Treatment-Experienced Patients: The C-EDGE Treatment-Experienced (TE) trial evaluated the regimen in patients who had previously failed therapy with peginterferon and ribavirin (PegIFN/RBV). In this more difficult-to-treat population, SVR4 rates were 95% for those receiving Zepatier for 12 weeks and 98% for those receiving Zepatier plus ribavirin for 16 weeks. The addition of ribavirin was particularly beneficial for treatment-experienced patients with genotype 4, increasing the SVR rate from 78% to 100%.[7] In the C-SALVAGE study, which enrolled patients who had failed a prior regimen containing a first-generation protease inhibitor, a 12-week course of Zepatier plus ribavirin achieved an impressive 96% SVR12 rate.[7]
• Patients with Compensated Cirrhosis: Across multiple trials, Zepatier proved highly effective in patients with compensated (Child-Pugh A) cirrhosis, a group historically associated with lower response rates to interferon-based therapies. SVR rates in cirrhotic patients were consistently high and comparable to those in non-cirrhotic patients, often exceeding 95%.[7]

C. Efficacy in Special and Difficult-to-Treat Populations

A key strength of the elbasvir/grazoprevir clinical program was its deliberate focus on patient populations with significant unmet medical needs. This strategic emphasis not only proved the regimen's versatility but also carved out a distinct clinical niche for Zepatier in a competitive market.

• Chronic Kidney Disease (CKD): The C-SURFER trial is a landmark study that definitively established the utility of Zepatier in patients with advanced CKD. The trial enrolled genotype 1 patients with stage 4 or 5 CKD, the majority of whom were on hemodialysis. The SVR12 rate was 94% in the primary intent-to-treat analysis and rose to 99% in a modified analysis that excluded non-virologic failures (e.g., death, loss to follow-up). This exceptional outcome, directly attributable to elbasvir's non-renal clearance pathway, positioned Zepatier as a premier treatment option for this vulnerable population.[7]
• HCV/HIV Co-infection: The C-EDGE Coinfection trial demonstrated that the efficacy of Zepatier is not diminished by concurrent HIV infection. In this study of 218 treatment-naïve, co-infected patients, a 12-week course of Zepatier achieved an overall SVR12 of 96.3%. This confirmed its utility in co-infected patients, provided their antiretroviral regimen does not include contraindicated drugs.[7]
• Patients on Opioid Agonist Therapy: The C-EDGE CO-STAR study addressed concerns about treating patients who inject drugs and are receiving opioid agonist therapy. Preliminary data showing a 96% SVR4 rate provided evidence that this population can be treated successfully, underscoring the regimen's effectiveness even in the context of potential adherence challenges.[7]

Table 3: Summary of Efficacy (SVR12 Rates) of Elbasvir/Grazoprevir from Key Phase III Clinical Trials

Trial Name	Patient Population	Regimen	Overall SVR12 Rate (%)	Key Subgroup SVR12 Rate (%)	Reference(s)
C-EDGE TN	Treatment-Naïve, GT1/4/6, +/- Cirrhosis	EBR/GZR for 12 weeks	95%	GT1a: 92%, GT1b: 99%, GT4: 100%	7
C-EDGE TE	PegIFN/RBV-Experienced, GT1/4, +/- Cirrhosis	EBR/GZR +/- RBV for 12/16 weeks	92-97%	GT4 + RBV: 100%	5
C-SALVAGE	PI-Experienced, GT1, +/- Cirrhosis	EBR/GZR + RBV for 12 weeks	96%	N/A	7
C-SURFER	GT1 with Stage 4/5 CKD (incl. dialysis)	EBR/GZR for 12 weeks	99% (modified analysis)	N/A	7
C-EDGE Coinfection	Treatment-Naïve, GT1/4/6 with HIV Co-infection	EBR/GZR for 12 weeks	96.3%	Cirrhotic: 100%	7

V. Safety, Tolerability, and Risk Management

The elbasvir/grazoprevir regimen is generally well-tolerated, with a safety profile that compares favorably to older interferon-based therapies and other DAA regimens. However, it is associated with specific risks and contraindications that require careful patient selection and monitoring.

A. Profile of Adverse Events

In placebo-controlled clinical trials, the most frequently reported adverse reactions with Zepatier were generally mild and included fatigue (11%), headache (10%), and nausea (5%).[1] When the regimen includes ribavirin, the adverse event profile is dominated by the known side effects of ribavirin. In these cases, the most common moderate or severe adverse reactions were anemia (8%) and headache (6%). A predictable decrease in hemoglobin levels (mean change of approximately -2.2 g/dL) was observed in patients receiving ribavirin, which typically resolved after treatment completion.[5]

B. Warnings, Precautions, and Contraindications

The prescribing information for Zepatier includes several critical warnings and contraindications designed to mitigate the risk of serious adverse outcomes.

• FDA Black Box Warning: Risk of Hepatitis B Virus (HBV) Reactivation: This is the most significant safety warning associated with all HCV DAA therapies, including Zepatier. There have been post-marketing reports of HBV reactivation in patients with current or prior HBV infection who were treated with DAAs. Some of these cases have resulted in fulminant hepatitis, hepatic failure, and death. Consequently, the FDA mandates that all patients be tested for evidence of HBV infection (by measuring Hepatitis B surface antigen and Hepatitis B core antibody) before initiating treatment. Patients found to be co-infected must be monitored for hepatitis flare or HBV reactivation during and after HCV treatment.[6]
• Increased Risk of ALT Elevations: A notable precaution is the risk of delayed elevations in serum alanine aminotransferase (ALT) levels, which typically occur at or after treatment week 8. While these elevations are generally asymptomatic and resolve, they necessitate hepatic laboratory monitoring. The standard recommendation is to perform liver function tests prior to initiating therapy, at treatment week 8, and as clinically indicated thereafter. This risk has been observed to be higher in certain demographic groups, including females, patients of Asian descent, and individuals aged 65 or older, and is mechanistically linked to higher plasma concentrations of grazoprevir.[5]
• Contraindication in Hepatic Impairment: Zepatier is strictly contraindicated in patients with moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment. This contraindication is driven by the pharmacokinetics of the grazoprevir component. In patients with significant liver dysfunction, the metabolism of grazoprevir is impaired, leading to substantially elevated plasma concentrations. This increased exposure heightens the risk of drug-induced liver injury and ALT elevations, making the risk of treatment outweigh the potential benefits in this population.[6]

C. Drug-Drug Interaction Profile

The potential for clinically significant drug-drug interactions is a major consideration when prescribing Zepatier. These interactions are primarily driven by the fact that both elbasvir and grazoprevir are substrates of the CYP3A enzyme and the P-glycoprotein (P-gp) transporter. Additionally, grazoprevir is a substrate of the organic anion-transporting polypeptide 1B (OATP1B) transporter.[7]

Co-administration of Zepatier with drugs that strongly induce or inhibit these pathways can lead to altered plasma concentrations of elbasvir and grazoprevir, potentially resulting in loss of efficacy or increased toxicity.

Table 4: Clinically Significant Drug-Drug Interactions with Elbasvir/Grazoprevir

Drug Class	Interacting Drug(s)	Effect on Zepatier	Clinical Recommendation	Reference(s)
Anticonvulsants	Carbamazepine, Phenytoin	Significantly decreased plasma concentrations	Contraindicated	2
Antimycobacterials	Rifampin	Significantly decreased plasma concentrations	Contraindicated	6
Herbal Products	St. John's Wort	Significantly decreased plasma concentrations	Contraindicated	2
HIV Antiretrovirals	Efavirenz	Significantly decreased plasma concentrations	Contraindicated	2
	Atazanavir, Lopinavir, Saquinavir, Tipranavir	Significantly increased grazoprevir concentrations	Contraindicated	6
Immunosuppressants	Cyclosporine	Significantly increased grazoprevir concentrations	Contraindicated	6
	Tacrolimus	Increased tacrolimus concentrations	Monitor tacrolimus levels and adjust dose	5
Antifungals (Azoles)	Ketoconazole (strong CYP3A inhibitor)	Increased elbasvir/grazoprevir concentrations	Co-administration not recommended	5
HMG-CoA Reductase Inhibitors (Statins)	Atorvastatin, Rosuvastatin, Simvastatin, Lovastatin	Increased statin concentrations	Dose limitations and monitoring for myopathy required	5

VI. Regulatory and Commercial History

Elbasvir was developed and is marketed by Merck & Co. (known as MSD outside the United States and Canada) as part of the fixed-dose combination product Zepatier.[2] The regulatory and commercial strategy for Zepatier was shaped by the highly competitive landscape of HCV therapeutics in the mid-2010s.

Regulatory Approval Timeline

• United States (FDA): Merck submitted its New Drug Application (NDA 208261) for Zepatier to the U.S. Food and Drug Administration on May 28, 2015. Following a priority review, the FDA approved Zepatier on January 28, 2016, for the treatment of chronic HCV genotypes 1 and 4 in adults.[2] The indication was subsequently expanded to include pediatric patients 12 years of age and older.[5] The application was not referred to an FDA advisory committee, as the drug was not first-in-class and its safety profile was considered similar to other approved DAAs.[20]
• European Union (EMA): The European Commission granted marketing authorization for Zepatier on July 22, 2016. This approval allowed for marketing in all 28 EU member states as well as in the European Economic Area countries of Iceland, Liechtenstein, and Norway, with commercial launches beginning in late 2016 and early 2017.[29]

Post-Marketing Commitments

As part of its approval, the FDA required Merck to conduct post-marketing studies. These commitments included deferred pediatric studies to evaluate the long-term safety and efficacy in younger age groups and to conduct detailed phenotypic analyses of elbasvir against specific NS5A resistance mutations to further refine the understanding of viral resistance patterns.[20]

Market Context and Positioning

Zepatier entered a market that was already transformed by the arrival of highly effective DAAs, most notably Gilead Sciences' Sovaldi (sofosbuvir) and Harvoni (ledipasvir/sofosbuvir) and AbbVie's Viekira Pak.[27] Merck's strategy to gain market share was twofold. First, it competed aggressively on price, launching Zepatier with a list price of $54,600 for a 12-week course, which was substantially lower than the approximately $94,000 for Harvoni and $83,000 for Viekira Pak. This move initiated a price war that helped to increase patient access and reduce the overall cost burden of HCV treatment.[27]

Second, Merck leveraged the robust clinical data from its development program to establish a clear niche of clinical superiority in specific patient populations. The compelling results of the C-SURFER trial, in particular, positioned Zepatier as the standard of care for patients with HCV and severe chronic kidney disease.[7] While Zepatier's narrower genotypic coverage was a competitive disadvantage against later pangenotypic regimens like Mavyret (glecaprevir/pibrentasvir) and Epclusa (sofosbuvir/velpatasvir), its strong evidence base in difficult-to-treat populations and its competitive pricing secured it a durable and important place in the HCV treatment armamentarium.[26]

VII. Synthesis and Concluding Remarks

Elbasvir, as an integral component of the fixed-dose combination Zepatier, represents a significant advancement in the treatment of chronic Hepatitis C. Its development and clinical application exemplify the era of direct-acting antivirals, which have transformed HCV from a chronic, difficult-to-manage illness into a curable disease for the vast majority of patients.

The primary strengths of elbasvir lie in its high potency against its target, the HCV NS5A protein, which translates into excellent clinical efficacy. When combined with grazoprevir, it achieves cure rates well over 90% for genotypes 1 and 4. Its simple, once-daily oral administration and generally favorable tolerability profile have greatly improved the patient experience compared to older interferon-based regimens. The most defining strength of the elbasvir/grazoprevir regimen is its proven safety and efficacy in patient populations with high unmet needs, particularly those with severe chronic kidney disease (including on dialysis) and individuals with HIV co-infection. Its pharmacokinetic profile, with negligible renal clearance, makes it uniquely suited for these groups.

However, in the rapidly evolving landscape of HCV therapy, elbasvir's limitations have become more apparent. Its activity is largely confined to genotypes 1 and 4, which is a significant disadvantage compared to the simplicity and broad utility of pangenotypic regimens that are now widely available. Furthermore, the need for baseline NS5A resistance testing in genotype 1a patients adds a layer of complexity and cost to the treatment algorithm, a step that is not required for most other modern DAA regimens.

In conclusion, the place of elbasvir in contemporary clinical practice has become more specialized. While pangenotypic regimens such as glecaprevir/pibrentasvir and sofosbuvir/velpatasvir are now considered the first-line standard of care for most patients due to their convenience and broad coverage, the elbasvir/grazoprevir combination retains a vital role. It remains an excellent, evidence-based, and often preferred option for patients with genotype 1 or 4 infection who also have severe renal impairment or for whom other agents may be contraindicated due to drug interactions. Historically, its entry into the market was also pivotal, as its competitive pricing strategy helped to disrupt the high cost of DAA therapy, thereby broadening access to curative treatment for millions of patients worldwide.

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