Ledipasvir/Sofosbuvir Is Effective as Sole Treatment of Porphyria Cutanea Tarda with Chronic Hepatitis C.

BACKGROUND AND AIMS: Chronic hepatitis C [CHC] is a risk factor for porphyria cutanea tarda [PCT]. To assess whether ledipasvir/sofosbuvir is effective for treating both PCT and CHC, we treated patients with CHC + PCT solely with ledipasvir/sofosbuvir and followed them for at least 1 year to assess cure of CHC and remission of PCT. METHODS: Between September 2017 and May 2020, 15 of 23 screened PCT + CHC patients were eligible and enrolled. All were treated with ledipasvir/sofosbuvir at recommended doses and durations, according to their stage of liver disease. We measured plasma and urinary porphyrins at baseline and monthly for the first 12 months and at 16, 20, and 24 mos. We measured serum HCV RNA at baseline, 8-12, and 20-24 mos. Cure of HCV was defined as no detectable serum HCV RNA ≥ 12 weeks after the end of treatment (EOT). Remission of PCT was defined clinically as no new blisters or bullae and biochemically as urinary uro- plus hepta-carboxyl porphyrins ≤ 100 mcg/g creatinine. RESULTS: All 15 patients, 13 of whom were men, were infected with HCV genotype 1. 2/15 withdrew or were lost to follow-up. Of the remaining 13, 12 achieved cure of CHC; 1 had complete virological response, followed by relapse of HCV after ledipasvir/sofosbuvir but was subsequently cured by treatment with sofosbuvir/velpatasvir. Of the 12 cured of CHC, all achieved sustained clinical remission of PCT. CONCLUSIONS: Ledipasvir/sofosbuvir [and likely other direct-acting antivirals] is an effective treatment for HCV in the presence of PCT and leads to clinical remission of PCT without additional phlebotomy or low-dose hydroxychloroquine treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT03118674.

Direct-Acting Antiviral Use for Genotype 1b Hepatitis C Patients with Associated Hematological Disorders from Romania.

Background and objectives: this study assessed variations in the blood parameters of patients with hematological disorders infected with HCV throughout a 12-week interferon-free treatment regimen. Materials and methods: We followed a total of 344 patients suffering from chronic hepatitis C, infected with the 1b genotype and concomitant hematological disorders, who benefited from the direct-acting antiviral (DAA) therapy in our clinic. Seven of the most routinely checked blood parameters were analyzed, namely, hemoglobin, leucocyte count, neutrophils, erythrocyte count, platelet count, ALT, and total bilirubin level. In total, 129 patients received a treatment scheme comprising ombitasvir, paritaprevir, ritonavir, and dasabuvir, while the 215 other patients received a sofosbuvir and ledipasvir regimen. Results: Patients enrolled in the study showed remarkably increased ALT levels in the first four weeks of DAA treatment, normalizing to levels below 40 U/L by the end of regimen. There were no other blood parameters that worsened throughout the 12-week regimen to levels below our laboratory's normal range. After 12 weeks of DAA therapy, 309 patients (90%) achieved SVR. Conclusions: Our findings are consistent in evaluating the efficacy and tolerability of direct-acting antivirals for 1b genotype HCV infected patients with associated hematological malignancies under remission, and other hematological disturbances, that were previously unsuccessfully treated with a pegylated interferon regimen. Thus, paving a pathway for government-funded programs being implemented in this direction.

Effectiveness of Sofosbuvir, Ledipasvir/Sofosbuvir, or Paritaprevir/Ritonavir/Ombitasvir and Dasabuvir Regimens for Treatment of Patients With Hepatitis C in the Veterans Affairs National Health Care System.

BACKGROUND & AIMS: We investigated the real-world effectiveness of sofosbuvir, ledipasvir/sofosbuvir, and paritaprevir/ritonavir/ombitasvir and dasabuvir (PrOD) in treatment of different subgroups of patients infected with hepatitis C virus (HCV) genotypes 1, 2, 3, or 4. METHODS: We performed a retrospective analysis of data from 17,487 patients with HCV infection (13,974 with HCV genotype 1; 2131 with genotype 2; 1237 with genotype 3; and 135 with genotype 4) who began treatment with sofosbuvir (n = 2986), ledipasvir/sofosbuvir (n = 11,327), or PrOD (n = 3174), with or without ribavirin, from January 1, 2014 through June 20, 2015 in the Veterans Affairs health care system. Data through April 15, 2016 were analyzed to assess completion of treatments and sustained virologic response 12 weeks after treatment (SVR12). Mean age of patients was 61 ± 7 years, 97% were male, 52% were non-Hispanic white, 29% were non-Hispanic black, 32% had a diagnosis of cirrhosis (9.9% with decompensated cirrhosis), 36% had a Fibrosis-4 index score >3.25 (indicator of cirrhosis), and 29% had received prior antiviral treatment. RESULTS: An SVR12 was achieved by 92.8% (95% confidence interval [CI], 92.3%-93.2%) of subjects with HCV genotype 1 infection (no significant difference between ledipasvir/sofosbuvir and PrOD regimens), 86.2% (95% CI, 84.6%-87.7%) of those with genotype 2 infection (treated with sofosbuvir and ribavirin), 74.8% (95% CI, 72.2%-77.3%) of those with genotype 3 infection (77.9% in patients given ledipasvir/sofosbuvir plus ribavirin, 87.0% in patients given sofosbuvir and pegylated-interferon plus ribavirin, and 70.6% of patients given sofosbuvir plus ribavirin), and 89.6% (95% CI 82.8%-93.9%) of those with genotype 4 infection. Among patients with cirrhosis, 90.6% of patients with HCV genotype 1, 77.3% with HCV genotype 2, 65.7% with HCV genotype 3, and 83.9% with HCV genotype 4 achieved an SVR12. Among previously treated patients, 92.6% with genotype 1; 80.2% with genotype 2; 69.2% with genotype 3; and 93.5% with genotype 4 achieved SVR12. Among treatment-naive patients, 92.8% with genotype 1; 88.0% with genotype 2; 77.5% with genotype 3; and 88.3% with genotype 4 achieved SVR12. Eight-week regimens of ledipasvir/sofosbuvir produced an SVR12 in 94.3% of eligible patients with HCV genotype 1 infection; this regimen was underused. CONCLUSIONS: High proportions of patients with HCV infections genotypes 1-4 (ranging from 75% to 93%) in the Veterans Affairs national health care system achieved SVR12, approaching the results reported in clinical trials, especially in patients with genotype 1 infection. An 8-week regimen of ledipasvir/sofosbuvir is effective for eligible patients with HCV genotype 1 infection and could reduce costs. There is substantial room for improvement in SVRs among persons with cirrhosis and genotype 2 or 3 infections.

Cure with ledipasvir/sofosbuvir for chronic hepatitis C virus in an individual with gastric bypass.

WHAT IS KNOWN AND OBJECTIVE: The impact of gastric bypass surgery on the pharmacokinetics of various medications has been reported. Presently, no data exist for the treatment of chronic hepatitis C virus with ledipasvir/sofosbuvir (LDV/SOF) in an individual with a history of gastric bypass. CASE DESCRIPTION: We report the successful cure of an individual who was treated with LDV/SOF who had a history of gastric bypass. The patient tolerated LDV/SOF well while only experiencing a minor headache. WHAT IS NEW AND CONCLUSION: Ledipasvir/sofosbuvir treatment may still be effective in those with a history of gastric bypass surgery.

Curing the historically incurable: treatment success with ledipasvir/sofosbuvir for chronic hepatitis C virus in a heavily treatment-experienced individual.

WHAT IS KNOWN AND OBJECTIVE: Significant progression in the treatment of chronic hepatitis C virus has been made with the introduction of direct-acting antivirals (DAAs). However, limited data are available for the retreatment of individuals who have failed multiple prior DAAs. CASE DESCRIPTION: We report a single case of an individual who was unsuccessfully treated with five prior hepatitis C virus treatment regimens including simeprevir plus sofosbuvir who was successfully cured after treatment with ledipasvir/sofosbuvir. WHAT IS NEW AND CONCLUSION: Ledipasvir/sofosbuvir may be an option for treating patients who have failed multiple prior DAA regimens; however, further research is warranted.

Comparison of Glecaprevir/Pibrentasvir and Sofosbuvir/Ledipasvir in Patients with Hepatitis C Virus Genotype 1 and 2 in South Korea.

Background/Aims: This study compared the effectiveness and safety of glecaprevir/pibrentasvir (GLE/PIB) and sofosbuvir/ledipasvir (SOF/LDV) in real-life clinical practice. Methods: The data from genotype 1 or 2 chronic hepatitis C patients treated with GLE/PIB or sofosbuvir + ribavirin or SOF/LDV in South Korea were collected retrospectively. The analysis included the treatment completion rate, sustained virologic response at 12 weeks (SVR12) test rate, treatment effectiveness, and adverse events. Results: Seven hundred and eighty-two patients with genotype 1 or 2 chronic hepatitis C who were treated with GLE/PIB (n=575) or SOF/LDV (n=207) were included in this retrospective study. The baseline demographic and clinical characteristics revealed significant statistical differences in age, genotype, ascites, liver cirrhosis, and hepatocellular carcinoma between the GLE/PIB and SOF/LDV groups. Twenty-two patients did not complete the treatment protocol. The treatment completion rate was high for both regimens without statistical significance (97.7% vs. 95.7%, p=0.08). The overall SVR12 of intention-to-treat analysis was 81.2% vs. 80.7% without statistical significance (p=0.87). The overall SVR12 of per protocol analysis was 98.7% vs. 100% without statistical significance (p=0.14). Six patients treated with GLE/PIB experienced treatment failure. They were all male, genotype 2, and showed a negative hepatitis C virus RNA level at the end of treatment. Two patients treated with GLE/PIB stopped medication because of fever and abdominal discomfort. Conclusions: Both regimens had similar treatment completion rates, effectiveness, and safety profiles. Therefore, the SOF/LDV regimen can also be considered a viable DAA for the treatment of patients with genotype 1 or 2 chronic hepatitis C.

Evaluating Post-Market Adverse Events of The New Hepatitis C Therapies Using FEARS Data.

Background: Little is known regarding the safety of direct-acting antivirals (DAA), even though they are widely used. This study aims to evaluate the adverse events of DAA using post-market data. Methods: FDA Adverse Events Reporting System (FAERS) data from January 2019 through December 2019 were analyzed. FERAS reports in which the suspected drug contained the DAA drugs were extracted and included in the analysis. Univariable and bivariable analyses were performed in this study. Results: Most of the reported side effects were non-serious (62%). The number of times the drug was reported as ineffective was significantly higher while using Harvoni vs. Mavyret (32.14% vs. 1.05%) (p-value < 0.0001). On the other hand, hospitalization was significantly more reported while using Mavyret compared to Harvoni (52.02% vs. 22.45%) (p-value < 0.0001). Liver cancer was significantly more reported while using Harvoni vs. Mavyret (7.65% vs. 1.20%) (p-value < 0.0001). No significant difference in death cases was reported while using both drugs. Conclusion: Depending on the FDA Adverse Events Reporting System (FAERS) database, most of the non-serious adverse effects were headache and fatigue. There was no significant difference in cases of death reported while using both drugs. Liver cancer was more reported while using Harvoni. Hospitalization was more reported while using Mavyret.

Paronychia Associated with Ledipasvir/Sofosbuvir for Hepatitis C Treatment.

We present a case of medication-associated paronychia involving multiple toenails in a patient undergoing hepatitis C (HCV) therapy with ledipasvir/sofosbuvir. The patient was treated conservatively with topical mupirocin, clobetasol ointment, and acetic acid soaks, resulting in symptom improvement and control. This topical regimen was maintainined throughout the remaining weeks of the patient's antiviral course, with complete symptom resolution occurring only after completion of his ledipasvir/sofosbuvir treatment.

Sexual Dysfunction in a Patient Taking Ledipasvir/Sofosbuvir for the Treatment of Hepatitis C: A Case Report.

Sexual dysfunction is a bothersome side effect of several medications, though it has not yet been reported with the use of ledipasvir/sofosbuvir for the treatment of hepatitis C. However, sexual dysfunction is a potentially unrecognized side effect of ledipasvir/sofosbuvir that could result in nonadherence and treatment failure. We report a case of a 42-year-old man with a sudden onset of sexual dysfunction with the initiation of ledipasvir/sofosbuvir for the treatment of hepatitis C. The patient had no prior history or risk factors for the development of sexual dysfunction. His symptoms resolved upon discontinuation of ledipasvir/sofosbuvir after a successful 12-week course. Clinicians should be aware that sexual dysfunction is a possible side effect of ledipasvir/sofosbuvir and educate patients appropriately. Adherence should be emphasized as the risks of untreated hepatitis C virus far outweigh transient sexual dysfunction.

Efficacy and safety of sofosbuvir-ledipasvir for treatment of a cohort of Egyptian patients with chronic hepatitis C genotype 4 infection.

BACKGROUND AND AIMS: Treatment of hepatitis C virus (HCV) infection has significantly changed during the last few years. The combination of ledipasvir and sofosbuvir has been shown to treat high proportions of patients with HCV genotype 1 with remarkable tolerability. The aim of the work was to assess the efficacy and safety of sofosbuvir plus ledipasvir in treating treatment-naïve Egyptian patients with genotype 4 HCV infection. PATIENTS AND METHODS: In this open-label randomized study, 200 treatment-naive patients who were HCV antibody positive and HCV RNA positive by polymerase chain reaction, aged >18 years, were enrolled. The patients were classified into two groups: group I included 100 patients who received single therapy with sofosbuvir plus ledipasvir for 12 weeks and group II included 100 patients who received sofosbuvir plus oral weight-based ribavirin for 24 weeks. The primary end point was a sustained virological response at 12 weeks (SVR12) after the end of treatment, determined by quantitative polymerase chain reaction for HCV RNA. RESULTS: Group I patients showed statistically significant (p<0.05) higher SVR12 compared with group II patients (99% vs. 80%). There was no statistical difference (p>0.05%) between the studied groups regarding the frequencies of the side effects (26% vs. 29%). The most common adverse effects were headache, fatigue, myalgia, and cough. CONCLUSION: Sofosbuvir and ledipasvir treatment for 12 weeks was well tolerated by patients with HCV genotype 4 and resulted in 99% SVR for all patients who received 12 weeks of the study drugs. ClinicalTrials.gov Identifier: NCT02992457.

Treatment of Chronic Hepatitis C Virus Infection With Crushed Ledipasvir/Sofosbuvir Administered via a Percutaneous Endoscopic Gastrostomy Tube.

INTRODUCTION: Ledipasvir/sofosbuvir (Harvoni®) is a fixed-dose tablet indicated for the treatment of chronic hepatitis C virus (HCV) infection. There are currently no data available on the safety and efficacy of crushed ledipasvir/sofosbuvir tablets. CASE SUMMARY: This report describes the first documented case of successful treatment of chronic HCV infection in a patient crushing ledipasvir/sofosbuvir for administration via a percutaneous endoscopic gastrostomy (PEG) tube. The patient was treatment experienced and had evidence of compensated cirrhosis. Treatment duration was 24 weeks, and HCV RNA was undetectable 12 weeks after completion of treatment (SVR12) which is the accepted measure of a clinical cure. DISCUSSION: Issues may arise during or prior to starting HCV treatment that necessitate crushing tablets. Stopping or interrupting HCV treatment could lead to development of resistance or treatment failure. CONCLUSION: This is the first published case in which crushed ledipasvir/sofosbuvir administered via a PEG tube is documented as a safe and effective option for treatment of chronic HCV infection.

ε-MnO2-modified graphite electrode as a novel electrochemical sensor for the ultrasensitive detection of the newly FDA approved Hepatitis C antiviral drug ledipasvir.

A novel, simple and sensitive electrochemical method for the determination of ledipasvir (LED), the newly FDA approved Hepatitis C antiviral drug was developed and validated using ε-MnO2-modified graphite electrode. Two different MnO2 polymorphs (γ- and ε-MnO2 nanoparticles) were synthesized and characterized using X-ray powder diffraction (XRD), Fourier transform infrared (FTIR), energy dispersive X-ray (EDX) and thermogravimetric analysis (TGA). Surface area measurements show that ε-MnO2 NPs have large surface area of 345 m2/g, which is extremely high if compared to that of γ-MnO2 NPs (38 m2/g). In addition, a comprehensive study of the difference in the electrochemical behavior of LED while using pencil graphite electrode (PGE) modified with either γ- or ε-MnO2 NPs is carried out. It was found that surface area and percentage of surface hydroxyls of MnO2 NPs are the key factors governing the sensitivity of the fabricated electrode toward the oxidation of the positively charged LED. Scanning electron microscopy (SEM) was employed to investigate the morphological shape of MnO2 NPs and the surface of the bare and modified electrodes. Moreover, cyclic voltammetry and electrochemical impedance spectroscopy (EIS) were used for the surface analysis of the modified electrodes. Based on the obtained results, ε-MnO2/PGE was applied as a selective and sensitive electrode for determination of LED. Under the optimized experimental conditions, ε-MnO2/PGE provides a linear response over the concentration range of 0.025-3.60 µmol L-1 LED with a low limit of detection, which was found to be 5.10 nmol L-1 (4.50 ng mL-1) for the 1st peak and 9.20 nmol L-1 (8.10 ng mL-1) for the 2nd one. In addition, the oxidation behavior of LED is discussed with a full investigation of the oxidized product using FT-IR and LC/MS. The fabricated sensor exhibits a good precision, selectivity and stability and was applied successfully for the determination of LED in its tablets and real rat plasma samples with a good recovery using a simple extraction technique.

A facile synthesis of 3D NiFe2O4 nanospheres anchored on a novel ionic liquid modified reduced graphene oxide for electrochemical sensing of ledipasvir: Application to human pharmacokinetic study.

Novel and sensitive electrochemical sensor was fabricated for the assay of anti-HCV ledipasvir (LEDV) in different matrices. The designed sensor was based on 3D spinel ferromagnetic NiFe2O4 nanospheres and reduced graphene oxide (RGO) supported by morpholinium acid sulphate (MHS), as an ionic liquid (RGO/NSNiFe2O4/MHS). This sensor design was assigned to synergistically tailor the unique properties of nanostructured ferrites, RGO, and ionic liquid to maximize the sensor response. Electrode modification prevented aggregation of NiFe2O4, increasing electroactive surface area and allowed remarkable electro-catalytic oxidation of LEDV with an enhanced oxidation response. Differential pulse voltammetry was used for detection LEDV in complex matrices whereas; cyclic voltammetry and other techniques were employed to characterize the developed sensor properties. All experimental factors regarding sensor fabrication and chemical sensing properties were carefully studied and optimized. Under the optimum conditions, the designated sensor displayed a wide linear range (0.4-350 ng mL-1) with LOD of 0.133 ng mL-1. Additionally, the proposed sensor demonstrated good selectivity, stability and reproducibility, enabling the quantitative detection of LEDV in Harvoni® tablets, human plasma and in a pharmacokinetic study. Our findings suggest that the developed sensor is a potential prototype material for fabrication of high-performance electrochemical sensors.

A case of non-arteritic anterior ischemic optic neuropathy after completion of Harvoni therapy.

PURPOSE: To report the first reported case of non-arteritic anterior ischemic optic neuropathy (NAION) associated with the use of Harvoni (Gilead Sciences, Foster City, CA, USA), a newly approved treatment for Hepatitis C. OBSERVATIONS: We report a case of NAION in a hepatitis C patient who completed Harvoni therapy just prior to presentation. Harvoni was suspected to be the causative agent given a lack of NAION risk factors in an otherwise healthy young patient. CONCLUSIONS AND IMPORTANCE: NAION is an acute, painless vision loss that typically affects adults over 50. The mechanism of NAION remains uncertain although numerous associations have been identified including certain medications. Harvoni, a combination drug of ledipasvir/sofosbuvir, is a recently FDA-approved treatment for Hepatitis C. To date, however, no ophthalmological side effects have been reported with its use. Continued surveillance of patients treated with Harvoni will be needed to determine if additional events are observed in the future.

Considerations on bringing warehoused HCV patients into active care following interferon-free, direct-acting antiviral drug approval.

OBJECTIVES: Until recently, lack of efficacious and tolerable hepatitis C virus (HCV) treatments prompted patient warehousing until better treatment options became available. We investigated whether the introduction of ledipasvir/sofosbuvir precipitated patient return to clinics, thereby changing HCV clinic dynamics. METHODS: Online questionnaire responses indicated the volume of HCV patients followed, the proportion of warehoused patients and those who were proactively offered new options, methods for identifying and contacting patients, and insurance authorization/reimbursement-related information. RESULTS: Of 168 practices surveyed, 19% indicated no patient warehousing in the previous 3 years; 81% had warehoused 40% of patients; 92% were able to handle their patient load; and 82% had not changed practices to accommodate more HCV patients in the previous 12 months. Of the 35% of patients who were ledipasvir/sofosbuvir-eligible, 50% already completed/are completing therapy, 21% were not treated due to insurance denial, and 19% were awaiting responses from insurance companies. CONCLUSIONS: Launch of a new treatment did not overburden HCV practices. Patients eligible to receive new treatments were being treated, but pre-authorization processes and reimbursement denials reduced the numbers of treated patients.

Decreasing racial disparity with the combination of ledipasvir-sofosbuvir for the treatment of chronic hepatitis C.

African Americans (AA) in the US are twice as likely to be infected with hepatitis C virus (HCV) compared to the non-Hispanic-white US population (Cau). They are also more likely to be infected with HCV genotype 1, more likely to develop hepatocellular carcinoma, and, in addition, have a lower response rate to interferon-based therapies. With the increase in response rates reported for combinations of direct-acting antivirals, the possibility that racial disparity would be eliminated by agents that directly inhibit virus replication has become a reality. The objective of this review is to evaluate the literature from clinical studies and retrospective analysis with respect to the response of AA to the most prescribed antiviral combination sofosbuvir plus ledipasvir. While few studies have focused on AA patients, sufficient information is availed from the literature and studies in our predominately AA clinic population to confirm that ledipasvir-sofosbuvir has a similar effectiveness in AA as compared to Cau.

Synthesis of the first novel pyrazole thioglycosides as deaza ribavirin analogues.

This study reports a novel and efficient method for the synthesis of the first reported novel class of thiopyrazoles and their corresponding thioglycosides. These series of compounds were designed through the reaction of hydrazine derivatives with sodium dithiolate salt 2 in EtOH at ambient temperature to give the corresponding sodium 5-amino-4-cyano-1H-pyrazole-3-thiolates 4a-d. The latter compounds were treated with α-acetobromoglucose 6a and α-acetobromogalactose 6b in DMF at ambient temperature to give in an excellent yields the corresponding pyrazole S-glycosides 7a-h. Ammonolysis of the pyrazole thioglycosides 7a-h afforded the corresponding free thioglycosides 8a-h.

Safety analysis of sofosbuvir and ledipasvir for treating hepatitis C.

INTRODUCTION: The approval of sofosbuvir (SOF), a nucleotide analogue NS5B polymerase inhibitor, and ledipasvir (LDV), a NS5A inhibitor, marked a new chapter in IFN and ribavirin-free treatment of hepatitis C virus (HCV). This drug reduces adverse events associated with IFN therapy. AREAS COVERED: The purpose of this paper is to evaluate the safety and efficacy of LDV/SOF. Clinical trials illustrating safety and efficacy of LDV/SOF are reviewed and compared to other IFN and ribavirin-free treatment options available. EXPERT OPINION: In trials enrolling more than 3000 patients, LDV/SOF is well tolerated with a good safety and side-effect profile in diverse cohorts, including previous direct-acting antiviral (DAA) treatment failures, liver transplant recipients, decompensated cirrhosis and HIV/HCV co-infection. As with all DAAs, the potential for drug-drug interactions must be carefully evaluated, as demonstrated by recent post-marketing reports of symptomatic bradycardia when LDV/SOF is co-administered with amiodarone. Currently, dose recommendations cannot be given for patients with advanced renal disease. Trials in this population are ongoing, more study is warranted. When surveying the DAA regimens available, efficacy, safety and tolerability of LDV/SOF is comparable or better, and LDV/SOF provides an option with convenient single-tablet, once daily, ribavirin-free dosing with relatively few significant drug-drug interactions.

Finding Truth in a World Full of Spin: Myth-Busting in the Case of Sovaldi.

PURPOSE: Public discourse regarding the hepatitis C virus (HCV) drug Sovaldi® (sofosbuvir) has become inflamed, generating much heat but little light concerning the clinical, health economic, and quality-of-life merits of Sovaldi®. The purpose of this article is to provide a factual basis for evaluating the claims regarding the benefits of Sovaldi® relative to its costs. METHODS: A comprehensive review was conducted of news stories highlighted in the daily updates of the electronic newsletters BIO SmartBrief, FiercePharma, FierceBiotech and BioCentury Extra published from November 1, 2013, through December 31, 2014, on the topics of the HCV market, Sovaldi®, and other HCV therapeutics. Also reviewed were recent practice guidelines on the management of HCV infections, prescribing information on all HCV drugs approved by the US Food and Drug Administration, and health technology assessments of Sovaldi® and Harvoni(TM) (sofosbuvir/ledipasvir). FINDINGS: Sovaldi® and Harvoni(TM) have provided significant improvements in the treatment of HCV, with all-oral regimens and cure rates exceeding 90% in some populations of patients with HCV. Sovaldi® prevents significant health care resource utilization in patients who would otherwise develop cirrhosis and require a liver transplant; however, only a small proportion of patients with HCV develop cirrhosis, and fewer require liver transplants. Because it is not possible to identify those patients whose HCV will progress to severe liver disease, it would be necessary to treat a large number of patients with HCV to prevent disease progression in this subpopulation, resulting in a considerable loss to health plans even over a 20-year horizon. The claim that treating all patients with HCV with Sovaldi® would cost nearly as much as the current total US expenditure on all prescription drugs, while factually correct, is not a realistic scenario. Many patients with HCV will continue to go undiagnosed. In addition, the medical expense for those who are treated will be spread out over many years. However, the unexpectedly large, up-front cost of covering these drugs has had a major impact on health plan budgets, resulting in losses for some plans. IMPLICATIONS: Sovaldi® represents an enormous advance in the care of some populations of HCV-infected patients, but also a major cost burden to health plans. As the first of a number of anticipated, paradigm-changing drugs to treat medical conditions affecting large patient populations, Sovaldi® should act as a wake-up call for all health care stakeholders to engage in a meaningful, fact-based discussion about managing the cost of innovative new drugs to balance the needs of drug manufacturers, health plans, providers, and, above all, patients.