RegulationBreakthrough Therapy (United States), Fast Track (United States), Orphan Drug (United States), Overseas New Drugs Urgently Needed in Clinical Settings (China), Priority Review (China)

Structure/Sequence

Molecular FormulaC22H29FN3O9P

InChIKeyTTZHDVOVKQGIBA-IQWMDFIBSA-N

CAS Registry1190307-88-0

View All Structures (2)

110

Clinical Trials associated with Ledipasvir/Sofosbuvir

NCT04460443

/ Unknown statusPhase 2/3IIT

Sofosbuvir Based Regimens in Treatment of COVID 19 Patients

Sofosbuvir containing treatment in treatment of COVID 19 Egyptian patients

Start Date01 Aug 2020

Sponsor / Collaborator

Tanta University

NCT04498936

/ CompletedPhase 4IIT

Efficacy of Adding Sofosbuvir/Ledipasvir Combination, or Nitazoxanide to the Standard of Care in Treatment of COVID-19: A Randomized Controlled Trial

The efficacy of treating COVID-19 infection by using Sofosbuvir/Ledipasvir and Nitazoxanide will be examined. Included patients will be into 3 groups. The 1st group will receive Sofosbuvir/Ledipasvir plus the standard care treatment (SCT). The 2nd group will take Nitazoxanide and SCT, while the 3rd group will receive only SCT. Then the clinical improvement and the rate of PCR change from positive to negative will be evaluated in each group.

Start Date15 Jul 2020

Sponsor / Collaborator

Assiut University

[+1]

NCT04530422

/ CompletedPhase 3IIT

Efficacy of Sofosbuvir Plus Ledipasvir in Egyptian Patients With COVID-19 Compared to Standard Treatment

Currently there is no known effective therapy or vaccine for treatment of SARS-CoV-2, highlighting urgency around identifying effective therapies.
This study aiming to evaluate the anti-HCV medications efficacy "Sofosbuvir-Ledipasvir" in treatment of moderate cases with SARS-COV-2 infection, in comparison to the standard treatment (hydroxychloroquine, oseltamivir and azithromycin).

Start Date15 Apr 2020

Sponsor / Collaborator-

100 Clinical Results associated with Ledipasvir/Sofosbuvir

100 Translational Medicine associated with Ledipasvir/Sofosbuvir

100 Patents (Medical) associated with Ledipasvir/Sofosbuvir

Literatures (Medical) associated with Ledipasvir/Sofosbuvir

01 May 2022·Journal of pediatric gastroenterology and nutrition

Ledipasvir‐sofosbuvir in Adolescents With Chronic Hepatitis C and Hematological Malignancies Undergoing Chemotherapy

Article

Author: Abdel‐Rahman Zekri ; Fatma S. Elsayed Ebeid ; Kathryn Kersey ; Anuj Gaggar ; Manal Hamdy El‐Sayed ; Benedetta Massetto ; Alaa El‐Haddad ; Walaa Elsayed ; Fangqiu Zhang

ABSTRACT:

Objectives::

In children with hematological malignancies, chronic hepatitis C virus (HCV) infection has been associated with more rapid liver disease progression and higher risk of malignancy relapse due to chemotherapy interruption. We evaluated the safety and efficacy of ledipasvir‐sofosbuvir for 12weeks in these patients.

Methods::

In a phase 2, open‐label study, at one site in Egypt, patients ages 12‐<18years with chronic HCV genotype 1 or 4 infection undergoing maintenance chemotherapy for hematological malignancies received ledipasvir‐sofosbuvir (90 mg/400 mg) once daily for 12weeks. The efficacy endpoint was sustained virologic response 12 weeks after treatment (SVR12). Safety was assessed by the incidence of adverse events and clinical and laboratory data, including HCV flares defined as alanine aminotransferase >3‐fold increase from Day 1 and HCV RNA elevation >1 × log10 from Day 1.

Results::

Of the 19 adolescents enrolled and treated, median age was 14 years (range 12–17), 84% (16/19) were male, and all had HCV genotype 4 and were HCV treatment naive. All patients completed treatment and achieved SVR12 (19/19, 100%, 95% confidence interval, 82–100). Common adverse events were pyrexia (5/19, 26%), diarrhea (4/19, 21%), and headache (4/19, 21%). Three patients experienced serious adverse events of pneumonia (two patients), and osteoarthritis and diarrhea (one patient); none were considered related to study drug. No patient experienced HCV flares.

Conclusions::

Ledipasvir‐sofosbuvir was well‐tolerated and efficacious in adolescents with chronic HCV genotype 4 and leukemia undergoing maintenance chemotherapy. These data support the use of this interferon and ribavirin‐free regimen in adolescents with hematological malignancies.

01 Dec 2021·JAMA internal medicineQ1 · MEDICINE

Patient and Payer Incentives to Use Patented Brand-Name Drugs vs Authorized Generic Drugs in Medicare Part D

Q1 · MEDICINE

Article

Author: Huskamp, Haiden A. ; Sarpatwari, Ameet ; Keating, Nancy L. ; Hansen, Richard A. ; Carrier, Michael A. ; Dusetzina, Stacie B.

Importance:

In response to scrutiny over high drug prices, manufacturers of insulin and direct-acting antiviral agents for treating hepatitis C have recently introduced authorized generic alternatives to their patented brand-name products. These authorized generic drugs have list prices at least 50% lower than the list price of the brand-name drugs, which should result in savings to patients. However, it is unclear whether these authorized generic drugs are offered on Medicare Part D formularies because they may not provide savings to plans or Medicare.

Objective:

To assess Medicare Part D formulary coverage for 4 brand-name formulations of insulin and direct-acting antiviral agents and their authorized generic formulations.

Design, Setting, and Participants:

This cross-sectional study used Medicare Prescription Drug Plan Formulary and Pricing Information Files from quarter 3 of 2020 and Medicare Part D plan enrollment for September 2020. Four patented brand-name drugs (sofosbuvir and velpatasvir fixed-dose combination tablets [Epclusa], ledipasvir and sofosbuvir tablets [Harvoni], insulin lispro [Humalog], and insulin aspart [Novolog]) and their authorized generic formulations for all Part D stand-alone prescription drug plans (n = 959) and Medicare Advantage prescription drug plans (n = 3148) were studied.

Main Outcomes and Measures:

Beneficiary-weighted formulary coverage of brand-name and authorized generic products; beneficiary out-of-pocket costs; and prerebate plan, manufacturer, and Medicare spending on brand-name and authorized generic products.

Results:

In quarter 3 of 2020, 97% of beneficiaries were in plans that covered brand-name drugs only or both brand-name and authorized generic drugs; approximately 3% were in plans that covered authorized generic drugs only. Observed authorized generic drug list prices were 67%, 62%, and 50% lower than list prices for Epclusa, Harvoni, and each brand-name insulin product, respectively. Medicare beneficiaries using authorized generic drugs could save $270 per year for 12 vials of Humalog and $2974 for a full course of Harvoni. Plans, however, have limited incentives to encourage authorized generic drug use because rebates for brands likely exceed savings available with authorized generic drugs, particularly for beneficiaries with spending that reaches the Medicare Part D coverage gap.

Conclusions and Relevance:

The results of this cross-sectional study suggest that authorized generic drugs for insulin and direct-acting antiviral agents may lower out-of-pocket spending for patients but are unlikely to provide savings for Part D plans or Medicare. Instead, these drugs allow manufacturers to offer products at a lower list price without materially lowering net prices or profits.

01 Dec 2021·JPMA. The Journal of the Pakistan Medical AssociationQ4 · MEDICINE

Assessment of outcome for sample of Iraqi patients with chronic hepatitis C virus infection treated by Ledipasvir/sofosbuvir drug.

Q4 · MEDICINE

Article

Author: AlBayati, Sabeha Moosa ; Faraj, Osama Abdulrahman

OBJECTIVE:

To evaluate the response to treatment by the new directly acting antivirals drugs Sofosbuvir and Ledipasvir (Harvoni), on Iraqi patients diagnosed with hepatitis C infection genotype1 and genotype 4.

METHODS:

This prospective study was conducted in the Gastroenterology unit of Al- Yarmouk Teaching Hospital, Baghdad, Iraq, from February 2019 to February 2020. Included were one hundred patients diagnosed with hepatitis C by antibody test and viral load. All non-cirrhotic participants received a drug containing 400 mg sofosbuvir /90 mg ledipasvir once daily for 12 weeks, whereas the cirrhotics had to take it for 24 weeks. Lab. Investigations and viral load were assessed at baseline, and twelve weeks after end of treatment.

RESULTS:

The predominant genotype was 1 with 58 (58 %) patients whereas genotype 4 had 42 (42%) patients. Liver cirrhosis was present in 9(9%) patients and severe renal impairment in 27(27%) patients. Undetectable viral load at the end of treatment (week 12) was observed in 96 (96%) patients whereas 4 (4%) patients were reported as non-responders.

CONCLUSIONS:

Excellent therapeutic results were achieved with generic combination of sofosbuvir/ledipasvir. The regimen is highly effective and tolerable with the highest viral response observed in HCV patients with genotype 1and 4, inclusive of patients with chronic renal failure or cirrhosis.

News (Medical) associated with Ledipasvir/Sofosbuvir

23 Jul 2026

·www.biospace.com

Model Medicines to Present New Data on MDL-001 at ASV 2026: Broad-Spectrum Antiviral Activity Across Six Viral Families

Oral presentation unifies the respiratory and hepatic programs. The first-in-class, direct-acting, broad-spectrum, Thumb-1 polymerase inhibitor demonstrates single-agent activity against influenza, RSV, SARS-CoV-2, HCV, HBV, and HDV, including activity against oseltamivir-resistant influenza and oral in vivo proof-of-concept. SAN DIEGO — Model Medicines , an AI-first biotechnology company developing first-in-class therapeutics against multi-indication biological choke points, today announced that it will present new preclinical data at the 45th Annual Meeting of the American Society for Virology ( ASV 2026 ), to be held July 27–30, 2026, on the University of Minnesota Twin Cities campus in Minneapolis, MN. The event is being supported by Gilead Sciences Foundation, Elanco, GSK, Roche, Moderna, and Cocrystal Pharma, among others. The oral presentation will be delivered by Daniel Haders, PhD, Founder and CEO of Model Medicines. The data advance MDL-001 toward two first-in-class therapeutic goals: a universal direct-acting antiviral for influenza-like illness (influenza, RSV, and coronaviruses) and a universal direct-acting antiviral for chronic hepatitis (hepatitis C, hepatitis B, and hepatitis D). The ASV presentation is the first to report both goals as a single cross-family dataset. ASV 2026 Oral Presentation Presenter: Daniel Haders, PhD, Founder and CEO, Model Medicines Title: MDL-001, an oral Thumb-1 polymerase inhibitor, demonstrates broad-spectrum antiviral activity across six viral families with oral in vivo proof-of-concept Workshop: W44 — Antiviral Therapies II Program Number: W44-3 Abstract ID: 4518354 Date: July 29, 2026 Time: 7:00–7:15 PM CT (workshop session: 6:30–8:00 PM CT) Location: Room PWB 2-470, Phillips-Wangensteen Building Authors: Daniel Haders, Virgil Woods, Tyler Umansky, Sean Russell, Asha Goodman, Michael Bobardt, Briana McGovern, Kris M. White, Adolfo García-Sastre, William Brubaker, Philippe Gallay, Davey Smith Affiliations: Model Medicines; Scripps Research; Icahn School of Medicine at Mount Sinai; Farmington Pharma Development; University of California, San Diego. Each winter, clinicians face a recurring tripledemic of influenza, RSV, and SARS-CoV-2 that imposes hundreds of millions of infections and hundreds of thousands of deaths worldwide every year. [1] In a non-pandemic year in the U.S. alone, adults experience two to six of these respiratory viral illnesses and children approximately six to eight, at an economic cost exceeding $100 billion. [2] , [3] Despite this recurring toll, no single-agent antiviral is approved to treat the annual convergence of the tripledemic, and the world is no better prepared for the next respiratory pandemic than it was for the last. Chronic viral hepatitis is a health crisis of comparable scale. Hepatitis B and C infections persist in 254 million and 58 million people worldwide, respectively. [4] An estimated 5–15 million carry both viruses at once, yet most will never be diagnosed. Only 13% of HBV infections and 36% of HCV infections are identified globally, and fewer than 1% of co-infected patients know their status. Co-infection is not merely additive. Patients carrying both viruses are over 100-fold more likely to develop hepatocellular carcinoma than uninfected individuals. [5] Compounding the danger, every FDA-approved HCV direct-acting antiviral (DAA) carries a boxed warning for the risk of hepatitis B virus (HBV) reactivation in patients with current or prior HBV infection. This reactivation can lead to fulminant hepatitis, liver failure, or death. This FDA-mandated warning, added in 2016, applies to all DAA regimens, such as Epclusa, Harvoni, Mavyret, and others. Together, these gaps point to a single, persistent, and largely unaddressed need: one oral agent with broad-spectrum, direct-acting activity across the RNA viruses that drive both crises. For forty years, that molecule has been considered impossible to build. MDL-001 is designed to meet that need. It is the first direct-acting, non-nucleoside antiviral shown to be potent across multiple RNA virus families, and the first therapeutic of any mechanism to match or exceed multiple approved standards of care across RNA virus families in preclinical models. Its activity across both acute respiratory and chronic hepatic infection, combined with oral bioavailability, favorable pharmacokinetics, and a clean preclinical safety profile, positions the compound as a potential first-in-class therapy that could collapse multiple fragmented treatment paradigms into one. Model Medicines has reported the respiratory and hepatic arms of the MDL-001 program separately over the past year at IDWeek 2025 [6] , AASLD 2025 [7] , HepDART 2025 [8] , CROI 2026 [9] , ESCMID Global 2026 [10] , SERVC 2026 [11] and EASL 2026 [12] . “MDL-001 is the first Thumb-1 inhibitor to demonstrate antiviral activity across six viral families,” said Daniel Haders, PhD, Founder and CEO of Model Medicines. “The field held that allosteric pockets on viral polymerases diverge too rapidly to support cross-family targeting. Our work shows the RdRp Thumb-1 pocket is conserved and cryptic, and that the right chemistry engages it across families. ASV convenes the virologists best equipped to interrogate that claim, and we look forward to the discussion in Minneapolis.” The American Society for Virology is the largest virology society in the world. ASV meetings are among the largest and most important virology conferences globally, providing a forum for discussion and collaboration among scientists working across all aspects of virology, from basic research to vaccines and antiviral therapeutics. Program details are available at . About the Target: RdRp Thumb-1, A Conserved and Druggable Allosteric Target Conventional scientific wisdom holds that allosteric sites on viral polymerases diverge too rapidly to enable broad-spectrum direct-acting antiviral (DAA) development. Model Medicines overturned this assumption by demonstrating the structural conservation of the RNA-dependent RNA polymerase (RdRp) Thumb-1 allosteric pocket across viral families. The Thumb-1 site governs an essential mechanism for viral replication. The Thumb-1 pocket interacts with the viral Λ1-loop to control an indispensable conformational change required for polymerase initiation. Viruses cannot abandon this mechanism without sacrificing their replicative fitness. This target discovery is the biological foundation for Model Medicines’ Virology Program. Data on RdRp Thumb-1 can be found here . The corresponding preprint can be found here . About MDL-001: Discovery and Preclinical Profile Model Medicines utilized its AI-driven GALILEO™ platform to discover novel broad-spectrum inhibitor chemistry for this target within a multi-scaffold Markush structure. The research team trained GALILEO™ on a proprietary dataset spanning multiple viral families. This training enabled the model to learn the structural and chemical features required for broad-spectrum Thumb-1 inhibition. A library of potent inhibitors has been discovered, reduced to practice, and validated. Specifically, MDL-001 is the first DAA shown to be potent against multiple viral families in vitro: Orthomyxoviridae, Pneumoviridae, Coronaviridae, Flaviviridae, Kolmioviridae, and Hepadnaviridae. MDL-001 has demonstrated multi-log antiviral efficacy against influenza, SARS-CoV-2, HCV, and HBV in animal models. Furthermore, in vivo results demonstrate superiority or equivalence to multiple standards of care, including sofosbuvir, oseltamivir, remdesivir, and nirmatrelvir. Model Medicines plans to Investigational New Drug (IND) application with the FDA for MDL-001 in 2027. The full preclinical data readout can be found here . The corresponding preprint can be found here . About GALILEO™ GALILEO™ is Model Medicines’ proprietary, peer-reviewed, end-to-end multimodal generative AI drug discovery platform designed to discover and de-risk therapeutics against challenging and "undruggable" biological targets. Powered by Built-for-Purpose datasets and an ensemble of generative AI and zero-shot models, GALILEO™ integrates target discovery, tera-scale ultra-large virtual screening, ADMET prediction, compound synthesis, and automated lead optimization. By leveraging 3D protein structure data and strict chemical novelty metrics, the platform enables early, high-confidence compound prioritization with industry-leading prospective hit rates and exceptional chemical novelty. GALILEO™ powers Model Medicines' internal pipeline, including lead candidates MDL-001 and MDL-4102. The platform was validated through peer-reviewed publication in the American Chemical Society (ACS) journal Chemical Research in Toxicology. About Model Medicines Model Medicines is an AI-first biotechnology company engineering first-in-class small molecules that target the biological linchpins underlying disease. The company’s research spans infectious disease, oncology, and inflammation, with programs designed around conserved molecular choke points that drive multiple pathologies. Model Medicines has discovered a direct-acting, non-nucleoside, broad-spectrum antiviral (MDL-001) and a potent, selective, and novel BRD4 inhibitor (MDL-4102). Its work demonstrates how large-scale computation can uncover entirely new classes of drugs once thought unreachable. Model Medicines is advancing a new generation of therapeutics that redefine what is possible in modern drug discovery. Learn more at . Media Contact Patrick O’Neill Head of Partnerships & Investor Relations media@modelmedicines.com [1] Luong QXT, Hoang PT, Ho PT, Ayun RQ, Lee TK, Lee S. Potential broad-spectrum antiviral agents: a key arsenal against newly emerging and reemerging respiratory RNA viruses. Int J Mol Sci. 2025;26:1481. [2] Rossignol JF. Rethinking methods used to evaluate effectiveness of therapeutics for COVID-19 and other viral respiratory illnesses. Future Virol. 2022;17:67-69. [3] Hanage, W. P., & Schaffner, W. (2025). Burden of Acute Respiratory Infections Caused by Influenza Virus, Respiratory Syncytial Virus, and SARS-CoV-2 with Consideration of Older Adults: A Narrative Review. Infectious diseases and therapy, 14(Suppl 1), 5–37. [4] World Health Organization. Global hepatitis report 2024: action for access in low- and middle-income countries. Geneva: WHO; 2024. [5] Mavilia MG, Wu GY. HBV-HCV coinfection: viral interactions, management, and viral reactivation. J Clin Transl Hepatol. 2018;6:296-305. [6] MDL-001: A Broad-Spectrum Antiviral Targeting the Thumb-1 Domain of Viral Polymerases, Open Forum Infectious Diseases, Volume 13, Issue Supplement_1, January 2026, ofaf695.084, [7] MDL-001 As A Next Generation HCV Thumb-1 inhibitor With Clinical-Stage Safety, The Liver Meeting: 2025 Abstracts. (2025). Hepatology (Baltimore, Md.), 82(S1), S1–S2308. Abstract 0088. [8] Oral Thumb-1 polymerase inhibitor MDL-001 achieves preclinical HCV and HBV proof-of-concept, including HCV/HBV co-infection and equivalence to sofosbuvir. Paper presented at: HEPDART 2025; December 7–11, 2025 . [9] MDL-001, a novel oral thumb-1 polymerase inhibitor, shows efficacy in HCV/HBV in vitro and in vivo. Paper presented at: Conference on Retroviruses and Opportunistic Infections (CROI); February 22–25, 2026; Denver, CO. Abstract 589. [10] MDL-001, an oral direct-acting Thumb-1 polymerase inhibitor, demonstrates broad-spectrum activity against influenza viruses, respiratory syncytial virus, and SARS-CoV-2 with oral proof-of-concept in mice. Abstract presented at: ESCMID Global 2026; April 18, 2026; Munich, Germany. Abstract 5803 . MDL-001, an oral direct-acting Thumb-1 polymerase inhibitor, demonstrates single-agent efficacy against HCV/HBV co-infection in vitro, and achieves HCV and HBV preclinical proof-of-concept. Abstract presented at: ESCMID Global 2026; April 18, 2026; Munich, Germany. Abstract 5778. [11] MDL-001, an oral direct-acting Thumb-1 polymerase inhibitor, demonstrates broad-spectrum activity against influenza viruses, respiratory syncytial virus, and SARS-CoV-2 with oral proof-of-concept in mice. Paper presented at: The 18th Southeastern Regional Virology Conference (SERVC 2026), April 24–26, 2026 [12] MDL-001, an oral direct-acting Thumb-1 polymerase inhibitor, demonstrates efficacy against HCV/HBV co-infection in vitro, and achieves HCV and HBV preclinical proof-of-concept, including equivalence to sofosbuvir, Journal of Hepatology, Volume 84, Supplement 1, May 2026, Pages S877-S878, THU-580. (26)02352-4/abstract

Clinical Study

27 Apr 2026

·www.biospace.com

Model Medicines to Present at SERVC 2026: MDL-001, a Universal Direct-Acting Antiviral for Respiratory and Hepatic Viral Infections

Oral presentation highlights first-in-class Thumb-1 polymerase inhibitor with broad-spectrum single-agent efficacy against influenza, RSV, SARS-CoV-2, HCV, HBV, and HDV SAN DIEGO — Model Medicines , an AI-first biotechnology company developing first-in-class therapeutics against multi-indication biological choke points, today announced that it will present new preclinical data at the 18th Southeastern Regional Virology Conference ( SERVC 2026 ), to be held April 24–26, 2026, at the Emory Hotel & Conference Center in Atlanta, GA. The oral presentation will be delivered by Virgil Woods, PhD, Senior Scientist at Model Medicines. The data advance MDL-001 toward two first-in-class therapeutic goals: a universal direct-acting antiviral for influenza-like illness (influenza, RSV, and coronaviruses) and a universal direct-acting antiviral for chronic hepatitis (hepatitis C, hepatitis B, and hepatitis D). SERVC 2026 Oral Presentation Presenter: Virgil Woods, PhD, Senior Scientist, Model Medicines Title: MDL-001, an oral direct-acting Thumb-1 polymerase inhibitor, demonstrates broad-spectrum activity against influenza viruses, respiratory syncytial virus, and SARS-CoV-2 with oral proof-of-concept in mice Authors: Virgil Woods * , Tyler Umansky * , Sean M Russell, Asha Z Goodman, Michael Bobardt, Briana L McGovern, Romel Rosales, M Luis Rodriguez, Harm van Bakel, Emilia Mia Sordillo, Viviana Simon, Adolfo García-Sastre, Kris M White, William F Brubaker, Philippe Gallay, Davey Smith, Daniel Haders *These authors contributed equally. Each winter, clinicians face a recurring tripledemic of influenza, RSV, and SARS-CoV-2. These viral respiratory illnesses (VRIs) impose a massive global disease burden, with hundreds of millions of infections and hundreds of thousands of deaths annually [1] . In a non-pandemic year in the U.S., adults experience two to six VRIs and children approximately six to eight, with economic costs exceeding $100 billion [2] . There are currently no single-agent antivirals approved to treat this annual convergence of the tripledemic respiratory viruses. Chronic viral hepatitis is a health crisis of enormous proportions. An estimated 5–15 million people worldwide have both HBV and HCV infections. [3] , [4] Most will never be diagnosed. Only 13% of HBV infections and 36% of HCV infections are diagnosed globally. Fewer than 1% of co-infected patients know their status. [5] Current treatments for chronic hepatitis C possess a critical and potentially fatal vulnerability. Every FDA-approved HCV direct-acting antiviral (DAA) carries a black box warning for the risk of hepatitis B virus (HBV) reactivation in patients with current or prior HBV infection. This FDA-mandated warning, added in 2016, applies to all DAA regimens without interferon, such as Epclusa , Harvoni , Mavyret , and others. HBV reactivation in HCV co-infected patients can lead to fulminant hepatitis, liver failure, or even death. Together, these gaps point to a persistent and largely unaddressed need: a single agent with broad-spectrum, direct-acting antiviral activity. MDL-001 was discovered to meet that need. Demonstrated activity across both acute respiratory and chronic hepatic viral infections, combined with oral bioavailability, favorable pharmacokinetics, and demonstrated safety, positions the compound as a potential first-in-class therapy that could meaningfully improve multiple treatment paradigms. “For decades, the field treated a broad-spectrum, non-nucleoside DAA as an impossibility,” said Daniel Haders, PhD, Founder and CEO of Model Medicines. “The prevailing view was that allosteric pockets on viral polymerases drift too quickly to support cross-family targeting. Our work shows that the RdRp Thumb-1 pocket is, in fact, conserved across viral families, and that it can be drugged. We are looking forward to presenting the data to the SERVC community and to the discussion that follows.” The Southeastern Regional Virology Conference has been held every two years since 1990, and is one of the premier virology meetings in the United States. SERVC 2026 was organized by Mehul Suthar (Emory), Helen Lazear (UNC), Megan Stanifer (Florida), and Steeve Boulant (Florida), and convenes virologists across emerging viruses, immunity, DNA virus replication and latency, respiratory viruses (influenza, SARS, and zoonoses), retroviruses, flaviviruses, intestinal viruses, vaccines, and diagnostics. The 2026 program features keynote speaker Ileana Cristea (Princeton) and plenary speakers from the University of Georgia, University of Kentucky, UAB, LSU, Vanderbilt, and University of Florida. Program details are available at . About the Target: RdRp Thumb-1, A Conserved and Druggable Allosteric Target Conventional scientific wisdom holds that allosteric sites on viral polymerases diverge too rapidly to enable broad-spectrum direct-acting antiviral (DAA) development. Model Medicines overturned this assumption by demonstrating the structural conservation of the RNA-dependent RNA polymerase (RdRp) Thumb-1 allosteric pocket across viral families. The Thumb-1 site governs an essential mechanism for viral replication. The Thumb-1 pocket interacts with the viral Λ1-loop to control an indispensable conformational change required for polymerase initiation. Viruses cannot abandon this mechanism without sacrificing their replicative fitness. This target discovery is the biological foundation for the Model Medicines’ Virology Program. About MDL-001: Discovery and Preclinical Profile Model Medicines utilized its AI-driven GALILEO™ platform to discover novel broad-spectrum inhibitor chemistry for this target within a multi-scaffold Markush structure. The research team trained GALILEO™ on a proprietary dataset spanning multiple viral families. This training enabled the model to learn the structural and chemical features required for broad-spectrum Thumb-1 inhibition. A library of potent inhibitors has been discovered, reduced to practice and validated. Specifically, MDL-001 is the first DAA shown to be potent against multiple viral families in vitro: Orthomyxoviridae, Pneumoviridae, Coronaviridae, Flaviviridae, Kolmioviridae, and Hepadnaviridae. MDL-001 has demonstrated multi-log antiviral efficacy against influenza, SARS-CoV-2, HCV and HBV in animal models. Furthermore, in vivo results demonstrate superiority or equivalence to multiple standards of care, including sofosbuvir, oseltamivir, remdesivir, and nirmatrelvir. Model Medicines’ virology program, the discovery of the RdRp Thumb-1 site, and MDL-001 preclinical proof-of-concept data have been peer-reviewed, accepted and presented at IDWeek 2025 [6] , AASLD 2025 [7] , HepDART 2025, CROI 2026 [8] , and ESCMID Global 2026 [9] , [10] . The company will present additional data at SERVC 2026. The full preclinical data readout can be found here . Model Medicines plans to Investigational New Drug (IND) application with the FDA for MDL-001 in late 2026 and anticipates commencing clinical trials in 2027. About Model Medicines Model Medicines is an AI-first biotechnology company engineering first-in-class small molecules that target the biological linchpins underlying disease. The company’s research spans infectious disease, oncology, and inflammation, with programs designed around conserved molecular choke points that drive multiple pathologies. Model Medicines has discovered a direct-acting, non-nucleoside, broad-spectrum antiviral (MDL-001) and a potent, selective and novel BRD4 inhibitor (MDL-4102). Its work demonstrates how large-scale computation can uncover entirely new classes of drugs once thought unreachable. Model Medicines is advancing a new generation of therapeutics that redefine what is possible in modern drug discovery. Learn more at . Media Contact Patrick O’Neill Head of Partnerships & Investor Relations media@modelmedicines.com [1] Luong, Q. X. T., Hoang, P. T., Ho, P. T., Ayun, R. Q., Lee, T. K., & Lee, S. (2025). Potential broad-spectrum antiviral agents: A key arsenal against newly emerging and reemerging respiratory RNA viruses. International Journal of Molecular Sciences. [2] Rossignol J. F. (2021). Rethinking methods used to evaluate effectiveness of therapeutics for COVID-19 and other viral respiratory illnesses. Future virology, 10.2217/fvl-2021-0209. [3] Mavilia MG, Wu GY. HBV-HCV Coinfection: Viral Interactions, Management, and Viral Reactivation. J Clin Transl Hepatol. 2018 Sep 28;6(3):296-305. doi: 10.14218/JCTH.2018.00016. Epub 2018 Jul 6. PMID: 30271742; PMCID: PMC6160312. [4] Maqsood Q, Sumrin A, Iqbal M, Younas S, Hussain N, Mahnoor M, Wajid A. Hepatitis C virus/Hepatitis B virus coinfection: Current prospectives. Antivir Ther. 2023 Aug;28(4):13596535231189643. doi: 10.1177/13596535231189643. PMID: 37489502. [5] World Health Organization. Global hepatitis report 2024: action for access in low- and middle-income countries. Geneva: World Health Organization; 2024 Apr 9. 242 p [6] MDL-001: A Broad-Spectrum Antiviral Targeting the Thumb-1 Domain of Viral Polymerases, Open Forum Infectious Diseases, Volume 13, Issue Supplement_1, January 2026, ofaf695.084, [7] MDL-001 As A Next Generation HCV Thumb-1 inhibitor With Clinical-Stage Safety, The Liver Meeting: 2025 Abstracts. (2025). Hepatology (Baltimore, Md.), 82(S1), S1–S2308. [8] MDL-001, a novel oral thumb-1 polymerase inhibitor, shows efficacy in HCV/HBV in vitro and in vivo. Paper presented at: Conference on Retroviruses and Opportunistic Infections (CROI); February 22–25, 2026; Denver, CO. Abstract 589. [9] MDL-001, an oral direct-acting Thumb-1 polymerase inhibitor, demonstrates broad-spectrum activity against influenza viruses, respiratory syncytial virus, and SARS-CoV-2 with oral proof-of-concept in mice. Abstract presented at: ESCMID Global 2026; April 18, 2026; Munich, Germany. Abstract 5803. [10] MDL-001, an oral direct-acting Thumb-1 polymerase inhibitor, demonstrates single-agent efficacy against HCV/HBV co-infection in vitro, and achieves HCV and HBV preclinical proof-of-concept. Abstract presented at: ESCMID Global 2026; April 18, 2026; Munich, Germany. Abstract 5778.

siRNA

18 Nov 2025

·www.biospace.com

Before GLP-1s, a Great Pricing Battle Played Out in Hep C Market

iStock, SvetaZi The introduction of AbbVie’s hepatitis C drugs in 2014 forced Gilead’s hand in the fight for market dominance in hepatitis C. A similar dynamic is now playing out between Eli Lilly and Novo Nordisk in the obesity space, with some key differences. Almost 10 years before Novo Nordisk and Eli Lilly’s cutthroat battle for control of the obesity market, AbbVie and Gilead duked it out over a highly effective class of hepatitis C drugs. As Novo and Lilly’s drug prices come on full display in the deal announced at the White House earlier this month. This unprecedented moment, where Lilly and Novo are slashing the price of their GLP-1 drugs well before they have generic competition, had some experts looking back on the moment with Gilead and AbbVie—a same but different moment from the recent past. “It’s the closest analogy we have to this. But there’s some important differences,” Sarah Emond, CEO of drug pricing watchdog the Institute for Clinical and Economic Review (ICER), told BioSpace . So let’s go back to 2013. First on the scene in December of that year was Gilead with Sovaldi, which included the active ingredient sofosbuvir and showed high cure rates over a 12-week treatment course. The wholesale acquisition cost of the drug was $28,000 for a 28-pill bottle. “That was a situation where you had a $1,000 pill—$1,000 a day,” Morningstar analyst Karen Andersen remembered. (Gilead did offer an assistance program with a $5 co-pay for eligible patients.) Drug pricing How Effective Will TrumpRx and Other Direct-to-Consumer Drug Pricing Initiatives Be? With pricing pressures climbing, Pfizer, Eli Lilly and other major drugmakers are looking to sell their products directly to patients. Analysts are skeptical that these efforts, including those announced to much fanfare from the White House, will result in meaningful reductions in drug spending. November 12, 2025 · 11 min read · Tristan Manalac Read More The FDA approved a second Gilead hep C treatment just under a year later in October 2014 . Harvoni, a combination of sofosbuvir and ledipasvir, offered a shorter treatment time for patients with certain genotypes of the virus. Gilead did not announce the price at the time, but ICER said a 12-week course had a list price of $95,000. Gilead enjoyed wild market success—and blowback for the cost of the treatment. Then came AbbVie. AbbVie launched Viekira Pak months after Haravoni. “The minute you had a viable competitor—Gilead started seeing competition from AbbVie—that pricing went from . . . $80,000 or so to $20,000 for a cure,” Andersen said. In announcing the U.S. market approval of Viekira in December 2014, AbbVie noted the drug’s high cure rates and shorter duration of treatment. While a price was not named, Bloomberg News reported a list price of $83,319, a 12% discount to Gilead’s Harvoni. (Like Gilead, AbbVie offered patient assistance, promising access to Viekira Pak for just $5 a month.) Insurers quickly took note. A few days after the FDA’s greenlight, Express Scripts secured a discount to that price with AbbVie and offered to carry Viekira Pak over Harvoni, which would be dropped for most patients at the start of 2015. At the time, Express Scripts Chief Medical Officer Steve Miller noted that patients in France were paying $51,373 for Sovaldi, according to a report from FirstWord Pharma . Analysts projected $2.9 billion in first-year sales for Viekira Pak, which requires patients to take six pills a day instead of one. Gilead agreed to bring the price of Sovaldi and Harvoni down in February 2015, offering a 46% discount off the original list price. ICER revised its rating for the drugs to “high value” for most healthcare systems. Then-Gilead CEO John Milligan touted Harvoni’s superiority early on. “The market doesn’t think they are comparable. There’s a clear preference for Harvoni over the Viekira Pak,” Milligan said at a conference in June 2015. But trouble emerged in AbbVie’s franchise. One of Viekira Pak’s active ingredients, ribavirin, proved to be difficult for patients to tolerate. Common side effects included hemolytic anemia, itchiness, fatigue and upper respiratory symptoms. The ingredient was quickly recommended to be used only for the most severe cases of hep C . AbbVie updated the label for Viekira Pak in October 2015 to warn of liver risks and recommend closer patient monitoring. Meanwhile, the company kept working in the clinic on a better drug. AbbVie’s Mavyret, which dropped ribavirin in favor of a cocktail of an NS3/4A protease inhibitor glecaprevir and an NS5A inhibitor pibrentasvir, was approved in August 2017 . The drug, which rendered the virus undetectable in clinical trials, was developed with Enanta Pharmaceuticals . AbbVie listed the drug at $26,400 for an eight-week treatment. The drug decimated Gilead’s hep C sales, causing the company to lower its profit guidance for the franchise, according to a February 2018 report in Fierce Pharma . The price for Sovaldi was about $28,000 per month and Harvoni was $31,500, compared to Mavyret’s $13,500. The hep C franchise combined collected $3.7 billion, down from 9.1 billion the year prior, according to Gilead’s year-end 2018 earnings report. The company attributed the decline to lower average net selling price and lower volume of sales for Harvoni and other medicines in the portfolio “as a result of increased competition and lower patient starts.” By 2019, the company stopped reporting sales of the two drugs individually. AbbVie’s hep C franchise never reached anywhere near the heights of Gilead’s, with Mavyret peaking at $3.4 billion in 2018. Back to 2025 The hep C battle is the only time in recent memory that Andersen or Emond can remember price coming into play so early in a drug’s lifecycle. The typical path is for a branded medication to enjoy years of exclusive market success with a high price—unless, of course, a better rival drug comes along and supplants it. But typically, efficacy or some enhancement in the treatment paradigm is what changes the market, not price. These same dynamics are playing out right now between Novo and Lilly—two mega pharmas that aren’t strangers to mutual competition, Andersen said. But this time is different. Two weeks ago, both Novo and Lilly’s CEOs appeared at the White House to announce a drug pricing deal with President Donald Trump that would bring their GLP-1 medications down to around $350 per month. It wasn’t a huge change, as both companies have been offered direct-to-consumer (DTC) options for months that provide the drugs at a steep discount to the list prices. Lilly’s Zepbound initially had a list price of $1,059.87 per month when it launched at the end of 2023. Single-dose vials can now be purchased at Walmart through LillyDirect for $349 per month, according to a recent announcement . The current list price for Wegovy in the U.S. is $1,349.02 for a 28-day supply, according to Novo. But the manufacturer offers rebates that can bring down the cost to about $499 a month. As is typical for such DTC platforms, patients must pay out of pocket. While not all commercial insurance covers the weight loss medication, Novo says that through payers that do, patients may pay just $224 per month, or nothing at all. Emond said that the two markets are fairly similar, in that hep C and obesity are both public health priorities. Both market battles started with high list and net prices, with Novo enjoying first-entrant advantage early on. Even when Lilly entered the picture, the prices stayed high. .responsive-container { display: flex; flex-wrap: wrap; border: 1px solid #ededed; font-family: Helvetica, Arial, Sans-Serif; padding: 20px 20px 10px 20px; } .column-left { flex: 1; max-width: 45%; padding: 20px 20px 10px 20px; } .column-right { flex: 2; padding: 20px 20px 10px 20px; } @media (max-width: 768px) { .column-left, .column-right { max-width: 100%; flex: 100%; padding: 10px 0; } } Subscribe to BioPharm Executive! Market insights, trending business and policy stories for biopharma leaders hbspt.forms.create({ region: "na1", portalId: "4413123", formId: "7c139b3c-ff0b-44e0-bffe-f449801dca59", onFormSubmitted: function($form, data) { window.dataLayer = window.dataLayer || []; window.dataLayer.push({ 'event': 'GTMevent', 'event_name': 'newsletter_sign_up' }); } }); “Both drugs are wildly cost effective. And a similar thing happened with the hepatitis C drugs, as we saw competition come in,” Emond said. But with GLP-1s, both the U.S. government and private insurance companies are largely declining to cover treatment for the weight loss treatments, leading to a fast-moving consumer market where patients self-pay for access. Meanwhile, the pharmas have been contending with significant pressure from the Trump administration to lower prices across their portfolios, with the president particularly targeting the weight loss drugs. “For years they’ve been competing in diabetes and they’ve been competing in obesity. So there’s already in the backdrop that typical competition for them,” Andersen said. “But the more policy side of this, and just the lack of insurance coverage, I think, are the things that made this very primed for significant reform of the direct-to-consumer side and seeing these lower prices.” Hep C is also a one-time treatment that is potentially curative, whereas GLP-1s require long-term maintenance dosing. “These obesity medicines are for a chronic condition likely needing to be taken for a lifetime and so that represents a little bit different math when you think about budget impact,” Emond said. At ICER, he added, “that’s where we’re all spending our time, trying to think about how to introduce these drugs in an affordable way.” ICER has determined that the obesity drugs are cost-effective—a strong vote of confidence for any treatment in pharma. The problem is that the potential market is just so huge that affordability means something completely different when it comes to weight loss medications. “It’s not that they’re not priced to value—they are. It’s just that the number of eligible patients makes it really hard to introduce them in an affordable way,” Emond said. “We continue to just have a lot of firsts when it comes to the obesity medicines for us as a drug pricing ecosystem.”

Drug ApprovalAcquisition

100 Deals associated with Ledipasvir/Sofosbuvir

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KEGG	Wiki	ATC	Drug Bank
-	Ledipasvir/Sofosbuvir	J05AP51	-

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Viremia	Japan	Gilead Sciences, Inc.	03 Feb 2025
Hepatitis C	Japan	Gilead Sciences, Inc.	03 Jul 2015
Hepatitis C, Chronic	European Union	Gilead Sciences Ireland UC	17 Nov 2014
Hepatitis C, Chronic	Iceland	Gilead Sciences Ireland UC	17 Nov 2014
Hepatitis C, Chronic	Liechtenstein	Gilead Sciences Ireland UC	17 Nov 2014
Hepatitis C, Chronic	Norway	Gilead Sciences Ireland UC	17 Nov 2014
Chronic hepatitis C genotype 1	United States	Gilead Sciences, Inc.	10 Oct 2014

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Coinfection	Phase 3	Canada	Gilead Sciences, Inc.	01 Apr 2016
HIV Infections	Phase 3	United States	Gilead Sciences, Inc.	01 Apr 2016
HIV Infections	Phase 3	Canada	Gilead Sciences, Inc.	01 Apr 2016
Cryoglobulinemia	Phase 3	United States	Gilead Sciences, Inc.	01 Feb 2016
Decompensated cirrhosis of liver	Phase 3	Canada	Gilead Sciences, Inc.	01 Jan 2016
Chronic hepatitis C genotype 2	Phase 3	Taiwan Province	Gilead Sciences, Inc.	22 Dec 2015
Hepatitis B	Phase 3	Taiwan Province	Gilead Sciences, Inc.	22 Dec 2015
Hepatitis B, Chronic	Phase 2	United States	Gilead Sciences, Inc.	01 Feb 2018
Porphyria Cutanea Tarda	Phase 2	United States	Gilead Sciences, Inc.	06 Sep 2017
Kidney Failure, Chronic	Phase 2	United States	Gilead Sciences, Inc.	27 Jun 2017

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03118674 (CTgov)	Phase 2	Porphyria Cutanea Tarda \| Hepatitis C, Chronic	23	Harvoni	sftpdfjggm = tdschyrkzy bvolqzitpo (stxhazpsgq, aqgzbpygsm - tzpakcnkyb) View more	-	03 Jul 2023
NCT02868242 (Pubmed)	Phase 2	Hematologic Neoplasms Maintenance	19	Ledipasvir-sofosbuvir	czfmgofulx(zklwcrhmzg) = 4/19, 21% dfnbqhwafo (ldbrysyxmn ) View more	Positive	10 Feb 2022
NCT03312023 (APOSTLE, CTgov)	Phase 2	Hepatitis B, Chronic \| Hepatitis B	21	Ledipasvir 90 MG / Sofosbuvir 400 MG Oral Tablet [Harvoni] (Group A (LDV/SOF for Low Replicative HBV))	xnfgakkaws(midxvkjuax) = izdolsvmmi uqhwemnrss (akolqmdlco, 0.2) View more	-	25 Aug 2021
NCT03312023 (APOSTLE, CTgov)	Phase 2	Hepatitis B, Chronic \| Hepatitis B	21	Ledipasvir 90 MG / Sofosbuvir 400 MG Oral Tablet [Harvoni] (Group B (LDV/SOF for Viral Suppressed HBV))	xnfgakkaws(midxvkjuax) = ezfgozmelr uqhwemnrss (akolqmdlco, 0.3) View more	-	25 Aug 2021
NCT02533934 (STOP-CO, CTgov)	Phase 4	Fibrosis \| HIV Infections \| Hepatitis C ... View more	68	SOF (Adults With HIV and Chronic HCV and End-stage Liver Disease (ESLD) Pre-liver Transplant)	iriwqbcpvo = lqprsbxnpk jrdkstefuc (dqzjfbrepz, wqlaraxbkx - raoyglcuis) View more	-	02 Feb 2021
NCT02533934 (STOP-CO, CTgov)	Phase 4	Fibrosis \| HIV Infections \| Hepatitis C ... View more	68	SOF (Adults With HIV With Chronic HCV and Any Stage of Liver Disease Post-liver Transplant)	iriwqbcpvo = igsyrnxpsd jrdkstefuc (dqzjfbrepz, vvqvjksmom - reisnmwffz) View more	-	02 Feb 2021
NCT02591277 (Pubmed \| J Viral Hepat)	Not Applicable	Chronic hepatitis C genotype 1	3,294	Ledipasvir/sofosbuvir	tllokgkwup(ilkaockpqo) = pyfwcqsdrp qakawqgdio (wkotzenhzs ) View more	-	01 Jan 2021
NCT02825212 (CTgov)	Phase 2/3	Hepatitis C \| Cryoglobulinemia	10	Sofosbuvir+Ledipasvir+Velpatasvir (Epclusa)	gevbotjags = eplxdfrjub vgzdbeuovh (duiqbzrtpr, kynbdtsdxg - itzazpmgmf) View more	-	17 Dec 2020
NCT02858180 (CTgov)	Phase 4	Pulmonary Disease, Chronic Obstructive \| Heart Failure \| Lung Diseases, Interstitial ... View more	15	Sofosbuvir/ledipasvir fixed dose combination(SOF/LDV FDC) (Heart Failure Cohort)	aylkbcgzaq = tnqxfaophg shkioheyyr (uexgewxrnk, tgkfdrskiw - irpomeqtme) View more	-	21 Apr 2020
NCT02858180 (CTgov)	Phase 4		15	Sofosbuvir/ledipasvir fixed dose combination(SOF/LDV FDC) (Lung Disease Cohort)	aylkbcgzaq = vlyokvkasx shkioheyyr (uexgewxrnk, awvrqhizgq - hnobliztgb) View more	-	21 Apr 2020
NCT02503735 (CTgov)	Not Applicable	Proteinuria \| Hepatitis C \| Chronic Kidney Diseases	14	Sofosbuvir/Ledipasvir FDC	vvvpadzfni(njqeaisukv) = csjzhyyyzd wxbxyfnmfu (spnacdfzhz, ojgdnixjhi - aawqssuhld) View more	-	09 Jan 2020
NCT02707601 (Pubmed \| PLoS One)	Phase 3	-	150	Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF)	zrkagsnaei(bfkgcqexbo) = pyqeogoprm zkktnkhwev (eksbhdqamb, 93 - 99) View more	-	01 Jan 2020
NCT02707601 (Pubmed \| PLoS One)	Phase 3	-	150	Rilpivirine/F/TAF (R/F/TAF)	scwuqoqsta(fvddxuzjhg) = ewmmmosixc zqwfptdqdm (cswskntpfp )	-	01 Jan 2020
IAS2020	Not Applicable	-	868	Ledipasvir/sofosbuvir	ikiyallhww(corxccbaxh) = qdagposssn lzdkbjvoko (zzwtapznga )	-	01 Jan 2020

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