Gilead and Vir Biotechnology Establish Clinical Collaboration to Explore Combination Strategies for Functional Cure for Chronic Hepatitis B Virus
-- First Phase 2 Clinical Trial to Combine Immunomodulation and Antigen Suppression Approaches in
The companies plan to initiate a Phase 2 trial evaluating combination therapy for both treatment-experienced and treatment-naïve people living with HBV. The multi-arm trial will evaluate different combinations of selgantolimod, Gilead’s investigational TLR-8 agonist; VIR-2218, Vir’s investigational small interfering ribonucleic acid (siRNA); and a commercially-sourced, marketed PD-1 antagonist. People in the trial with HBV treatment experience may also receive Gilead’s Vemlidy® (tenofovir alafenamide fumarate, TAF). The primary outcome of the study will be the proportion of patients achieving a functional cure, defined as an off-therapy loss of hepatitis B surface antigen (HBsAg) and HBV DNA from the serum.
Both companies retain full rights to their individual product candidates and will discuss the potential path forward for any future combination studies based on the outcome of the Phase 2 trial.
“Gilead has a two-decade commitment to people with hepatitis B and we have worked tirelessly to bring new treatments forward with the goal of helping to improve their lives,” said
“We are enthusiastic about this collaboration,” said
HBV affects more than 290 million people worldwide. Globally, HBV is a leading cause of liver cancer and each year it is estimated that more than 800,000 people die of HBV-related liver disease. While current antiviral therapies result in sustained HBV viral suppression, they rarely completely clear the virus and therefore people with HBV require lifelong therapy.
The safety and efficacy of selgantolimod and VIR-2218 have not been established. They are investigational compounds, not approved by the
IMPORTANT SAFETY INFORMATION
BOXED WARNING: POST TREATMENT SEVERE ACUTE EXACERBATION OF HEPATITIS B
- Discontinuation of anti-hepatitis B therapy, including VEMLIDY, may result in severe acute exacerbations of hepatitis B. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue anti-hepatitis B therapy, including VEMLIDY. If appropriate, resumption of anti-hepatitis B therapy may be warranted.
Warnings and Precautions
- Risk of Development of HIV-1 Resistance in HBV/HIV-1 Coinfected Patients: Due to this risk, VEMLIDY alone should not be used for the treatment of HIV-1 infection. Safety and efficacy of VEMLIDY have not been established in HBV/HIV-1 coinfected patients. HIV antibody testing should be offered to all HBV-infected patients before initiating therapy with VEMLIDY, and, if positive, an appropriate antiretroviral combination regimen that is recommended for HBV/HIV-1 coinfected patients should be used.
- New Onset or Worsening Renal Impairment: Cases of acute renal failure and Fanconi syndrome have been reported with the use of tenofovir prodrugs. In clinical trials of VEMLIDY, there have been no cases of Fanconi syndrome or proximal renal tubulopathy (PRT). Patients with impaired renal function and/or taking nephrotoxic agents (including NSAIDs) are at increased risk of renal-related adverse reactions. Discontinue VEMLIDY in patients who develop clinically significant decreases in renal function or evidence of Fanconi syndrome. Monitor renal function in all patients – See Dosage and Administration.
- Lactic Acidosis and Severe Hepatomegaly with Steatosis: Fatal cases have been reported with the use of nucleoside analogs, including tenofovir DF. Discontinue VEMLIDY if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity develop, including hepatomegaly and steatosis in the absence of marked transaminase elevations.
Most common adverse reactions (incidence ≥5%; all grades) were headache, abdominal pain, cough, back pain, fatigue, nausea, arthralgia, diarrhea, and dyspepsia.
- Coadministration of VEMLIDY with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of tenofovir and the risk of adverse reactions.
- Coadministration of VEMLIDY is not recommended with the following: oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, or St. John’s wort. Such coadministration is expected to decrease the concentration of tenofovir alafenamide, reducing the therapeutic effect of VEMLIDY. Drugs that strongly affect P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) activity may lead to changes in VEMLIDY absorption.
Consult the full prescribing information for VEMLIDY for more information on potentially significant drug interactions, including clinical comments.
Dosage and Administration
- Testing Prior to Initiation: HIV infection.
- Prior to or when initiating, and during treatment: On a clinically appropriate schedule, assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein in all patients. In patients with chronic kidney disease, also assess serum phosphorus.
- Dosage in Adults: 1 tablet taken once daily with food.
- Renal Impairment: Not recommended in patients with end stage renal disease (ESRD; eCrCl <15 mL/min) who are not receiving chronic hemodialysis; in patients on chronic hemodialysis, on hemodialysis days, administer VEMLIDY after completion of hemodialysis treatment.
- Hepatic Impairment: Not recommended in patients with decompensated (Child-Pugh B or C) hepatic impairment.
VEMLIDY is indicated for the treatment of chronic hepatitis B virus (HBV) infection in adults with compensated liver disease.
Please click here to see full Prescribing Information for VEMLIDY, including BOXED WARNING.
Gilead Forward-Looking Statements
This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including the risk that Gilead may not realize the potential benefits of the collaboration with
Vir Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as “aim,” “will,” “may,” “potential,” “plan,” “promising” and similar expressions (as well as other words or expressions referencing future events, conditions, or circumstances) are intended to identify forward-looking statements. These forward-looking statements are based on Vir’s expectations and assumptions as of the date of this press release. Each of these forward-looking statements involves risks and uncertainties. Actual results may differ materially from these forward-looking statements. Forward-looking statements contained in this press release include statements regarding the clinical collaboration between Vir and
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