VIR-2218 Demonstrates Dose-Dependent and Durable Reductions of Hepatitis B Surface Antigen in Phase 1/2 Trial
Interim results from the ongoing Phase 2 trial demonstrate that VIR-2218 results in a significant dose-dependent and durable reduction in hepatitis B surface antigen (HBsAg) through Week 24 in patients with chronic HBV who received two doses of VIR-2218, ranging from 20 mg to 200 mg. Similar HBsAg reductions were observed in both HBeAg- and HBeAg+ patients. In addition, VIR-2218 was generally well tolerated, with the majority of treatment emergent adverse events (AEs) reported as mild in severity, and no clinically significant alanine transaminase (ALT) elevations observed.
“The rapid and sustained dose-dependent knockdown of surface antigen observed in this trial with only 2 doses of VIR-2218 is impressive,” said Edward
By targeting a conserved region of the HBV genome, VIR-2218 is designed to inhibit the production of all HBV proteins, including HBsAg. Suppression of HBV proteins, particularly HBsAg, is hypothesized to remove the inhibition of T and B cell activity directed against HBV. VIR-2218 was the first siRNA in the clinic to include
Dose-dependent HBsAg reductions in HBV patients
In the ongoing Phase 2 trial, virally suppressed patients on nucleos(t)ide reverse transcriptase inhibitor therapy (n=24) received two subcutaneous 20, 50, 100, or 200 mg doses of VIR-2218 on Day 1 and Day 29. At Week 24, the mean change in HBsAg observed with 20, 50, 100, and 200 mg was -0.76 log10, -0.93 log10, -1.23 log10, and -1.43 log10, respectively. Of note, all patients who received the 200 mg dose level achieved a ≥1 log10 reduction in HBsAg, with HBeAg- and HBeAg+ patients achieving similar mean declines. There has been no dose-related trend in the frequency of AEs observed during the trial, with the most common AE being headache (n=6; 25%). No patients discontinued the trial due to an AE.
ESC+ design suggests a potentially improved hepatic safety profile
The Alnylam ESC+ technology incorporated into VIR-2218 is designed to reduce off-target binding while maintaining on-target activity, which is hypothesized to result in an improved hepatic safety profile. In analyses of the in vitro, in vivo and Phase 1 clinical data, the ESC+ siRNA VIR-2218, when compared to the parent compound ALN-HBV, which is not an ESC+ siRNA, was shown to have:
- Improved in vitro specificity by reducing off-target effects on host messenger RNA;
- Decreased propensity to cause ALT elevations in a humanized liver chimeric mouse model; and
- In a cross-study comparison of Phase 1 data, decreased propensity to cause ALT elevations in healthy volunteers at dose levels anticipated to be clinically relevant.
Information on the potential hepatic safety profile of all siRNAs is an important consideration in the HBV patient population, especially those with advanced liver disease.
“We are pleased that the data from our VIR-2218 Phase 1/2 clinical trial continue to support the potential of this molecule to be the backbone of a treatment regimen aimed at the functional cure of chronic HBV infection,” said
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About Hepatitis B
Approximately 290 million people globally are chronically infected with HBV and approximately 900,000 of them die from HBV-associated complications each year. There is a significant unmet medical need for more effective therapies that lead to life-long control of the virus after a finite duration of therapy, which is the definition of a functional cure. For a registrational trial to demonstrate a functional cure, the formal endpoint accepted by the
VIR-2218 is a subcutaneously administered HBV-targeting siRNA that has the potential to stimulate an effective immune response and have direct antiviral activity against HBV. It is the first siRNA in the clinic to include Enhanced Stabilization Chemistry Plus (ESC+) technology to enhance stability and minimize off-target activity, which potentially can result in an increased therapeutic index. VIR-2218 is the first asset in the company’s collaboration with
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This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as “may,” “will,” “expect,” “plan,” “anticipate,” “estimate,” “intend,” “potential” 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 potential benefits of VIR-2218, the timing of VIR-2218 clinical trials, the potential of ESC+ technology to enhance the safety of siRNAs and statements regarding the potential benefits of Vir’s collaboration with
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Source: Vir Biotechnology, Inc.