Bepirovirsen (GSK836)

China [CN]

Bepirovirsen (GSK836) Key Information

Generic Name: Bepirovirsen  Chinese Name: 贝皮罗韦森 / 贝匹罗韦森  Development Code: GSK3228836, GSK836, IONIS-HBVRx, ISIS 505358  CAS Number: 1403787-62-1  Molecular Formula: C₂₁₄H₂₆₉N₆₉O₁₃₁P₂₀S₂₀ (oligonucleotide sequence)  Molecular Weight: ~7344 Da  Originator/Collaborator: Ionis Pharmaceuticals (discovery), GlaxoSmithKline (GSK, development)

Drug Type and Mechanism of Action

Drug Type: Antisense oligonucleotide (ASO, Gapmer), Hepatitis B virus (HBV) gene silencing agent

Triple Mechanism of Action:

Targeted degradation of viral RNA: Specifically binds to HBV mRNA/pgRNA, recruits RNase H to degrade viral RNA, blocking HBsAg, HBeAg, and viral DNA synthesis

Inhibition of viral replication: Reduces viral pre-genomic RNA, lowering HBV DNA levels

Immune activation: Breaks immune tolerance through TLR8 agonism, restarting the host antiviral immune response

Chemical Modification: 2'-O-methoxyethyl (2'-MOE) + phosphorothioate backbone, enhancing stability, liver targeting, and extending half-life

Core Clinical Application (2026)

Indications: Chronic Hepatitis B (CHB) (adults, HBeAg positive/negative, receiving/not receiving nucleoside/nucleotide analog (NA) treatment)

Core Goal: Functional cure (≥24 weeks after discontinuation: HBsAg clearance + undetectable HBV DNA)

Dosage Regimen: 300 mg, subcutaneous injection, once weekly for 24 weeks (limited course, not lifelong)

Key Clinical Data (Phase III B-Well 1/2):

Significantly improved functional cure rate when combined with standard treatment (vs. standard treatment alone)

Baseline HBsAg ≤ 1000 The group receiving IU/mL showed the most significant benefits.

Good safety profile, no new safety signals observed.

Market launch progress: Global regulatory submissions (FDA/EMA/NMPA) to begin in Q1 2026, with approval expected in the second half of 2026.

Physicochemical and supply chain highlights:

Appearance: White to off-white solid (API)

Solubility: Water-soluble (for injection)

Stability: Store dry and sealed at 4°C

Product type: Active Pharmaceutical Ingredient (API), reference standard, intermediate

Purity: Pharmaceutical grade ≥ 98%

HS Code: 2934999090

Compliance: Granted FDA Fast Track designation, CDE Breakthrough Therapy designation, and Japanese SENKU designation; protected by patents.