Peptide News Digest

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Regulatory · View digest

Gilead Hepcludex (Bulevirtide-gmod) FDA Accelerated Approval (May 22): First and Only US Treatment for Chronic Hepatitis Delta Virus, 47-Amino-Acid Lipopeptide NTCP Entry Inhibitor

The FDA granted accelerated approval on May 22, 2026 to Gilead Sciences' Hepcludex (bulevirtide-gmod) 8.5 mg, the first and only approved US treatment for adults living with chronic hepatitis delta virus (HDV) infection. Bulevirtide — formerly known as Myrcludex B — is a 47-amino acid, N-terminally myristoylated lipopeptide derived from the pre-S1 domain of the HBV large envelope protein. The molecule binds to the sodium taurocholate cotransporting polypeptide (NTCP) — the entry receptor that HDV and HBV both use to enter hepatocytes — and blocks viral entry as a first-in-class entry inhibitor. The Phase 3 MYR301 trial documented a statistically significant combined virologic and biochemical response at week 48 versus delayed-treatment control, supporting the accelerated-approval threshold. Continued approval depends on confirmatory trial verification of clinical benefit. Bulevirtide has been EU-approved under conditional marketing authorization since 2020. Gilead shares closed Friday at $134.36, up roughly 3%.

Research · View digest

Hepcludex Mechanism Deep-Dive: Why a Lipopeptide Entry Inhibitor Cures What Antivirals Couldn't — NTCP Receptor Biology and the HBV/HDV Dependency

Bulevirtide's mechanism reveals why an entry inhibitor succeeded where small-molecule antivirals didn't. HDV is an obligate parasite of HBV — the delta virus uses the HBV envelope to assemble its virions and the HBV-derived large surface protein to enter hepatocytes via the sodium taurocholate cotransporting polypeptide (NTCP) receptor on hepatocyte cell membranes. Existing HBV antiviral nucleoside/nucleotide analogs (entecavir, tenofovir) suppress HBV replication but don't clear circulating HBsAg or interrupt the HDV entry cycle. Bulevirtide's 47-amino acid sequence — derived from the HBV pre-S1 domain — binds NTCP competitively and blocks both HDV and HBV entry. Real-world EU experience since 2020 shows roughly 50-60% of HDV patients achieve undetectable HDV RNA after 96 weeks of treatment, with a favorable safety profile dominated by injection-site reactions. The US approval expands access for an estimated 75,000-100,000 US patients with chronic HDV, most of whom were previously treated empirically with off-label interferon alfa with poor tolerability.