GSK bepirovirsen

Chronic hepatitis B · NDA

Of 100 applications in this same position, about 94 get approved.

Until the FDA deadline21d

Base rate95%

Gap−1pts

PDUFA target date 2026-10-26the FDA may act earlier or later

Summary

We put approval of GSK's bepirovirsen for chronic hepatitis B at 94%, in line with the ~95% base rate for big-pharma applications. GSK is the sponsor; Ionis is the licensor. Two replicate Phase 3 trials (B-Well 1/2, about 1,800 patients) met their primary endpoint on the field's preferred endpoint: functional cure in 19% versus 0% on placebo. The drug has Breakthrough designation and priority review, and no advisory committee has been called. Remaining risks: ALT flares in about a quarter of patients, reversible platelet and kidney-function drops that will need monitoring, and manufacturing sites we cannot see. Confidence is high.

Recorded 2026-10-04 19:57 UTC · v1Proof ↓

Evidence · 6 items

Why it stays close to 95%

Indication

Chronic hepatitis B in adults; 6-month finite subcutaneous antisense oligonucleotide course aimed at functional cure (Phase 3 B-Well 1/2 population: nucleos(t)ide-analogue-treated, baseline HBsAg <=3000 IU/mL)

95% of comparable applications were approved in the past: the opponent every forecast has to beat. Below are the reasons this forecast stays close to it.

▲ supports approval, ▼ counts against it. More squares, more weight.

01▲ SupportsSmall Big-pharma sponsor and original NDA, not a resubmission

GSK, not Ionis, is the NDA holder and runs all regulatory work. Drugs@FDA shows no prior action on bepirovirsen. The right anchor is the big-pharma base rate (about 95%), not the 76% small/mid-company rate.

Source: Ionis 10-Q filed 2026-07-29 (GSK responsible for all global development and regulatory activity); GSK press release 2026-04-28
02▲ SupportsSmall Two replicate, placebo-controlled Phase 3 trials met their primary endpoint with a very large contrast, on an endpoint regulators have endorsed

In the pooled B-Well 1/2 data (about 1,830 patients), functional cure reached 19% on bepirovirsen (233/1,220) versus 0% on placebo (0/614), p<0.001. Each trial was positive on its own (20% and 19%). In the HBsAg <=1000 IU/mL stratum, the key secondary endpoint, the rate was 26% (200/768) versus 0/393. Results were published in NEJM. Functional cure (sustained HBsAg loss with HBV DNA <LLOQ 24 weeks off treatment) is the preferred primary endpoint in the 2022 AASLD-EASL treatment-endpoints guidance, which was written with regulators taking part. The step is small only because the base rate already assumes a clean package.

Source: GSK EASL 2026 press release (via NATAP); BioPharma Dive 2026-05-28; J Hepatol 2023 AASLD-EASL endpoints report
03▲ SupportsSmall Breakthrough Therapy designation, Fast Track and Priority Review

The FDA granted BTD when it accepted the NDA for priority review, with an FDA-assigned PDUFA date of 26 October 2026. GSK's Q2 report (28 July 2026) says the review is ongoing and that a decision is expected by that date. No problems have been disclosed.

Source: GSK press release 2026-04-28; GSK 6-K Q2 2026 results filed 2026-07-28
04▼ AgainstSmall Safety burden typical of antisense oligonucleotides: hepatic flares, platelet and kidney-function drops

During treatment, ALT rose to >=3x ULN in 24% of patients and to grade 3 in 6%. These rises are read as immune-mediated clearance flares. Platelet counts and eGFR fell in a reversible, treatment-dependent way. Injection-site reactions were the most common adverse event. Grade 3 AEs occurred in 16%, and trial monitoring was every 1-2 weeks. This points to warnings and monitoring requirements in the label, or possibly a REMS, more than to a CRL. No deaths or discontinuation signals were reported.

Source: ACG Evidence-Based GI review, August 2026 (gi.org); BioPharma Dive 2026-05-28
05▼ AgainstSmall First-in-class antisense drug for an infectious disease, made by contract manufacturers we cannot see

Oligonucleotide synthesis is mature, and GSK has a strong record. Public sources do not name the drug-substance or fill-finish sites, so inspection risk cannot be checked directly. No 483s or warning letters have been linked to this product.

Source: No public manufacturing disclosure found; GSK and Ionis filings as of 2026-10-04
06▲ SupportsSmall No advisory committee about three weeks before the PDUFA date

No Antimicrobial Drugs Advisory Committee meeting is listed for bepirovirsen. The only human-drug AdComs announced for October 2026 concern other products. This fits a review the FDA considers routine.

Source: FDA advisory committee calendar / search, 2026-10-04

What would change this forecast

01
GSK discloses a CRL, a major amendment (a 3-month extension would only move the date), or a facility inspection problem
02
The FDA asks for a REMS or more safety data on hepatic flares, thrombocytopenia or renal effects late in the review
03
Reports of FDA staffing disruption that cause a missed goal date (that would delay the resolution, not count as NO)

Any change is published as a new version; earlier versions stay exactly as they were.

Confidence

High

Manufacturing and inspection risk

Low

This is a synthetic oligonucleotide made by an experienced big-pharma sponsor, and no inspection problems have been disclosed. The sites are not public, so the residual risk is unknown rather than zero. Big-pharma CRLs in 2024-26 were mostly about facilities, which is the main route to a NO here.

Record · version 1

Written on 2026-10-04, 22 days before the PDUFA target date.

Timeline

Versions

v1 2026-10-04 19:57 UTC 94% Current version JSON ↓.ots ↓ ○ Timestamp submitted, awaiting block confirmation

Fingerprint

SHA-25650fc299752211411f6cbbe2626ab9e32556b4b54b5ac4018806f0718d4344368

The fingerprint of the v1 file. It is what the timestamp commits to: change one character of the file and the fingerprint no longer matches.

Verify it yourself

Download the JSON file above and the .ots file of the same name into one folder.
Compute the SHA-256 of the file. It should match the fingerprint above.
Verify with OpenTimestamps. Once the timestamp is in a Bitcoin block, ots verify reports the block time if you run a Bitcoin node; without one, drop both files on the verifier at opentimestamps.org, or run ots info to see the block height and look it up in any block explorer. If the block time is before the FDA’s decision, the file cannot have been written afterwards.

pip install opentimestamps-client
shasum -a 256 v1_20261004T195758Z.json
ots verify v1_20261004T195758Z.json.ots
ots info v1_20261004T195758Z.json.ots

Scoring rule

What is scored is the last version recorded at least 2 days before the PDUFA target date; if the FDA decides early, only versions recorded before the day of its decision count. For this forecast the cutoff is 2026-10-24. Its error (also called the Brier score) is the squared distance between the forecast and the outcome, set against the error of quoting the base rate only.