GSK Discontinues HSV Vaccine After Failed Phase I/II Trial

In September 2024, GlaxoSmithKline (GSK) announced it was discontinuing its investigational herpes simplex virus vaccine candidate, GSK3943104, after it failed to meet its primary efficacy objectives in a proof-of-concept study. The decision means GSK will not advance the candidate to Phase III trials, and the company currently has no other HSV vaccine in its pipeline.

What Happened in the Trial

The TH HSV REC-003 trial was a randomized, observer-blinded study involving 342 participants split into two groups: healthy volunteers aged 18 to 40 and patients aged 18 to 60 with recurrent genital herpes.

GSK reported no safety concerns with the candidate, but the vaccine did not reduce the frequency or severity of HSV-2 outbreaks to a meaningful degree.

Primary endpoints included local reactions at the injection site and systemic effects such as fever and fatigue — the vaccine cleared those bars but failed on efficacy, which is what ultimately matters for approval.

What This Means for HSV Vaccine Research

Developing an effective herpes vaccine has proven consistently difficult.

The virus has evolved mechanisms to evade immune surveillance, establishing lifelong latency in nerve cells in a way that the immune responses generated by current vaccine designs have not been able to overcome.

GSK's setback is the latest in a long series of failed or stalled candidates going back decades.GSK said it would continue collecting follow-up safety data from the trial and that the findings could still inform future research directions.

But for now, the company has stepped back entirely from the herpes vaccine space.

Who Is Still Working on an HSV Vaccine?

Several companies are continuing to pursue HSV vaccines, with mRNA technology attracting the most interest following its success in COVID-19 vaccines.

Moderna has been advancing mRNA-1608, a therapeutic candidate targeting HSV-2 that aims to reduce outbreaks in already-infected individuals rather than prevent initial infection.

BioNTech entered Phase I trials with its own HSV candidate, BNT163, in late 2022.

Other programs at smaller biotechs are also in early development, some targeting the viral glycoproteins that help HSV evade the immune system.A therapeutic vaccine that reduces outbreak frequency and transmission risk in people who already carry HSV would represent a major step forward even if it falls short of being a true cure.

Given how many hundreds of millions of people carry HSV, even modest efficacy at scale could have a large public health impact.

The Bigger Picture

GSK's exit is a setback but not a signal that progress has stopped. The field has gained better tools, including structural biology advances that reveal how HSV evades immunity, and the mRNA platform gives researchers more flexibility to iterate quickly on vaccine design. The hope is that lessons from each failed trial get incorporated into the next generation of candidates rather than being lost.