Q&A: Tulisokibart Results and TL1A Inhibition in HS, With Alexa Kimball, MD, MPH

Tulisokibart, an investigational monoclonal antibody targeting tumor necrosis factor-like ligand 1A (TL1A), outperformed placebo on lesion response at week 16 in the phase 2b MK-7240-012 trial (NCT06956235) in adults with moderate to severe hidradenitis suppurativa (HS). Merck reported the results as a late-breaking abstract at the 2026 European Academy of Dermatology and Venereology (EADV) Congress in Vienna, Austria.¹

“Results from the MK-7240-012 trial are promising,” said Alexa B. Kimball, MD, MPH, professor of dermatology at Harvard Medical School, president and CEO of Harvard Medical Faculty Physicians at Beth Israel Deaconess Medical Center, and lead investigator of the trial.¹

During the randomized, double-blind study, Kimball et al assigned 149 individuals to be treated with tulisokibart 480 mg every 2 weeks (n = 42), 480 mg every 4 weeks (n = 42), 240 mg every 4 weeks (n = 21), or placebo (n = 44), with a Bayesian primary analysis incorporating historical placebo data.¹ At week 16, HiSCR50 response attained 72% and 64% with the 2 higher doses vs 35% with placebo, meeting the team’s main end point. The low dose, evaluated by the investigators as an exploratory arm, saw HiSCR50 among 52%.

HiSCR75 rates followed a dose-dependent pattern at 41%, 40%, and 29% across the high, medium, and low doses, compared with 15% for placebo.¹ The high dose also produced the largest gain in Dermatology Life Quality Index (DLQI), with a mean change of -5.62 vs -2.46 with placebo.²

TL1A inhibition represents a mechanism distinct from the tumor necrosis factor and interleukin-17 pathways targeted by HS biologics approved to date, and tulisokibart is also in phase 3 development for ulcerative colitis and Crohn’s disease.¹ In the following interview, Kimball spoke with HCPLive at EADV 2026 in Vienna about the standout efficacy findings and the biologic rationale for targeting TL1A in HS:

HCPLive: What were the key takeaways from the phase 2b MK-7240-012 trial of tulisokibart in HS, and which efficacy findings stood out most?

Alexa Kimball, MD, MPH: First, HS has been on an incredible journey of exciting developments in terms of how we manage our patients, with really improving efficacy and safety over the past decade. It’s been amazing. This latest set of data for tulisokibart in this phase 2 program continues to show that we can reach high levels of efficacy. We were very excited because this is a new mechanism of action in the world of dermatology, which is TL1A inhibition. What we saw in this program was that, in this 3-arm dosing regimen vs placebo, HiSCR50 and HiSCR75 at week 16 showed very strong results, in the highest tier of efficacy results that we have seen to date.

HCPLive: What is the biologic rationale for targeting TL1A in HS, and how might this mechanism differ from TNF and IL-17 inhibitors?

Alexa Kimball, MD, MPH: Many people will be familiar with the use of TNF inhibitors throughout dermatology, and certainly for HS, that’s where we really started our efficacy and therapeutic journey for our patients. TL1A is actually a related cytokine to TNF. It’s in the TNF superfamily of cytokines, but it works through a different mechanism. More precisely, it’s a co-stimulatory molecule, and we were investigating a lot of co-stimulatory molecules even 20 years ago to try to break the cycle of inflammatory activation as cells talk to each other to get that cascade going.

You need a number of different things to happen. The way to think about it is like a docking mechanism. There are multiple pieces in the dock that come together to get that activity, and this is one of them. If you don’t have that docked, you have a wobbly interaction.

What’s interesting about TL1A, though, is that it interacts with something called DR3, or death receptor 3, which makes you wonder what death receptor 1 is. In any event, DR3 is found on a lot of different types of inflammatory cells, so in some ways, it has a very broad impact. What we’re trying to figure out is how this translates into the therapeutic benefits we see.

One other interesting element of the TL1A pathway is that it may have an antifibrotic effect. HS is a disease with a lot of scarring, so that would certainly be a substantial benefit to our patients if that part of the mechanism of action pans out in a way that is helpful in how scars develop and remodel over time.

Editor’s Note: This transcript has been edited for grammar and clarity using artificial intelligence tools. Kimball has disclosed her work a paid consultant for Merck.

References

1. Merck. Merck’s tulisokibart met primary and key secondary endpoints in phase 2b study in patients with moderate to severe hidradenitis suppurativa (HS). Published September 30, 2026. Accessed November 3, 2026. https://s2.q4cdn.com/584635680/files/doc_news/Mercks-Tulisokibart-Met-Primary-and-Key-Secondary-Endpoints-in-Phase-2b-Study-in-Patients-With-Moderate-to-Severe-Hidradenitis-Suppur-QPD75.pdf.

2. Smith T. Tulisokibart shows phase 2b efficacy in moderate to severe HS. HCPLive. Published September 30, 2026. Accessed November 3, 2026. https://www.hcplive.com/view/tulisokibart-phase-2b-efficacy-moderate-severe-hs.