Tulisokibart Phase 2b HS Signal Is Large but One Phase Away From Proof

Merck's Tulisokibart Achieves Positive Phase 2b Results in HS

Merck announced positive results from its Phase 2b MK-7240-012 trial evaluating tulisokibart, an investigational anti-TL1A monoclonal antibody, in patients with moderate to severe hidradenitis suppurativa (HS). The study successfully met its primary endpoint, Hidradenitis Suppurativa Clinical Response 50 (HiSCR50) at week 16, with 72% of high-dose (480 mg Q2W) and 64% of medium-dose (480 mg Q4W) patients achieving the response, significantly outperforming the 35% seen in the placebo group. Key secondary endpoints, including HiSCR75 and improvements in the Dermatology Life Quality Index (DLQI), also showed numerical improvements. Tulisokibart demonstrated a safety profile comparable to placebo, with infrequent serious adverse events, supporting its advancement to Phase 3 for HS.

• Tulisokibart demonstrated significant efficacy in achieving the primary endpoint, HiSCR50, at week 16. The high-dose group (480 mg Q2W) showed a 72% response rate, and the medium-dose group (480 mg Q4W) achieved 64%, representing substantial improvements of 37% and 29% respectively over the 35% response rate observed in the placebo group.
• Beyond the primary endpoint, tulisokibart also showed favorable numerical improvements in key secondary endpoints. HiSCR75 was achieved by 41% of high-dose and 40% of medium-dose patients, compared to 15% in the placebo group. Additionally, the high-dose cohort experienced a mean reduction of -5.62 in the Dermatology Life Quality Index (DLQI), indicating a 3.16-point improvement over placebo.
• The safety profile of tulisokibart was comparable to placebo across all treatment groups. Adverse events occurred in 42.9% (high-dose), 47.6% (medium-dose), and 52.4% (low-dose) of participants, versus 40.9% in the placebo group. Serious adverse events were infrequent and occurred at similar rates (2.4% in high- and medium-dose, 4.8% in low-dose, and 2.3% with placebo), with no serious or opportunistic infections reported.

The Persistent Challenges in Treating Moderate to Severe HS

Despite advances in both medical and surgical management, hidradenitis suppurativa (HS) remains a therapeutically complex disease with high rates of recurrence and significant unmet need. Multiple intersecting challenges — spanning antibiotic resistance, outcome measure validity, surgical limitations, and clinical trial methodology — continue to impede optimal patient care.

• Antibiotic resistance is a growing and documented concern. Patients using topical clindamycin were more likely to grow clindamycin-resistant Staphylococcus aureus compared with patients using no antibiotics (63% vs 17%; P = .03). Patients taking ciprofloxacin were more likely to grow ciprofloxacin-resistant methicillin-resistant S. aureus compared with patients using no antibiotics (100% vs 10%; P = .045). Separately, bacterial cultures from HS lesions have demonstrated resistance prevalence rates of 65.7% for clindamycin, 69.3% for rifampicin, 74% for ciprofloxacin, 84.7% for tetracycline, and 89.0% for erythromycin — antibiotics that are cited as empiric choices in HS therapeutic guidelines.

• Validated outcome measure instruments are largely absent from HS clinical trials. A systematic review of 12 randomised controlled trials identified 30 outcome measure instruments in use, of which 27 (90%) lacked any validation data. Where validation evidence exists, issues of low methodological quality or incomplete validity assessment persist, meaning no instruments can be fully recommended. The HiSCR instrument, while supported by good-quality validation data, has gaps including absence of assessment of internal consistency, inter-rater reliability, and minimal clinically important difference, and convergent validity fell below the acceptable range for some comparisons.

• The HiSCR's lack of dynamic tunnel measurement limits its utility as a primary endpoint. Newer instruments such as the dichotomous IHS4 and HASI-R have been developed with adequate validation data as contenders for primary outcome measures in HS trials, and patient-reported outcomes are being developed through the HISTORIC collaboration. Consensus on consistent administration and interpretation of pain measurement instruments also remains outstanding.

• "Data wobble" in HS randomised controlled trials introduces methodological uncertainty. A retrospective review of 21 HS clinical trials identified that HiSCR wobble — an unexpected decline in efficacy between the penultimate visit and the prespecified primary endpoint week — occurred significantly more often in RCT study drug arms compared to open-label arms (40.7% vs 0%). RCT arms with HiSCR wobble had lower baseline draining fistula counts (2.3 vs 3.2) and numerically fewer Hurley stage 3 patients (33.2% vs 42.5%), suggesting that a higher proportion of less severe patients at baseline and a greater proportion of female patients may be contributing factors.

• Surgical approaches carry meaningful recurrence rates, particularly by anatomical location. The standard deroofing technique showed a recurrence rate of 17% after a median of 4.6 months across 88 lesions. A modified deroofing approach incorporating meticulous sinus tract excision reduced recurrence to 14% overall, but recurrence varied substantially by site — 6% in the axillary region versus 25% in the inguinal region — indicating that surgical outcomes remain anatomically dependent. Postoperative bleeding occurred in 7% of treated locations with the modified approach.

• High rates of disease recurrence and progression persist despite the availability of multiple therapeutic options, including topical antibiotics, systemic antibiotics, biologics, deroofing, local excision, and wide local excision. The integration of biologic therapy and surgery has generated interest, with perioperative adalimumab associated with greater response rates and improved inflammatory load and pain without increased postoperative infectious complications, though several practical aspects of combined therapy remain poorly defined.

Tulisokibart's Promising Efficacy and Safety in HS Phase 2b

The RELIEVE multicenter randomized controlled trial evaluated LAight® therapy — a combination of intense pulsed light and radiofrequency — as an adjunct to topical clindamycin 1% solution in patients with Hurley stage I and II hidradenitis suppurativa. Over 16 weeks, the combination arm achieved a mean ΔIHS4 of -7.2 ± 6.7 (-60.0%), compared with -1.8 ± 5.6 (-17.8%) in the clindamycin monotherapy arm (p < 0.001). Secondary endpoints — including DLQI, HiSCR, Pain-NRS, and HADS — consistently favored the combination, and all reported side effects were mild and transitory.

The BE HEARD I&II phase 3 randomized controlled trials, along with their open-label extension BE HEARD Extension, assessed bimekizumab — a humanized IgG1 monoclonal antibody selectively inhibiting IL-17A and IL-17F — in patients with moderate to severe HS over up to 2 years. At Year 2, 85.4%, 77.1%, 57.6%, and 44.2% of patients achieved HiSCR50, HiSCR75, HiSCR90, and HiSCR100, respectively. Treatment-emergent adverse events did not increase with longer exposure (Year 1: 261.6/100 PY; Year 2: 235.7/100 PY), with the most common Year 2 TEAEs being hidradenitis (26.6/100 PY), coronavirus infection (23.1/100 PY), and oral candidiasis (12.5/100 PY). Bimekizumab also demonstrated rapid reductions in skin pain from Week 2, with improvements in HRQoL — measured by HiSQOL and DLQI — sustained through Week 48 and beyond, and no new safety signals identified with longer exposure.

A 48-week real-world prospective trial conducted in Korea evaluated secukinumab — an IL-17A inhibitor administered at 300 mg subcutaneously — in 10 patients with moderate-to-severe HS. At Week 48, 90% of patients achieved HiSCR, 90% met the IHS4-55 threshold, and 60% reached the NRS30 pain reduction criterion. Patients with Hurley stage II disease, treatment delays of fewer than 10 years, or no prior biologic exposure demonstrated faster initial responses, though response rates equalized by Week 48. The majority of patients either discontinued or transitioned to monotherapy with systemic antibiotics, underscoring a meaningful reduction in concomitant antibiotic use.

Tulisokibart's Broad Development Program and Immuno-Fibrosis Approach

Tulisokibart, an anti-TL1A monoclonal antibody, is under active clinical investigation across several inflammatory indications beyond hidradenitis suppurativa, reflecting the broad pathological role of the TL1A/DR3 axis in driving both immune activation and fibrosis. Its development spans gastrointestinal and airway diseases, with phase 2 and phase 3 programs underway. The dosing regimen used across trials has been intravenous administration (1000 mg on day 1 and 500 mg at weeks 2, 6, and 10).

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Tulisokibart's Strong Phase 2b Data: A New Hope for HS

Hidradenitis suppurativa (HS) remains a profoundly challenging and debilitating chronic inflammatory skin disease, significantly impacting patients' lives despite the availability of approved treatments like anti-TNF-α (adalimumab) and anti-IL-17A (secukinumab) biologics. Many individuals still struggle to achieve adequate disease control or experience intolerance to existing therapies, highlighting a persistent unmet medical need.

The recent positive Phase 2b results for Merck's investigational anti-TL1A monoclonal antibody, tulisokibart, represent a significant development in this landscape. Achieving a HiSCR50 in 72% of high-dose patients and 64% of medium-dose patients, markedly superior to the 35% seen with placebo, demonstrates robust efficacy. This strong performance, coupled with a safety profile comparable to placebo and infrequent serious adverse events, positions tulisokibart as a promising new therapeutic candidate.

This outcome carries several strategic implications. Firstly, it validates the anti-TL1A pathway as a potentially effective target for HS, de-risking future development in this and potentially other inflammatory conditions. Secondly, with its novel mechanism, tulisokibart could offer a distinct treatment option, particularly for patients who have not responded to or cannot tolerate current standards of care. However, the path forward is not without considerations. The impressive Phase 2b results must be replicated in larger, longer-duration Phase 3 trials to confirm efficacy and safety across a broader patient population. Furthermore, while its efficacy against placebo is clear, the absence of direct head-to-head comparative data against established biologics means that market differentiation will rely heavily on its unique mechanism and potentially its profile in specific patient subgroups. Finally, the long-term safety and durability of response, crucial for a chronic condition, will need to be thoroughly evaluated in subsequent studies. Nevertheless, these data suggest tulisokibart could significantly expand the therapeutic arsenal for HS, offering renewed hope for patients and clinicians alike.