A two-target immune drug did not clearly beat dummy injections in a painful skin disease

PAINFUL LUMPS form deep in the skin, usually where skin touches skin, in the armpits, groin, inner thighs, buttocks and under the breasts. They often look like boils that keep coming back. Untreated, they can become pockets of pus that break open and scar, and pus-filled tunnels can form under the skin. Scarring can make sitting, walking or reaching hard, and many people live with the condition for years before anyone names it. It is not acne, not contagious, not a sexually transmitted infection and not caused by unclean skin. It cannot be cured, but treatment can help prevent new lumps and ease the pain. Its name is hidradenitis suppurativa, also called acne inversa, or HS.

The body uses chemical signals to drive inflammation. One of them is interleukin-17, or IL-17. Another, B-cell activating factor, or BAFF, helps a class of immune cells called B cells survive. Zura Bio has a two-headed antibody that it says is designed to neutralize IL-17 and BAFF at once. It was made by joining an antibody called tabalumab with a fragment of another, ixekizumab. Before Zura licensed tibulizumab (ZB-106), Lilly had given it to people in early studies in Sjögren's syndrome and rheumatoid arthritis.

For a mid-stage test in HS, Zura assigned 247 adults with moderate-to-severe disease by chance to one of two doses, 300 mg or 150 mg, or to dummy injections, all given as shots under the skin. Neither they nor the people scoring their skin were told who had received what. The main question, set in advance, was whether the drug shrank the number of abscesses and inflamed lumps after 16 weeks by more than the dummy injections did. The company calls the trial TibuSHIELD, double-blind and placebo-controlled. That pre-set test is the primary endpoint, and the tally is the AN count.

In results released on November 9th, the AN count fell by 56.0% on the higher dose and 58.1% on the lower one, against 52.5% on placebo, with 82 people per group. Neither dose met the endpoint. A common bar for a patient's response is a fall of at least half in the AN count with no rise in abscesses or in draining tunnels, the channels that leak pus. That bar is HiSCR50, and a fall of three-quarters is HiSCR75. HiSCR50 rates were 48.0% and 52.7% on the two doses and 45.5% on placebo, and HiSCR75 rates were 35.3%, 34.0% and 28.1%, so those tests were missed too. Both were estimated with a statistical method for missing data, so they are not headcounts.

Sandeep Kulkarni, MD, Zura's chief executive, said the results "highlight the challenges of developing medicines in hidradenitis suppurativa, including the high variability of placebo responses." An antibody that blocks IL-17 signals, UCB's bimekizumab (Bimzelx), was approved by America's Food and Drug Administration for HS in November 2024. Its label reports week-16 HiSCR50 rates of 48% and 52% on the drug in two large trials, against 29% and 32% on placebo. As a cross-trial observation, not a head-to-head test, the drug rates resemble TibuSHIELD's and the placebo rates are far lower.

By week 16, 43 of 82 people on each dose had a new medical problem of some kind, against 38 of 82 on placebo, and one person on the higher dose died of cardiac arrest, which the site investigator judged unrelated to treatment.

Volunteers could then join an optional further 16 weeks in which everyone received the drug. Such an open-label extension can show whether side effects build up and improvement lasts, but with no comparison group it cannot show that the drug caused any improvement. The registry lists the study as active but not recruiting, with completion expected in April 2027, and Zura has not said whether those still taking part will finish. The update is a company announcement, not a peer-reviewed paper, and gave no results for pain or quality of life, which the registry planned to measure. One trial of 247 adults cannot show that the drug helps or fails every person with HS, or that blocking IL-17 and BAFF together is a bad idea in other diseases.

People with HS still have the treatments they had before, bimekizumab among them. After sixteen weeks, people given dummy injections had improved almost as much as those given a drug designed to block two immune signals at once. Zura is therefore stopping work on tibulizumab in HS, though it will keep testing it in systemic sclerosis and in a planned trial in polymyalgia rheumatica.