Merck's Tulisokibart Becomes First Anti-TL1A Antibody to Hit Phase 3 Remission Endpoint in Ulcerative Colitis
Merck says its TL1A antibody tulisokibart met the primary and key secondary endpoints in the Phase 3 ATLAS-UC induction study, a first for the drug class.
Overview
Merck has reported that its experimental antibody tulisokibart met the primary endpoint and key secondary endpoints in a pivotal Phase 3 study in moderately to severely active ulcerative colitis, results the company describes as the first positive Phase 3 induction data for any drug aimed at the TL1A target. According to Merck, the ATLAS-UC induction-only study showed that tulisokibart, an investigational humanized monoclonal antibody directed to TL1A, achieved clinical remission according to the Modified Mayo Score (MMS) at week 12.
What We Know
Tulisokibart, also known by the code MK-7240, is an investigational humanized monoclonal antibody directed to tumor necrosis factor-like cytokine 1A, or TL1A, a target Merck calls novel, according to Merck. The same release states that the trial’s primary endpoint was clinical remission according to the Modified Mayo Score at week 12, an endpoint corroborated by Clinical Trials Arena.
The ATLAS-UC program consists of two independent studies, according to Merck: Study 1, which includes both induction and maintenance treatment, and Study 2, which includes only induction treatment. The newly reported data come from the induction-only study, which Clinical Trials Arena identifies as NCT06052059, alongside the ongoing induction and maintenance study registered as NCT06651281. Participants were randomized to receive a high dose of intravenous tulisokibart, a low dose of intravenous tulisokibart, or an intravenous placebo, Merck said.
Beyond the primary endpoint, the study met key secondary endpoints measuring the percentage of patients who experienced endoscopic improvement, achieved clinical response per the Modified Mayo Score, and demonstrated histologic-endoscopic mucosal improvement, according to Merck. The company added that no safety concerns were identified, consistent with previously reported Phase 2 studies.
Merck framed the result as a first for the drug class. “These positive Phase 3 induction results for tulisokibart are the first for an anti-TL1A biologic,” said Dr. Eliav Barr, senior vice president, head of global clinical development and chief medical officer, Merck Research Laboratories, according to Merck. The release states that tulisokibart is the first anti-TL1A monoclonal antibody to demonstrate clinical remission at 12 weeks in moderately to severely active ulcerative colitis in a Phase 3 trial.
Ulcerative colitis is described by Merck as a chronic progressive immuno-fibrotic disease that affects the large intestine and rectum, with symptoms including diarrhea, rectal bleeding, abdominal pain, bowel urgency and weight loss. Merck says millions of people worldwide live with the condition.
The drug reached Merck through its acquisition of Prometheus Biosciences, where the antibody was known as PRA023. According to Merck, the company agreed to buy Prometheus for $200.00 per share, an equity value of approximately $10.8 billion, in a deal announced April 16, 2023. The earlier release describes PRA023 as a humanized monoclonal antibody that binds both soluble and membrane-associated human TL1A with high affinity and specificity. Clinical Trials Arena similarly reports the $10.8bn purchase at $200 a share in April 2023.
The Phase 3 readout follows earlier mid-stage data. In the Phase 2 ARTEMIS-UC trial, patients treated with tulisokibart showed a higher rate of remission than those on placebo, 26 percent versus 1 percent respectively, according to EMJ, which reports that the trial’s Cohort 1 included 135 patients and that the primary endpoint was clinical remission at week 12. EMJ describes the Phase 2 dosing as intravenous tulisokibart at 1,000 mg on Day 1, then 500 mg at weeks 2, 6, and 10, and notes that a second cohort focused solely on patients with a positive test for likelihood of response.
What We Don’t Know
Merck’s announcement is a topline disclosure. The company has not released the magnitude of the remission difference between tulisokibart and placebo in the Phase 3 study, nor the breakdown between the high-dose and low-dose arms. Merck said the ATLAS-UC Study 2 results will be presented together with results from the ongoing induction and maintenance study, Study 1, at an upcoming scientific congress, and will be shared with regulatory authorities. The data from the longer maintenance study, which will indicate how durable the benefit is, are still pending.
Analysis
TL1A has become one of the most closely watched targets in inflammatory bowel disease, drawing several large pharmaceutical companies into the field. According to pharmaphorum, Roche entered the category with afimkibart, which stemmed from its $7.1 billion purchase of Telavant, while Sanofi licensed rights to Teva’s duvakitug in a deal valued at around $1.5 billion. A separate pharmaphorum report lists Spyre Therapeutics’ SPY002 among the Phase 2 contenders and notes analyst projections of $4 to $5 billion in peak sales for tulisokibart.
Merck is pursuing the antibody across a broad set of conditions. According to pharmaphorum, tulisokibart is already in Phase 3 testing for ulcerative colitis and Crohn’s disease, and the company has started a trio of new Phase 2b studies in rheumatoid arthritis, ankylosing spondylitis, and hidradenitis suppurativa. Clinical Trials Arena lists additional indications under study, including psoriatic arthritis and systemic sclerosis-associated interstitial lung disease, underscoring the scope of the program Merck inherited from the Prometheus deal.