T-Cell Rebalancing Therapy Active in Previously Treated Atopic Dermatitis

ORLANDO — A novel therapy for atopic dermatitis (AD) led to at least 75% improvement in a third of patients after 6 months, a placebo-controlled trial showed.

Including patients who used topical rescue medication, almost half of patients treated with rocatinlimab met the 75% response criteria compared with 16% of placebo-treated patients. Additionally, a fifth of patients met the co-primary endpoint of clear/nearly clear skin by the validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) score, increasing to one-fourth when topical rescue medication was included, compared with less than 7% of the placebo group.

An OX40 receptor (OX40R) inhibitor, rocatinlimab reduced concentrations of pathogenic OX40R-positive T cells but not conventional T cells.

Treatment-emergent adverse events (TEAEs) occurred in a similar proportion of patients in each group, and were mostly mild or moderate in severity, reported Emma Guttman-Yassky, MD, PhD, of the Icahn School of Medicine at Mount Sinai in New York City, at the American Academy of Dermatology annual meeting.

“The ROCKET-Horizon trial met the co-primary and key secondary endpoints in a highly diverse, treatment-experienced, moderate-to-severe atopic dermatitis patient population,” said Guttman-Yassky. “Even higher efficacy was observed with rocatinlimab versus placebo when allowed to bridge with rescue therapy. Rocatinlimab efficacy did not plateau at week 24, suggesting potential for additional efficacy beyond the 24-week trial period.”

“The proposed mechanism of action of rocatinlimab, as a first-in-class T-cell rebalancing therapy, is supported by specific reduction of OX40R-positive T cells while maintaining conventional T cells,” she added. “The ongoing ROCKET program will further substantiate rocatinlimab’s clinical profile by assessing disease control and deepening response beyond week 24.”

During a discussion that followed her presentation, Guttman-Yassky was asked about the role of OX40 in other diseases. In early studies, she compared OX40 expression in AD and psoriasis and found that the molecule was highly expressed in the former, and was correlated with disease severity, but not in the latter. Moreover, a clinical trial of the drug in psoriasis subsequently “failed miserably.”

The drug could have a role in other inflammatory conditions, including asthma, she noted.

In response to another question, Guttman-Yassky said the analysis of the primary endpoints occurred at 24 weeks because the investigators believe the drug’s maximum efficacy will be reached later, as compared with drugs that reach maximum efficacy at 12 or 16 weeks.

“I think it may be possible to stop the drug and then restart it or to give it much less often,” she said.

OX40R is a co-stimulatory molecule expressed on activated effector and memory T cells, and OX40R-positive T cells release pro-inflammatory cytokines that drive memory responses in AD. The number and activity of OX40R-positive T cells increase in AD, leading to T-cell imbalances. Rocatinlimab inhibits and reduces pathogenic T cells by targeting OX40R, leaving fewer pathogenic T cells to drive inflammation and disease activity.

Guttman-Yassky reported primary results from the phase III ROCKET-Horizon trial, one of eight trials in a clinical research program that will provide a “holistic view” of rocatinlimab’s profile for up to 104 weeks of follow-up. The investigators randomized patients 3:1 to rocatinlimab or placebo, with each arm beginning with two loading doses followed by dosing every 4 weeks. The primary endpoints were a vIGA-AD score of 0 or 1 with ≥2-point reduction from baseline and an Eczema Area and Severity Index score ≥75 (EASI-75), both assessed at 24 weeks.

Rescue medication was allowed from day 1, said Guttman-Yassky. For the primary analysis, patients who required rescue medication were considered non-responders, regardless of response status. A prespecified analysis included patients who received topical rescue medication. Rocatinlimab was discontinued if a patient required systemic rescue medication.

The primary analysis included 728 patients who had a mean age at AD onset of 13.6 and a mean AD duration of 24.8 years. More than 60% had received systemic therapy, 22% had received biologic therapy, and 66% had type 2 comorbidities.

During the trial, a third of patients in the rocatinlimab group received rescue medication, which was limited to topical treatment in 28.7%. Rates of any rescue therapy and topical rescue therapy were 41.5% and 29.5% in the placebo group, respectively. Guttman-Yassky noted that 4.8% of patients in the rocatinlimab arm received systemic rescue medication versus 12% in the placebo group.

At 24 weeks, 32.8% of the rocatinlimab group and 13.7% of the placebo group had EASI-75 responses (P<0.001). The rates of vIGA-AD 0/1 scores were 19.3% with rocatinlimab and 6.6% with placebo (P<0.001). Analyses that included topical rescue medication showed EASI-75 rates of 46.6% versus 15.8% and vIGA-AD 0/1 rates of 24.1% versus 6.6% (P<0.001).

Four times as many patients in the rocatinlimab arm met EASI-90 response criteria (19.9% vs 4.9%), increasing to almost five times as many with rescue medication (26.3% vs 5.5%). Additionally, 24% of patients in the rocatinlimab arm had at least a 4-point reduction in worst pruritus score compared with 10.5% of placebo patients, increasing to 32.9% versus 18.5% with rescue medication.

The most common TEAEs were dermatitis (19.1% with rocatinlimab vs 26.7% with placebo), pyrexia (10.3% vs 1.1%), nasopharyngitis (8.8% vs 11.7%), and headache (7.2% vs 3.9%). Fewer than 3% of patients discontinued assigned treatment in each group.

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