麻豆传媒

More than a third of patients with plaque psoriasis had complete or near-complete clearance with a first-in-class nonsteroidal topical therapy, results of two randomized trials showed.

Once-daily application of tapinarof, an aryl hydrocarbon receptor modulating agent, for 12 weeks led to Physician Global Assessment (PGA) response rates of 35.4% and 40.2%, respectively, in the two phase III trials. Additionally, 36% and 47.6% of patients met the secondary endpoint of at least 75% improvement in the Psoriasis Area and Severity Index (PASI75).

The topical treatment was well tolerated, as most treatment-emergent adverse events (TEAEs) were mild or moderate, Marc Lebwohl, MD, of Icahn School of Medicine at Mount Sinai in New York City, reported during the .

"Tapinarof cream has the potential to be a first-in-class topical therapeutic aryl hydrocarbon receptor modulating agent and provide physicians and patients with a novel nonsteroidal topical treatment option that is highly effective and well tolerated," Lebwohl said in conclusion.

Tapinarof's molecular features address key limitations of existing topical therapies for plaque psoriasis, including restrictions on treatment duration, application site, and issues involving skin sensitivity. The drug binds the intracellular aryl hydrocarbon receptor, and the resulting complex enters the cell nucleus and affects gene expression involved in the production of inflammatory cytokines and barrier proteins.

Currently, the most common topical treatments for plaque psoriasis are "super potent" corticosteroids with treatment duration limited to 2 to 4 weeks. These are not recommended for use on the face or intratriginous sites such as the axilla, Lebwohl noted.

No novel topical therapies have been approved for psoriasis in recent years, he continued.

Key Findings

Tapinarof was evaluated in the phase III and , involving approximately 1,000 patients with plaque psoriasis. About 80% of the patients had moderately severe diseases, with mean PASI scores of 9, and mean body surface area involvement of 8%. More than 80% of the patients had a PGA score of 3 at baseline. In both trials, patients were randomized to once-daily tapinarof 1% or vehicle, and PGA response at 12 weeks (0 or 1 plus at least a 2-point improvement from baseline) was the primary endpoint.

In PSOARING 1, 35.4% of the tapinarof group met the primary endpoint as compared with 6.0% of patients randomized to vehicle (P<0.0001). In PSOARING 2, the PGA response rates at 12 weeks were 40.2% with tapinarof and 6.3% with vehicle (P<0.0001). For the key secondary endpoint of PASI75 response, tapinarof-treated patients had a 25.9% and 40.7% absolute advantage over the control groups in PSOARING 1 and PSOARING 2, respectively.

In both trials, severe and serious TEAEs occurred in 2%-3% of patients treated with tapinarof. Folliculitis was the most commonly reported TEAE (15-20% of patients in each trial) and reached severe status in only one patient treated with tapinarof, said Lebwohl.

Novel Nanodrug

A novel interleukin (IL)-17-targeted, albumin-bound nanobody drug achieved high response rates with limited toxicity in a preliminary dose-ranging clinical trial.

Treatment with the highest dose of sonelokinab led to an IGA 0/1 response rate of 88% at 24 weeks and a PASI90 response rate of almost 80%. About half of patients attained PASI100 responses by 24 weeks.

The drug had a rapid onset of action, and responses tended to be maintained over time. Patients who had inadequate responses to lower doses of sonelokinab had similar rapid and sustained improvement after dose escalation, reported Kim A. Papp, MD, PhD, of Probity Medical Research in Waterloo, Ontario.

"These results support the emerging role of IL-17 as a mechanism of action and are the first important steps in exploring the nanobody platform for the treatment of inflammatory conditions," he concluded.

Inhibition of IL-17 has proven effectiveness for treating psoriasis -- three biologic agents inhibiting IL-17 are now approved -- but sonelokinab represents a novel structural platform for this target. The drug comprises three monovalent camelid nanobodies specific to IL-17F, IL-17A/F, and human serum albumin. In a , the drug achieved dose-dependent improvement in psoriasis with good tolerability.

Papp reported findings from a phase IIb trial evaluating sonelokinab at doses of 30 to 120 mg administered every 2 to 4 weeks. The trial included a total of 313 patients with moderate or severe plaque psoriasis, including a placebo arm and patients randomized to standard-dose secukinumab (Cosentyx), one of the anti-IL-17 agents already approved, as an active comparator. Randomized therapy continued for 12 weeks, followed by maintenance and dose escalation from weeks 12 to 24.

Treatment with the 120-mg dose of sonelokinab led to rapid responses, as about a third of patients achieved PASI90 by 4 weeks, increasing to about 80% at week 12 and almost 90% at week 24, said Papp. Onset of response was faster than that of secukinumab. Peak responses were maintained with sonelokinab but tended to decline over time with secukinumab.

Rates of TEAEs were similar across all groups on active therapy. Nasopharyngitis and upper respiratory tract infections were the most common TEAEs with sonelokinab and secukinumab. Consistent with other agents that target IL-17, sonelokinab was associated with a higher incidence of nonserious oral Candida infections, said Papp.