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Promising results with nanobody treatment in psoriasis

Presented By
Dr Kim A. Papp, Probity Medical Research, Canada
EADV 2020
Phase 2

A phase 2b trial showed significant and clinically meaningful benefits of sonelokinab compared with placebo in moderate-to-severe chronic plaque psoriasis.

Sonelokinab is a trivalent camelid nanobody comprised of 2 active elements, an IL-17F moiety and an IL-17A/F moiety, bound to albumin as central moiety. Binding with albumin prolongs the half-life to 10-12 days,” explained Dr Kim A. Papp (Probity Medical Research, Canada) [1]. The multicentre, double-blind, phase 2b trial investigated the efficacy and safety of sonelokinab (formerly known as M1095) in the treatment of moderate-to-severe chronic plaque psoriasis. Participants (n=313) were randomised into 6 arms: 3 groups received sonelokinab subcutaneously at doses 30 mg, 60 mg, and 120 mg (at weeks 0, 2, 4, and subsequently every 4 weeks); 1 group received an enhanced loading dose of sonelokinab 120 mg every 2 weeks through to week 12; 1 group received a placebo; and 1 group received secukinumab according to the labelled dosage.

From week 12 to week 24, dose escalation was performed. “Patients in the 30-mg and 60-mg arms were treated according to their week 12 Investigator Global Assessment [IGA] response: those achieving IGA ≤1 continued on the original dose; patients with IGA response >1 received 120 mg at week 12 and every 4 weeks thereafter,” described Dr Papp. Sonelokinab recipients with a normal loading dose of 120 mg continued with 120 mg every 8 weeks. Patients with 120 mg enhanced loading stayed on the same dose, administered every 4 weeks, and placebo patients were switched to sonelokinab 120 mg at week 12, 14, 16, and every 4 weeks thereafter. The secukinumab arm continued per the labelled dose. The mean age of the 313 participants was 46 years, 27% were women, they had 18.3 years of disease duration, and 16% had had prior exposure to biologics. Mean baseline PASI was 20.8, 74% had IGA 3 and 26% IGA 4. The primary endpoint was IGA 0/1 at week 12 compared with placebo.

All comparisons for sonelokinab versus placebo were significant for superiority of sonelokinab at week 12 (summary P≤0.002). At week 12, rates for the highest dose of sonelokinab were: 88.2% IGA 0/1 (95% CI 76.1-95.6), 76.5% PASI 90 (95% CI 62.5-87.2), 33.3% PASI 100 (95% CI 20.8-47.9). At week 24, percentages of patients achieving IGA 0/1 were between 80.4% and 94.2% in the higher-dose sonelokinab cohorts. The corresponding rates for PASI 90 and PASI 100 varied from 79.2% to 90.4% and 40.4% to 56.9%, respectively. “Patients treated with secukinumab experienced a progressive improvement in PASI 90 to about 80% by week 24; patients treated with sonelokinab 120 mg every 8 weeks had a response trajectory very similar to that of secukinumab, and patients in the sonelokinab 120 mg enhanced load every 4 weeks achieved superior responses at all timepoints,” Dr Papp pointed out.

Commenting on the results, Dr Papp made 2 general observations: “Looking at the overall response through 12 weeks for IGA 0/1, PASI 90, and PASI 100, there appears to be a clear dose response across the sonelokinab arms, with secukinumab running roughly in the middle. If I draw your attention back to the first 3 weeks, for the IGA 0/1 or PASI 90 responses, sonelokinab-treated patients consistently showed more rapid responses. This very rapid response may reflect the ability of sonelokinab to get to the target tissue faster because of its low molecular weight.”

As for safety, 51.4% of study subjects had a treatment-emergent adverse event (TEAE). “We see that in all dose groups, the occurrence of TEAE is similar with a trend to a slightly higher incidence in the treatment groups compared with placebo. Nasopharyngitis and upper respiratory tract infections were the dominant adverse events. Consistent with the mechanism of action, there was a trend of an increased incidence of candidiasis with increased IL-17 blockade,” evaluated Dr Papp.

“These results support the emerging role of the IL-17A/F mechanism of action and other first important steps in exploring the nanobody platform for the treatment of inflammatory conditions,” concluded Dr Papp.

    1. Papp KA, et al. A Phase 2B, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study Assessing the Efficacy, Safety, and Tolerability of Sonelokinab (M1095), an IL-17A/F Nanobody, in Patients with Moderate-to-Severe Chronic Plaque Psoriasis: Results from 24 Weeks. D1T03.3B, EADV 2020 Virtual Congress, 29-31 Oct.

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