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Patients with moderate to severe hidradenitis suppurativa failing adalimumab therapy, or those ineligible to receive it, remain a population with an unmet need. Twenty patients not eligible for adalimumab were randomized to receive 12 weeks of blind treatment with placebo or MABp1, a true human antibody targeting IL-1α. Hidradenitis suppurativa clinical response score at week 12 was the primary endpoint. The primary endpoint was met in 10% and 60% of placebo- and MABp1-treated patients, respectively (odds ratio = 13.50, 95% confidence interval = 1.19-152.51). Clinical efficacy was maintained at 24 weeks in 0% and 40%. Improvement in the visual analog scale was reported by 20% and 85.7%, respectively, of patients failing previous anti-TNF treatment. Ultrasonography showed decreased neovascularization and lesion skin depth in the MABp1 group. MABp1 treatment was associated with decrease of circulating IL-8 and of stimulated production of IL-8 by whole blood. Whole blood production for hBD-2 was negatively associated with changes on ultrasonography in the placebo group but not in the MABp1 group. MABp1 is a promising treatment for patients with hidradenitis suppurativa not eligible for adalimumab. Inhibition of neovascularization and modulation of the production of IL-8 and hBD-2 are suggested mechanisms of action.

Background Advanced non-small cell lung cancer (NSCLC) patients were treated as part of a Phase I dose escalation and expansion study evaluating a true human monoclonal antibody targeting IL-1α (Xilonix), which is intended to modulate the malignant phenotype—inhibiting tumor growth, spread and offering relief of symptoms. Methods Sixteen NSCLC patients were included. Patients failed a median of 4 chemotherapy regimens, including 10/16 failing anti-EGFR therapy. Disease progression was evaluated using a multi-modal approach: tumor response, patient reported outcomes (EORTC-QLQC30), and lean body mass (LBM). Patients received infusions every two or three weeks until progression, and were followed 24 months to assess survival. Results There were no infusion reactions, dose-limiting toxicities, or deaths due to therapy. Albeit not statistically significant, there was a trend in IL-6 (−2.6±18.5 (0.1 [−2.8-2.4]), platelet counts (−11±54 (−4[−36.0-1.0]), CRP (−3.3±30.2 (0.4 [−10.7-1.8]) and LBM (1.0±2.5 (0.4 [−0.5-2.6]). Self-reported outcomes revealed reductions in pain, fatigue and improvement in appetite. Median survival was 7.6 (IQR 4.4-11.5) months, stratification based on prior anti-EGFR therapy revealed a median survival of 9.4 months (IQR 7.6-12.5) for those pretreated (N=10) versus a survival of 4.8 months (IQR 4.3-5.7) for those without (N=6, logrank p=0.187). Conclusion Xilonix was well tolerated, with gains in LBM and improvement in symptoms suggesting a clinically important response. Although not statistically significant, the survival outcomes observed for patients with and without prior anti-EGFR therapy raises intriguing questions about the potential synergy of IL-1α blockade and anti-EGFR therapy. Further study for this agent in NSCLC is warranted.

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