COPENHAGEN – An ultrasmall yet highly potent single-chain antibody fragment directed against tumor necrosis factor–alpha showed promise for the treatment of Behçet’s disease flares in a pilot phase II study presented at the annual congress of the European Academy of Dermatology and Venereology.
“We believe that we have something in our hands that may make a difference to these patients. Further development with follow-up studies is planned,” said Dr. Thomas Jung, chief medical officer at Delenex Therapeutics.
The agent, known for now as DLX105, utilizes the company’s proprietary PentraBody platform. DLX105 inhibits soluble as well as membrane-bound TNF-alpha. Because the protein antibody is so small, it has the capacity to penetrate into inflamed tissue, be it skin or cartilage. DLX105 is also being explored as a potential therapy for other flaring inflammatory skin and autoimmune disorders, he added.
“The antibody also leaves the tissue very rapidly. It doesn’t stick around as long as an IgG antibody. The typical half-life of this molecule is about 1 day. We believe this is actually an advantage when we talk about treating a flaring disease such as Behçet’s, where we want exposure for a certain time frame, but we don’t want to overexpose the patient over weeks and months when it is not really necessary,” Dr. Jung explained.
Behçet’s disease is a chronic autoimmune vasculitic disease which presents most often as oral ulcers, papulopustular skin lesions, genital ulcers, uveitis, and/or arthritis. Cardiac, gastrointestinal, and CNS involvement occurs less frequently. The pathogenesis of the disease is unknown; no specific cause or triggers have been identified. Behçet’s disease affects an estimated 20,000 people in the United States, but is far more common in Turkey, the Middle East, and Asia. All treatment is off-label; there is no approved therapy for Behçet’s disease. The most widely used agents are corticosteroids, colchicine, and cyclosporine, with the biologic TNF inhibitors often being utilized in an effort to prevent blindness when uveitis occurs.
Dr. Jung presented results of the small phase II open-label study, which involved six patients with Behçet’s disease for a mean of 10 years. All presented with a disease flare. All six had oral aphthous ulcers, four had skin lesions, three had joint pain, two had erythema nodosum, and one had genital ulcers. All participants received a single intravenous infusion of DLX105 at 10 mg/kg.
All of the oral ulcers healed within 1 week following the single dose of DLX105. Patients with joint pain reported it was substantially improved within 1-2 days after treatment. Genital lesions healed completely within 2 weeks. The skin lesions were also markedly improved. The clinical improvement was maintained up to 4 weeks post treatment.
The improvement in joint symptoms was not unexpected. DLX105 has been shown to inhibit human TNF-alpha–induced joint swelling in rats with an efficacy comparable to infliximab (Remicade), according to Dr. Jung.
Perhaps most impressively, Dr. Jung observed, erythema nodosum healed completely in both affected patients. Erythema nodosum can be notoriously difficult to treat. Indeed, one of the patients had erythema nodosum for 5 years during which multiple systemic therapies were employed without benefit.