Soligenix Inc. announced positive results from its Phase 2a proof-of-concept study evaluating SGX945 (dusquetide) for treating Behçet's disease, demonstrating biological efficacy that matched outcomes achieved by the only FDA-approved therapy for this rare inflammatory condition. The open-label study enrolled 8 patients and achieved its primary objective of showing therapeutic benefit in oral ulcers, a hallmark symptom of the chronic autoimmune disorder.
Comparable Efficacy to Approved Standard of Care
The Phase 2a study was designed to be highly comparable to the published Phase 3 study of apremilast (Otezla), which supported marketing approval for oral ulcers in Behçet's disease. Using the same primary endpoint of area under the curve (AUC) - a composite measurement of peak number of oral ulcers and time to resolution - SGX945 demonstrated a 40% improvement relative to the historical placebo group after 4 weeks of treatment, compared to apremilast's 37% improvement.
Notably, SGX945's benefits persisted during the 4-week follow-up period despite treatment cessation at week 4, maintaining a 32% improvement at week 8. In contrast, apremilast required continuous administration through week 12 to achieve a 41% improvement at week 8.
"The benefit of SGX945 was observed in 7 of 8 patients treated in this study, and many patients also commented on the reduced symptoms they experienced in the weeks following treatment as well," stated Dr. Gülen Hatemi, Professor of Medicine at Istanbul University and lead investigator in the study. "As a twice weekly treatment, the durability of the response may indicate a favorable chronic use or maintenance profile for SGX945."
Superior Safety Profile
SGX945 demonstrated a notably cleaner safety profile compared to apremilast. The investigational therapy was well-tolerated with no treatment-related adverse events, while apremilast's common side effects included diarrhea in 41% of patients, nausea in 19%, and headache in 14% - none of which were observed with SGX945.
Seven of 8 patients reported perceived clinical benefit with SGX945 treatment, including reduced duration and number of oral ulcers, and decreased oral pain. One patient who began the study with a punctuated skin ulcer also experienced resolution during the 4-week treatment period, which is particularly significant given that skin ulcers are generally considered very difficult to resolve and usually require protracted treatment.
Addressing Significant Unmet Medical Need
Behçet's disease affects approximately 18,000 people in the United States, 50,000 in Europe, 350,000 in Turkey, and up to 1 million people worldwide. The inflammatory disorder commonly manifests in young adults with mouth sores in approximately 95% of patients, skin rashes and lesions in 50%, genital sores in 50%, leg ulcers in 40%, and eye inflammation in 15% of cases.
Currently, there is no cure for Behçet's disease, with treatments focused on symptom management. Apremilast is the only approved drug specifically for Behçet's disease, used as maintenance therapy to prevent oral ulcer formation. However, it must be used continuously to maintain effectiveness and has had limited international market penetration due to cost considerations in the continuous use setting.
"Given the role of the innate immune system in ulcers associated with Behçet's Disease, and the unmet medical need particularly for more severe ulcers such as genital and skin ulcers, we believe that dusquetide may offer significant relief to patients," stated Christopher J. Schaber, President and CEO of Soligenix.
Novel Mechanism and Development Strategy
SGX945 contains dusquetide, an innate defense regulator (IDR) representing a new class of short, synthetic peptides. The compound has a novel mechanism of action whereby it modulates the body's reaction to both injury and infection toward an anti-inflammatory, anti-infective, and tissue healing response. Unlike direct antibiotic approaches, IDRs work by modulating the host's innate immune system responses.
The Phase 2a study administered SGX945 as a twice-weekly 4-minute intravenous infusion for 4 weeks, followed by 4 weeks of follow-up observation. Patients were aged 18 years or older with mild to moderate Behçet's disease and active oral and/or genital ulcers.
Future Development Plans
Based on these results, Soligenix plans to reformulate SGX945 to enable home-based treatment using subcutaneous injection, similar to approaches used for weight-loss medications. The company intends to interact with health authorities to design a follow-on placebo-controlled Phase 2 study and expand dusquetide's development into different innate immune-related inflammatory conditions.
Dusquetide has previously demonstrated safety and tolerability in a Phase 1 clinical study involving 84 healthy volunteers and has shown positive efficacy results in Phase 2 and 3 studies with over 350 subjects for oral mucositis treatment in head and neck cancer patients.
