title: Neovastat (AE-941), an inhibitor of angiogenesis: Randomized phase I/II clinical trial results in patients with plaque psoriasis.
abstract: There is considerable evidence to support an immunopathogenic basis of psoriasis. However, changes such as altered angiogenesis have also been implicated in the pathogenesis of psoriasis. AE-941 (Neovastat; Aeterna Laboratories, Quebec City Quebec, Canada) is a naturally occurring product currently in clinical investigation that blocks two main mechanisms of angiogenesis activation, namely, vascular endothelial growth factor and matrix metalloproteinase. We hypothesized that psoriasis could be modulated by inhibiting the neovascularization of psoriatic plaques. We conducted a randomized dose-comparison trial to evaluate the safety and potential therapeutic benefit of AE-941, administered orally to patients with psoriasis. Forty-nine patients with psoriasis were enrolled and assigned to receive AE-941 at 30, 60, 120, or 240 mL/d for 12 weeks. Patients were followed up for another 12-week period. Improvement in the Psoriasis Area and Severity Index (PASI) score was observed in 50%, 41.7%, and 30.8% of the patients receiving 240, 120, and 60 mL/d, respectively. No patients receiving a dosage 30 mL/d showed a PASI score improvement. A statistically significant improvement with increasing dose was observed for the PASI score, severity of itch, and the physician's global assessment. The most commonly reported nonserious drug-related adverse events affected the gastrointestinal system in 12 of 49 patients (primarily nausea, diarrhea, vomiting, flatulence, and constipation) and the skin and appendages in 4 of 49 patients (primarily acne and rash). This randomized phase I/II study provides evidence that the antiangiogenic agent AE-941 offers a new therapeutic approach to the management of psoriasis.
authors.affiliation: Department of Dermatology, Johns Hopkins University, School of Medicine, Baltimore, Maryland 21287, USA.
authors.forename: Daniel N
authors.initials: DN
authors.lastname: Sauder
authors.forename: Joel
authors.initials: J
authors.lastname: Dekoven
authors.forename: Pierre
authors.initials: P
authors.lastname: Champagne
authors.forename: Daniel
authors.initials: D
authors.lastname: Croteau
authors.forename: Eric
authors.initials: E
authors.lastname: Dupont
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003879:Dermatologic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy*; D014020:Tissue Extracts / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D003879:Dermatologic Agents; D014020:Tissue Extracts; C111481:shark cartilage extract