Targeted Genetics Corp (SEATTLE, Washington) reported additional interim data from its phase I/II clinical study of tgAAC94, an investigational therapeutic designed to inhibit the activity of TNFα, in patients with inflammatory arthritis. The study is designed to assess the safety and potential effect of multiple doses of tgAAC94 administered directly to affected joints of inflammatory arthritis subjects with or without concurrent use of systemic TNF antagonist therapies. The data for 66 patient-reported outcomes demonstrated a 30% decrease in the global visual analog scale, a pain assessment tool, in 21/50 (42%) of subjects and in 3/16 (19%) placebo subjects 12 weeks after the first intra-articular injection. A two-point decrease in swelling was noted in 8/50 (16%) treated subjects and in 3/16 (19%) placebo subjects 12 weeks after the first injection. Thus, patient-reported outcome measures of clinical response yielded greater differentiation between tgAAC94 and placebo than physical examination. MRI was performed on treated joints in a subset of subjects and a decrease in effusion was noted in 1/10 of them.

The trial met safety endpoints. A total of 127 subjects received the first injection of blinded study drug and 95 of them received a second injection of open-label study drug. The drug resulted in administrative site reactions following 12% of injections, but was otherwise well-tolerated. Serious adverse events included a culture negative septic arthritis, which was determined to be probably related to tgAAC94; a case of fatal disseminated histoplasmosis in a subject receiving systemic anti-TNF therapy, which was ultimately deemed unrelated to study agent; and 10 other unrelated events. Patients continue to be followed for safety and measures aimed to assess functional improvement in treated joints.

Additional clinical trial protocols are currently being developed to evaluate efficacy and duration of response, as well as to further assess safety in patients with inflammatory arthritis who have ≤1 inflamed joints and who are not candidates for systemic therapy or who do not fully respond to systemic anti-TNF protein therapy.

The product candidate uses Targeted Genetics' recombinant Adeno-Associated Virus (rAAV) vector technology to deliver a DNA sequence that encodes a soluble form of TNFα receptor (TNFR: Fc). Soluble TNFR:Fc inhibits the immune stimulating activity of TNFα. Direct injection of tgAAC94 into affected joints leads to the localized production of secreted TNFR:Fc within joint cells, reducing the activity of TNFα within the joint and, potentially, leading to a decrease in the signs and symptoms of inflammatory disease and inhibition of joint destruction.