R04 - Evaluation of Sobetirome for Pulmonary Fibrosis in West Highland White Terriers

Abstract: Background: Pulmonary fibrosis (PF) a fatal disease with no current therapy. In a mouse model, the thyroid mimetic, sobiterome, ameliorated histopathological evidence of fibrosis.

Hypothesis/Objectives Sobetirome will improve exercise tolerance and decrease pulmonary hypertension in dogs with PF. Therapy with sobiterome will decrease cholesterol and T4 without other side effects.

Animals – Healthy beagles, West Highland White terriers (WHWT) with PF

Methods – Safety study; Six beagles were administered Sobetirome over 2 weeks. Pilot clinical trial. WHWT were evaluated with non-sedated CT, echocardiography for determination of tricuspid regurgitant velocity (TRV), 6 minute walk test (6MWT) and cholesterol /T4 measurement at baseline and after at least 6 months of treatment. Results were compared using a paired T-test or Mann-Whitney Rank-Sum.

Results – All beagles completed the study without complications. Cholesterol and T4 decreased (P < 0.001). In WHWT, 13 dogs were recruited, and 6 dogs completed the study. Of the 7 dogs that did not complete the study, three died of PF, two owners withdrew and two moved. 5/6 dogs had TRV > 3.2 m/sec at enrollment, and this increased over the study. (p =0.01) Cholesterol and thyroid decreased insignificantly (p=0.17 and p=0.15). 6MTW was unchanged (p =0.71).

Conclusions and clinical importance – Sobetirome is well-tolerated in dogs and decreases cholesterol and T4 in beagles. PF is a heterogenous disease with variable progression. There was no clear benefit to therapy in this small pilot study of dogs with PF. Clinical trials during COVID were challenging.