Safety of TCMCB07, a melanocortin-4 antagonist peptide, in dogs with naturally occurring cachexia

Background: The melanocortin 4 antagonist TCMCB07 is safe and effective in reversing cachexia caused by sepsis or cancer in rodents. The safety and pharmacokinetics of TCMCB07 are demonstrated in healthy beagle dogs. Hypothesis/Objectives: The objectives of this study were to investigate the safety, peak plasma concentrations, and potential for efficacy of TCMCB07 in pet dogs with naturally occurring cachexia over a 4-week time period. Animals: Fourteen dogs with cachexia of any underlying cause, except cancer of the oral cavity or gastrointestinal tract, were eligible for enrollment with informed client consent. Methods: This study was a prospective, 1-armed open-label trial. Physical examination, complete blood count, chemistry panel, and owner-assessed quality of life surveys were checked at weeks 1, 2, and 4. Due to potential for bradycardia and hypotension, Holter monitoring and blood pressure evaluations were scheduled at pre-enrollment and week 4. Results: Fourteen dogs completed the trial. Significant changes detected included increased mean body weight (18.6-19.5 kg, P <.02), increased body condition score (median Tufts 5-point thin dog scale score P <.004 and WSAVA muscle condition score P <.02) and increased mean blood urea nitrogen (21.79-30.43 mg dL⁻¹, P <.004). On quality of life surveys, pet owners perceived their dog appeared to be panting less (P <.002) and that the general health improved (P <.03). Four dogs had a change in coat pigmentation. The peak plasma concentration of TCMCB07 in cachectic dogs was similar to that in healthy beagle dogs. Conclusions and Clinical Importance: TCMCB07 was safe and has potential efficacy in pet dogs with cachexia.