Background Cancer cachexia is characterized by weight loss and is associated with increased morbidity and mortality in patients with cancer. Anamorelin (ONO‐7643; ANAM) is a novel and selective ghrelin receptor agonist that improves appetite, lean body mass (LBM), body weight, and anorexia. Methods This multicenter, open‐label, single‐arm study investigated the efficacy and safety of 100 mg anamorelin in 50 Japanese patients with advanced and unresectable gastrointestinal (colorectal, gastric, or pancreatic) cancer. ANAM was administered once daily over 12 weeks. The primary endpoint was the proportion of patients that maintained or gained LBM over the course of the study. Secondary endpoints included changes in LBM, body weight, quality of life (QoL), and nutritional status biomarkers. Results The proportion of patients who responded to treatment was 63.3% (95% CI, 48.3%‐76.6%), with a least square mean ± SE change in LBM and body weight from baseline of 1.89 ± 0.36 kg and 1.41 ± 0.61 kg, respectively. Appetite‐related questions on the QoL questionnaire showed that ANAM improved appetite. Adverse events occurred in 79.6% of patients, and the most common treatment‐related adverse events were increased γ‐glutamyl transpeptidase (8.2%), diabetes mellitus (6.1%), hyperglycemia (6.1%), and prolonged QRS complex (6.1%). Conclusions ANAM improved anorexia and patients' nutritional status, resulting in rapid increases in LBM and body weight in patients with advanced gastrointestinal cancer who had cancer cachexia. ANAM treatment was well tolerated over 12 weeks. ANAM is a potential clinically beneficial pharmacotherapeutic option for patients with advanced gastrointestinal cancer who have cancer cachexia.

We examined the efficacy, safety, and tolerability of ONO‐4474 in Japanese patients with osteoarthritis (OA) of the knee. In this multicenter, placebo‐controlled, randomized, double‐blind, parallel‐group comparative study, patients with moderate to severe OA who were refractory to nonsteroidal anti‐inflammatory drugs were orally administered 100 mg of ONO‐4474 twice daily for 28 days. The primary end point was knee pain during walking, assessed by visual analog scale over 24 hours (VAS24). Treatment‐emergent adverse events (TEAEs) and adverse drug reactions were reported for safety. In total, 110 patients were randomized (1:1) to receive placebo or ONO‐4474. The mean (standard deviation) change in VAS24 scores at week 4 was −26.9 (25.0) mm in the ONO‐4474 group and −19.5 (19.6) mm in the placebo group. The difference (ONO‐4474 group − placebo group) in posterior mean change in VAS24 at week 4 was −5.8 (posterior standard deviation, 4.4; 95% confidence interval, −14.3 to 2.8) mm. TEAEs were reported in 41.8% of patients in the ONO‐4474 group and 18.2% of patients in the placebo group. The most common TEAEs in the ONO‐4474 group related to the musculoskeletal system and the peripheral and central nervous systems were myalgia (7.3%), arthralgia (5.5%), dizziness (3.6%), and hypoesthesia (3.6%). Four patients from the ONO‐4474 group and 1 patient from the placebo group discontinued treatment because of AEs; however, none were judged to be serious, and all patients recovered or were recovering after discontinuation. ONO‐4474 is a novel tropomyosin receptor kinase inhibitor that has an analgesic effect in patients with OA.