SAN DIEGO — Velusetrag, an oral, highly selective 5-hydroxytryptamine receptor 4 agonist, effectively reduced symptoms and gastric emptying in patients with diabetic or idiopathic gastroparesis, according to research presented at Digestive Disease Week.
Braden Kuo, MD, of Massachusetts General Hospital, said that while prokinetic agents have shown to be helpful in patients with gastroparesis, many of the agents have cardiac side effects that are linked to neurologic issues, leaving long-term options for treatment limited.
“Velusetrag [Theravance Biopharma] is a potent and very selective agonist,” he said in his presentation. “It does not have any significant affinity for any other receptor types, including the 5-HT, the 5-HT2 or 5-HT3 and other dopamine receptors, or other ion channels.”
Researchers assessed the efficacy of velusetrag in a phase 2b study composed of 232 patients with delayed gastric emptying and gastroparesis symptoms — defined as Gastroparesis Cardinal Symptom Index (GCSI) total score of at least 2.5.
They randomly assigned patients to receive either 5 mg, 15 mg or 30 mg of velusetrag or placebo for 12 weeks. The primary efficacy measure was the change from baseline to week 4 in 7-day mean composite score from the GCSI-24H for each treatment arm compared with placebo. Investigators also assessed day 28 gastric emptying using gastric emptying scintigraphy (GES).
Patients who received the 5 mg dose of velusetrag experienced a –1.5±0.13 change in GCSI-24H score at week 4 compared with a –1.1±0.13 change among those who received placebo (P = .03). Patients in the 15 mg and 30 mg groups experienced –1.2 ± 0.14, and –1.0 ± 0.13 changes, respectively. At week 12, 5 mg of velusetrag numerically reduced GCSI-24H total score compared with placebo (treatment difference –0.3; 95% CI, –0.73 to 0.1).
Investigators noted similar changes from baseline in both patients with diabetic and idiopathic gastroparesis. However, the treatment effect in patients with diabetes was smaller because of a large placebo effect.
Kuo and colleagues found that 44% of patients in the 5 mg group, 65% of patients in the 15 mg group and 71% of patients in the 30 mg group achieved normalization of gastric emptying (defined as a < 10% reduction in GES hour-4 retention) compared with 0% of patients in the placebo group.
Velusetrag was also well-tolerated among patients. The most common adverse events were diarrhea, nausea and headache across all treatment groups.
“These findings set the stage for phase 3 studies assessing the efficacy of velusetrag in patients with gastroparesis with a focus on the optimal velusetrag dosing to achieve maximal symptomatic and prokinetic effects,” Kuo said. – by Alex Young
Abell T, et al. Abstract 784. Presented at: Digestive Disease Week; May 18-21, 2019; San Diego.
Disclosures: Kuo reports grant funding from AstraZeneca, Evidera, Gelesis, Genzyme, GSK, Medtronic, Takeda, Theravance and Vanda. He also reports personal fees from Actavis Pharma, AstraZeneca, Biogen, Entrega, Forest Pharmaceuticals, Gelesis, Genzyme, GSK, Ironwood Pharmaceuticals, Medtronic, Takeda and Theravance. Please see the meeting disclosure index for all other authors’ relevant financial disclosures.