TTP273, an oral, non-peptide GLP-1R agonist showed significant placebo-subtracted reductions in A1c of 0.9 and 0.7% when dosed at 150mg QPM or BID, respectively, in LOGRA, a 12-week, phase 2, double-blind, placebo-controlled randomized study [Diabetes 2017 Jun; 66 (S 1) A326]. In addition, less nausea was observed in the active groups than in the placebo group and the only incidence of vomiting occurred in the placebo group.

A post hoc analysis of patients from the LOGRA study with Stage 2 hypertension that completed 12 weeks of dosing revealed a subgroup with a nominally statistically significant reduction in systolic blood pressure (SBP). Entry criteria allowed patients on standard of care treatment for hypertension, but excluded patients with persistent, uncontrolled hypertension at screening (SBP ≥ 160mmHg and/or diastolic blood pressure (DBP) ≥ 90mmHg). Approximately 25% of the patients that completed the study were considered to have Stage 2 hypertension at baseline (defined by SBP ≥ 140mmHg or DBP ≥90mmHg) and around 75% of those patients received 1 or more concomitant medications to treat hypertension.

Among treatment groups, characteristics were relatively well balanced with an approximately equal number of patients enrolled per treatment group with similar baseline values for SBP/DBP and pulse rate among treatment groups (mean baseline values of 147/85 mmHg and 73 bpm). The post hoc analysis demonstrated a mean decrease from baseline in SBP of 17 in the 150mg QPM arm (n=9) (p < 0.05 vs. placebo), 12 in the 150mg BID TTP273 arm (n=10) and of 6 mmHg in the placebo arm (n=8), respectively. No significant changes in DBP or pulse rate were observed with either active group compared to placebo.

Results from this post hoc analysis suggest that TTP273 could provide an additional benefit of reducing SBP, in line with other GLP-1R agonists. Unlike other GLP-1R agonists, these effects occurred without the side effects of nausea and vomiting.

Disclosure

C. Valcarce: Employee; Self; vTv Therapeutics. I. Dunn: None. J.L.R. Freeman: Employee; Self; vTv Therapeutics. Stock/Shareholder; Spouse/Partner; vTv Therapeutics.

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