Vogenx has announced positive results from its VGX 001-011 study, a phase 2 multi-centre, randomised, sequential crossover, single ascending dose study evaluating mizagliflozin in patients who suffer from post-bariatric hypoglycaemia. The study examined four doses of mizagliflozin in patients randomly assigned to one of two treatment arms. Safety, tolerability and pharmacodynamic response to mizagliflozin were assessed during a mixed meal tolerance test (MMTT).
"Using mizagliflozin as a targeted blockade of SGLT1 in the intestinal lumen, which is the primary mechanism for absorption of glucose, significantly reduced postprandial insulin peaks and increased postprandial glucose nadir levels across all administered doses." Said lead Investigator, Dr Helen Lawler, Associate Professor of Medicine in Endocrinology at the University of Colorado School of Medicine commented on these results. "The results comparing patients with glucose nadir above and below 70mg/dl at baseline are particularly interesting in that it appears the pharmacodynamic effect of mizagliflozin treatment is amplified in patients with more severe symptoms."
Mizagliflozin is a first-in-class, orally available small molecule inhibitor of the sodium-dependent glucose transporter-1 (SGLT1), in Phase 2 clinical development for post-bariatric hypoglycaemia.
Nine patients each received a baseline MMTT and were randomised to one of two treatment arms. Treatment Arm A received a 2.5 and 5.0mg mizagliflozin capsule at sequential visits. Treatment Arm B received a 2.5mg mizagliflozin liquid formulation and 10.0mg mizagliflozin capsule at sequential visits. Mizagliflozin doses were administered 20 minutes prior to MMTT administration. Pharmacodynamic samples were taken at various times from 0‑180 minutes, and glucose and insulin profiles determined.
The primary endpoints were safety and change in glucose nadir from baseline. Secondary endpoints included change from baseline peak plasma glucose and peak insulin. Levels of glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) were examined as exploratory endpoints in a subset of patients.
In patients experiencing hypoglycaemia at baseline with a glucose nadir <70mg/dL, the change from baseline mean glucose nadir for all capsule doses was 19.3±14.7mg/dL (p=0.013); patients with glucose nadir at baseline ≥70 mg/dL showed a change from baseline mean glucose nadir for all capsule doses of 6.0±27.9mg/dL (p=0.59). These data suggest mizagliflozin is effective in preventing hypoglycaemic events without significantly impacting blood glucose levels in patients not experiencing hypoglycaemia.
In all subjects, the mean glucose nadir change from baseline for all capsule doses was 12.6±22.5mg/dL (p=0.045). The mean peak glucose change from baseline for all capsules was -29 ± 36.4 mg/dL (p=0.027). The mean peak insulin change from baseline for all capsules was -165±237uU/ml (p=0.012). In the subset analysis, mizagliflozin showed no significant effect on circulating GLP-1. In contrast, all mizagliflozin treatments in the subset analysis showed decreased peak GIP levels and AUC0-3h compared to baseline.
Mizagliflozin was well-tolerated and there were no treatment-related serious adverse events and no participant withdrawals. Adverse events were mild with the most common being nausea and abdominal bloating.
These data are consistent with previous clinical studies that showed mizagliflozin was safe and well tolerated. In addition, mizagliflozin is effective in preventing hypoglycemia in post-bariatric hypoglycaemia patients, by reducing both postprandial peak glucose and peak insulin. These results are strongly supportive of further development of mizagliflozin as an orally administered treatment for post-bariatric hypoglycaemia, the company said.
"We are very pleased by the results from Study 011," said Dr William Wilkison, Chief Scientific Officer at Vogenx. "Mizagliflozin treatment consistently led to clinically meaningful improvements in both glucose and insulin while reducing postprandial hyperinsulinemic hypoglycemia and associated signs and symptoms. We look forward to continuing the development of mizagliflozin as a treatment for PBH."