- Primary and Secondary Endpoints Achieved with Statistical Significance
- Mizagliflozin Treatment Increases Glucose Nadir and Decreases Peak Glucose and Peak Insulin
DURHAM, NC / June 30, 2023 / Vogenx, a clinical-stage developer of novel therapeutics for the treatment of metabolic disease, today announced positive results from study VGX 001-011 (NCT05541939). This phase 2 study was a multi-center, randomized, sequential crossover, single ascending dose study evaluating mizagliflozin in patients who suffer from post-bariatric hypoglycemia (PBH), a debilitating complication of bariatric surgery leading to recurrent postprandial hypoglycemia with neuroglycopenia.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).
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 PBH. PBH is a disease with growing high unmet medical need and no approved pharmacologic therapy.
Nine patients each received a baseline MMTT and were randomized to one of two treatment arms. Treatment Arm A received a 2.5 and 5.0 mg mizagliflozin capsule at sequential visits. Treatment Arm B received a 2.5 mg mizagliflozin liquid formulation and 10.0 mg 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 hypoglycemia at baseline with a glucose nadir <70 mg/dL, the change from baseline mean glucose nadir for all capsule doses was 19.3 ± 14.7 mg/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 ± 27.9 mg/dL (p = 0.59). These data suggest mizagliflozin is effective in preventing hypoglycemic events without significantly impacting blood glucose levels in patients not experiencing hypoglycemia.
In all subjects, the mean glucose nadir change from baseline for all capsule doses was 12.6 ± 22.5 mg/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 ± 237 uU/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. 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 PBH 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 PBH.
Lead Investigator, Helen Lawler, MD, Associate Professor of Medicine in Endocrinology at the University of Colorado School of Medicine commented on these results, “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.” Dr. Lawler added, “The results comparing patients with glucose nadir above and below 70 mg/dl at baseline are particularly interesting in that it appears the pharmacodynamic effect of mizagliflozin treatment is amplified in patients with more severe symptoms.”
“We are very pleased by the results from Study 011,” said William Wilkison, Ph.D., 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.”
About Mizagliflozin
Mizagliflozin is a novel first in class small molecule therapeutic candidate being developed for PBH. Mizagliflozin has been administered in over 500 subjects in 9 clinical trials and has shown to reduce and delay postprandial glucose absorption and insulin secretion.
About Post-Bariatric Hypoglycemia
PBH is known to be a side effect associated with bariatric surgeries that are commonly performed as a treatment for obesity. Bariatric surgery has proven to be a highly effective treatment for obesity, leading to significant improvements in body mass index and obesity-related co-morbidities.
There are currently no therapeutics approved by the FDA for the treatment of PBH. PBH is a form of reactive postprandial hypoglycemia that often presents 6 months to several years post-surgery. Hypoglycemic events in patients diagnosed with PBH are caused by rapid increases in postprandial circulating glucose and a corresponding uncontrolled spike in insulin, typically 1-2 hours after a meal. Symptoms may be mild, moderate or severe and can include those associated with neuroglycopenia such as shakiness, hunger, dizziness, confusion, sweating and loss of consciousness that can dangerously impair normal day-to-day activities and can be life-threatening. Severe PBH can be debilitating with a significant negative impact on quality of life.
About Vogenx, Inc.
Vogenx, Inc. is a clinical-stage life science company based in Durham, North Carolina. The Company is focused on the development of novel therapeutics for the treatment of rare and metabolic diseases with high unmet medical need. For more information about Vogenx, please visit https://vogenx.com
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SOURCE: Vogenx, Inc.