First in Class mTOT Modulator Meets Phase 2b Study Endpoints

June 9, 2012

In a recently completed Phase 2b study, MSDC-0160, a novel once-a-day oral insulin sensitizer and a prototype first in a new class of therapeutic agents called mTOT Modulators, which are being developed by researchers at Metabolic Solutions Development Company (MSDC), met the primary endpoint of significantly reducing fasting plasma glucose (FPG) in patients diagnosed with type 2 diabetes, and significantly reduced hemoglobin A1c (HbA1c).

Of particular importance, the data showed that changes in body weight, hemoglobin, and an important biomarker linked to production of white fat were significantly less in type 2 diabetic patients treated with MSDC-0160 than in patients treated with a comparator drug, pioglitazone 45 mg.

These results affirm MSDC’s hypothesis that insulin sensitization is controlled through a newly defined, mitochondrial protein complex identified as mTOT. mTOT functions as a molecular “sensor switch” connecting mitochondrial metabolism to important cellular activities, such as carbohydrate, lipid, and amino acid metabolism, that are out of balance in patients with type 2 diabetes.

This study was a 90-day, randomized, double-blind, comparator- and placebo-controlled, multi-dose study in 266 patients with type 2 diabetes. The study compared three doses of MSDC-0160 (50 mg, 100 mg and 150 mg) to maximum dose Actos (pioglitazone) (45 mg) or placebo taken orally once daily for 12 weeks. All treatments were well tolerated. There were no serious adverse events attributed by investigators to the MSDC drug.

Key top-line data from this study include the following:

  • Both 100 mg/day and 150 mg/day of MSDC-0160 significantly lowered fasting plasma glucose (primary study endpoint).
  • Both 100 mg/day and 150 mg/day of MSDC-0160 lowered hemoglobin A1c similar to 45 mg/day pioglitazone.
  • MSDC-0160 produces significantly less volume expansion than pioglitazone at any dose.  There was a statistically significant difference between MSDC-0160 and pioglitazone in the effects the compounds on circulating hemoglobin and red blood cells.
  • No dose of MSDC-0160 was able to increase adiponectin as much as pioglitazone, supportive of less effect on calorie storing white adipose tissue (i.e., white fat).
  • The 100 mg dose of MSDC-0160 was effective with significantly less weight gain.  Moreover, given the differential effects on adiponectin, pioglitazone weight gain may involve more increase in white adipose tissue than any dose of MSDC-0160.