Phenomix Announces Positive Results from a Phase 3 Study ofDutogliptin in Type 2 Diabetes Mellitus
San Diego, Calif. - April 20, 2010 - Phenomix Corporation today announced positive top-line results from a six-month Phase 3 study comparing dutogliptin 400mg and 200mg once daily as monotherapy versus placebo for the treatment of patients with Type 2 diabetes mellitus. Dutogliptin is Phenomix' internally-discovered dipeptidyl peptidase-4 (DPP-4) inhibitor.
In this study, patients with moderately elevated baseline hemoglobin A1c (HbA1c) levels (mean: 8.19%) treated with dutogliptin showed statistically significant reductions of HbA1c versus placebo at week 24, the primary endpoint of the study. Reductions in HbA1c corrected for placebo effects were 0.59% for the 400mg dose (p <0.0001) and 0.28% for the 200mg dose (p <0.0138). The results are similar to published data from trials evaluating other drugs from the DPP-4 inhibitor class.
Statistical significance was observed at the 400mg dose for all secondary endpoints, which included change from baseline in fasting and peak postprandial plasma glucose, change from baseline in glucose AUC (0-2 hours) after a standard test meal, and percentage of subjects reaching treatment goal of HbA1c of less than 7.0%. Additional ongoing Phase 3 studies are evaluating the safety and efficacy of dutogliptin utilizing the 400mg dose in combination with metformin, sulfonylurea and pioglitazone.
In this monotherapy Phase 3 study, dutogliptin was well tolerated. The percentages of subjects reporting adverse events, discontinuing due to adverse events and reporting serious adverse events were similar in the dutogliptin and placebo groups. The table below lists the adverse events reported with a frequency of greater than or equal to 2% in any treatment group.
Placebo N=133 Dutogliptin 200mg N=138 Dutogliptin 400mg N=273
At least one common adverse event 47 (35.3%) 37(26.8%) 77 (28.2%)
Urinary tract infection 13 (9.8%) 8 (5.8%) 13 (4.8%)
Dyslipidaemia 7 (5.3%) 4 (2.9%) 15 (5.5%)
Headache 6 (4.5%) 5 (3.6%) 10 (3.7%)
Diarrhea 3 (2.3%) 3 (2.2%) 8 (2.9%)
Nasopharyngitis 1 (0.8%) 2 (1.4%) 8 (2.9%)
Back pain 5 (3.8%) 1 (0.7%) 8 (2.9%)
Hypertriglyceridaemia 8 (6.0%) 3 (2.2%) 6 (2.2%)
Upper respiratory tract infection 4 (3.0%) 1 (0.7%) 8 (2.9%)
Anaemia 0 3 (2.2%) 4 (1.5%)
Arthralgia 1 (0.8%) 4 (2.9%) 1 (0.4%)
Blood CPK increase 1 (0.8%) 3 (2.2%) 2 (0.7%)
Diabetic neuropathy 3 (2.3%) 1 (0.7%) 4 (1.5%)
Nausea 4 (3.0%) 2 (1.4%) 3 (1.1%)
Myalgia 1 (0.8%) 3 (2.2%) 1 (0.4%)
Cough 3 (2.3%) 0 2 (0.7%)
Haematuria 3 (2.3%) 1 (0.7%) 1 (0.4%)
Pyrexia 3 (2.3%) 1 (0.7%) 1 (0.4%)
"We are very pleased with the results of this successful Phase 3 trial with dutogliptin. These results suggest that dutogliptin will provide clinically important glycemic control with potential improvements in tolerability in patients with Type 2 diabetes," said Laura K. Shawver, Ph.D., Chief Executive Officer of Phenomix Corporation.
Forest Laboratories today announced its decision to terminate its collaboration with Phenomix for the development and commercialization of dutogliptin for business reasons. "We are disappointed that on the heels of such positive Phase 3 data that we will not be moving forward with our collaboration with Forest. We expect to be talking to new prospective partners soon," added Dr. Shawver.
These top-line results are consistent with previously announced positive findings from a 12-week, Phase 2b study in which dutogliptin met all primary and secondary endpoints, including statistically significant reductions in HbA1c when administered once daily in combination with metformin, a glitazone, or metformin and a glitazone for the treatment of Type 2 diabetes. In the Phase 2b trial, dutogliptin was well tolerated. The results were recently published in Diabetes, Obesity and Metabolism. (i)
About the PROT301 Study
PROT301 was a 24-week, multi-center, randomized, double-blind, parallel group, placebo-controlled Phase 3 trial that evaluated the efficacy, safety and tolerability of once-daily dutogliptin 400mg, 200mg or placebo in patients with Type 2 diabetes mellitus. The trial was an international study and the intent to treat population consisted of 542 patients randomized in a 2:1:1 ratio (273 to the 400mg dutogliptin group, 137 to the 200mg dutogliptin group, and 132 to the placebo group).
• HbA1C - A form of hemoglobin that indicates the average plasma glucose concentration over a period of approximately 3 months.
- Fasting blood glucose (or fasting plasma glucose) - The concentration of glucose in the blood after an overnight fast.
- Peak postprandial blood glucose - The highest concentration of glucose in the blood measured after a standard mixed test meal with approximately 720 calories.
- Glucose AUC - An integrated measure of blood glucose in the standard mixed meal test over 2 hours.
About Type 2 Diabetes
Diabetes is characterized by high levels of blood glucose caused by insufficient action of insulin and inadequate production of glucose by the liver. It can lead to serious medical complications and death. In the United States, more than 10% of adults over the age of 40 have diagnosed or undiagnosed diabetes, and rates are anticipated to increase in the coming years. Type 2 diabetes is the predominant form of diabetes, accounting for 90 to 95% of diagnosed cases.
Dutogliptin is a once-daily inhibitor of the enzyme dipeptidyl peptidase-4 (DPP-4). These inhibitors prevent DPP-4 from breaking down the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), thereby increasing the levels of these hormones in the blood and potentially in the digestive tract as well. The incretins stimulate insulin production by the pancreatic beta cells and reduce glucagon production by the pancreas, both of which result in reduced blood glucose levels.
Dutogliptin is a highly-selective inhibitor of DPP-4 and possesses unique pharmacological properties including high water solubility, low cellular permeability and low volume of distribution. These features are desirable in the class of DPP-4 inhibitors because the DPP-4 enzyme is located extracellularly and circulates in soluble form in the blood. Dutogliptin does not undergo significant metabolism in humans and is renally excreted at a rate similar to the glomerular filtration rate.
Phenomix Corporation (www.phenomix.com) is a biopharmaceutical company focused on the discovery, development and commercialization of novel small molecule product candidates in significant therapeutic markets. The company's internally discovered lead product candidate, dutogliptin (PHX1149), is a DPP-4 inhibitor in Phase 3 development as an oral, once-daily treatment for Type 2 diabetes. The program is partnered with Chiesi Farmaceutici in Europe and other territories. Phenomix is located in San Diego, California.
(i) H.M.R. Pattzi et al. "Dutogliptin, a selective DPP-4 inhibitor, improves glycaemic control in patients with type 2 diabetes: a 12-week, double-blind, randomized, placebo-controlled, multicentre trial." Diabetes, Obesity and Metabolism 12: 348-355, 2010.