First in Class Drug for Diabetes enters Phase 2b Clinical Testing. Metabasis announced that MB07803 which is designed to regulate glucose production in the liver by inhibiting an enzyme known as fructose 1,6- bisphosphatase (FBPase), a key component of the gluconeogenesis pathway is starting clinical trials. This means yet another class of diabetes drugs could be coming around the corner soon.
Metabasis Therapeutics, Inc. (Nasdaq: MBRX) announced today that it has initiated a Phase 2a clinical trial for MB07803, a product candidate being studied as a treatment for patients with type 2 diabetes. MB07803 is the second member of a new class of drugs discovered by Metabasis that inhibit a metabolic pathway in the liver called gluconeogenesis, which is responsible for the excessive production of glucose by patients with type 2 diabetes.
The Phase 2a proof of concept study will be a randomized, double-blind, placebo-controlled, 28-day trial involving approximately 60 patients with type 2 diabetes. One group will receive a placebo, and the other four groups will receive different doses of MB07803 administered once daily. The study will evaluate the change from baseline in fasting plasma glucose levels of MB07803-treated patients relative to placebo-treated patients after 28 days of therapy.
Four Phase 1 clinical trials for MB07803 were initiated and completed during 2006. While the Company is still evaluating the data in these recently completed Phase 1 studies, the product candidate was found to be safe and well tolerated. No serious adverse events were seen, all adverse events were mild and resolved, and there were no withdrawals due to adverse events.
MB07803 is a second generation compound that Metabasis internally discovered that inhibits the gluconeogenesis pathway. The first product candidate in this category, CS-917, was also discovered by Metabasis. While MB07803 is structurally different from CS-917 and may have certain advantages, both compounds are designed to regulate glucose production in the liver by inhibiting an enzyme known as fructose 1,6- bisphosphatase (FBPase), a key component of the gluconeogenesis pathway.
While Metabasis is independently developing MB07803, CS-917 is being developed by Metabasis’ partner, Daiichi Sankyo. Daiichi Sankyo has completed two successful Phase 2a studies and is currently evaluating CS-917 in a Phase 2b clinical trial initiated in February 2006. This is a multi-center, randomized, double-blind, placebo-controlled clinical trial of CS-917 given orally as a single agent, for the treatment of patients with type 2 diabetes. The clinical trial is designed to evaluate safety and tolerability after three months of dosing of CS-917, as well as its effect on blood levels of HbA1c, an important measure of long-term glucose control in patients with type 2 diabetes. Enrollment in the trial was recently completed with a total of 392 patients having been enrolled in the U.S. If successful, in addition to potentially providing further evidence of safety and efficacy, this clinical trial could support selection of a dose for Phase 3 clinical trials.
Dr. Mark Erion, executive vice president of research and development and chief scientific officer said, “With an estimated 180 million people worldwide with type 2 diabetes and with incidence continuing to grow, new treatment approaches are urgently needed as current therapies often achieve only modest reduction in glucose levels in many patients. The specific and direct inhibition of gluconeogenesis represents a potential new approach for treating type 2 diabetes. The clinical success achieved to date with CS-917 by our partner increases our confidence in the potential of MB07803. If approved for use, CS-917 and MB07803 could prove to be an important new class of candidates that have the potential to be an effective approach for treating this chronic, life-threatening disease.”
“The significance to Metabasis of the continuing clinical development of MB07803 goes beyond being the second of what could prove to be a major new class of drugs for treating diabetes,” stated Dr. Paul Laikind, president and chief executive officer. “We believe that if the promise of this potential new class of drugs is fully realized upon further clinical evaluation and both products are ultimately approved for use, both could find wide usage. But equally important, this milestone is another step in our progress toward building a leading, commercially successful biopharmaceutical company, discovering, developing and commercializing innovative therapies for chronic diseases. By advancing our clinical pipeline, which includes three metabolic disease product candidates, along with two product candidates for primary liver cancer and hepatitis B respectively, we get closer to realizing this goal.”