BioWorld International Correspondent
Rheoscience A/S and its development partner Dr. Reddy's Laboratories Ltd., moved balaglitazone, a partial agonist of peroxisome proliferator-activated receptor (PPAR) gamma, into a Phase III clinical trial in patients with Type II diabetes.
The 500-patient, six-month study is comparing the efficacy of two different doses (10 mg and 20 mg) of balaglitazone, a member of the thiazolidinedione class of insulin sensitizers, with a 45mg daily dose of Actos (pioglitazone), marketed by Takeda Pharmaceutical Co., of Osaka, Japan. The trial also includes a placebo arm. All patients recruited into the study will be on stable insulin therapy. The primary endpoint will be reduction of blood glucose levels, as measured by levels of glycated hemoglobin, and the study is powered to demonstrate non-inferiority of balaglitazone as compared with Actos.
The trial, in which the first patient has been dosed, began just days after another thiazolidinedione, Avandia (rosiglitazone maleate), marketed by London-based GlaxoSmithKline plc, survived an FDA advisory committee vote, called in the wake of a meta-analysis indicating it posed an increased risk of myocardial infarction.
Copenhagen, Denmark-based Rheoscience took on global development responsibility for balaglitazone through an agreement it entered with Hyderabad, India-based Dr. Reddy's in 2005. It holds commercialization rights to the compound in the European Union and China. The latter firm retains rights to other territories.
The company hopes to obtain data that would differentiate balaglitazone from Actos, which racked up around US$900 million in sales in its fiscal first quarter, ended June 30, and Avandia, which, along with its related combination therapies Avandamet and Avandaryl, took in US$692 million in the same period.
Balaglitazone's partial agonistic action could be the key, as it does not appear to activate expression of all of the genes that are affected by Actos and Avandia. "It has the same effect on glycemic control, but is has a lesser impact on some of the side effects associated with this class," Rheoscience CEO Philip Larsen told BioWorld International. Foremost among these are fluid retention, which can lead to or exacerbate heart failure, and weight gain.
Phase II monotherapy studies indicate that it is "equi-efficacious to the maximum allowed dose of Actos," Larsen said. The Phase III program will comprise five to six studies involving different combination therapies, as well as a long-term safety study. The company has not yet finalized its filing strategy, Larsen said, since does not contemplate a new drug application until after 2009.
For the same reason, it is in no hurry to find a commercial partner for the product. "We'd really like to see what potential the drug has before we enter a deal," he said. It has high hopes for the product, however. "I would be a wimp if I said we would only get five percent of the market," he said.
Hayward, Calif.-based Metabolex, Inc., and New Brunswick, N.J.-based Johnson & Johnson, recently moved another PPAR gamma agonist, a non-thiazolidinedione called MBX-102 (also known as JNJ 39659100), into a Phase II/III clinical trial in type II diabetes.
Balaglitazone was previously the subject of a development agreement between Dr. Reddy's and another Danish firm, Ballerup-based Novo Nordisk A/S. However, the latter discontinued development in 2004, citing preclinical data suggesting it offered insufficient competitive advantage compared with existing therapies.
Rheoscience was spun out of the Center for Clinical and Basic Research A/S, a private research foundation based in Ballerup, in 2002. It has been funded to date by its owners, private investors Claus Christiansen and Bo Krøll.