Takeda defends Actos at FDA advisory committee

Takeda Global R&D (TGRD) has been defending the cardiovascular safety profile of its diabetes treatment Actos (pioglitazone) at a meeting of the FDA Endocrinologic and Metabolic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee.

The move parallels GlaxoSmithKline's (GSK's) presentation of longitudinal trial data to an FDA advisory panel to safeguard the future of its own diabetes drug, Avandia (roseglitazone). 

Japan-headquartered Takeda says that the most important safety data is contained within the PROactive (PROspective PioglitAzone Clinical Trial In MacroVascular Events) study, and like GSK, the company says that the most scientifically accurate way to determine the drug safety is through a prospective, long-term trial and not through meta-analyses.

The randomised, placebo-controlled outcomes PROactive study included 5,238 patients with type 2 diabetes with an established history of macrovascular disease. The patients were force titrated up to 45mg daily of Actos or a placebo. 

Results showed no difference in the number of macrovascular events between standard treatment and Actos, and standard treatment alone. Although there was no statistically significant difference between Actos and standard of care for the primary endpoint, there was no increase in mortality or total macrovascular events.

Actos' prescribing information was revised by the FDA to include the positive cardiovascular safety data and it is currently the only thiazolidinedione with safety data from a cardiovascular outcomes trial in its class. GSK will no doubt try to gain a similar label with its current longitudinal trial data presentation.

Dr Mehmood Khan, the president of TGRD, said: "The breadth and depth of Actos data, which encompasses more than 16,000 patients over the past 10 years, is consistent.  Short- and long-term studies, both prospective and observational, in both humans and animals, all have shown no evidence that Actos is associated with an increased risk of heart attack or stroke.î

On 31 July, Takeda reported a 5.1 per cent rise Q1 FY07 profit, but maintained its FY07 earnings at JPY 380bn (USD 3.2bn) due to the current FDA assessment of Actos' safety profile. Takeda said that Q1 FY07 net profit increased to rest at JPY 131bn (USD 1.1bn) on a 9.6 per cent rise in revenue from Q1 FY06. Actos racked up Q1 FY07 sales of JPY 106.6bn (USD 893.7m), up 26.9 per cent on Q1 FY06.

Takeda's shares increased three per cent in Q1 FY07, compared with a 0.6 per cent drop in the Tokyo pharmaceutical sub-index.