A small, Phase 2 clinical trial led by a team of researchers at Indiana University is evaluating the former psoriasis drug alefacept as a potential new therapeutic for Type 1 diabetes. Astellas Pharma US, a subsidiary of Tokyo-based Astellas Phama Inc, previously marketed Alefacept under the brand name “Amervive”. In March 2006, Astellas bought the worldwide rights to market Amevive from Biogen Idec Inc. (BIIB) . In November 2011, the company voluntarily discontinued promotion, manufacturing and sales of Amervive, citing business needs as the reason and not any specific safety issues of FDA mandates in the decision.
In 2003, Amevive was the first biologic approved by the FDA for the treatment of moderate to severe chronic plaque psoriasis in adults who are candidates for systemic therapy or phototherapy. It garnered regulatory approval in the U.S., Canada, Israel, Switzerland and Australia. The European Medicines Agency never approved the drug.
As often happens, old drugs don’t die, they get recycled. The researchers said that alefacept could work better against Type 1 diabetes because it protects the immune system and preserves insulin secretion. Further, alefacept mechanism of action in the treatment of psoriasis includes attacking specific T cells, namely effector memory (Tem) cells and central memory (Tcm) cells. In diabetes, these cells are known to attack insulin-producing cells in the pancreas.
In the clinical trial, which began in March 2011 when Amervive was still on the market, 49 individuals that were newly diagnosed with Type 1 diabetes were studied across 14 U.S. centers. The trial originally planned to have 66 subjects enrolled, but Astellas pulling the drug limited enrollment to 49. 33 patients were administered weekly injections of alefacept for 12 weeks, followed by a 12-week break and then 12 more weeks of treatment. The other 16 patients received a placebo on the same schedule.
The trial failed to hit its primary endpoint of a demonstrating a statistically significant change from baseline in mean 2 h C-peptide area under the curve (AUC) at 12 months. Essentially, the researchers were looking to see an effect in how well the pancreas secreted insulin two hours after eating. However, researchers did note that two important secondary endpoints were met with a statistically significant change in insulin secretion four hours after eating and a reduction in hypoglycemic events (low blood sugar), a common problem in Type 1 diabetes patients. After 12 months, insulin use was higher in the placebo group than the treatment group, suggesting that the drug helped the body’s ability to make its own insulin. Hypoglycemic events in the treatment group had a mean of 10.9 events per person per year, compared to 17.3 events in the control arm.
A final secondary endpoint measuring changes in HbA1c concentrations at 12 months showed no significant difference between the groups.
No serious adverse events were reported.
The US National Institutes of Health and the Juvenile Diabetes Research Foundation provided funding for the trial. The trial is continuing with additional measurements to be collected at 18 and 24 months.
Type 1 is the lesser diagnosed of the three types of diabetes. Type 2 is the frontrunner, with about 95 percent of all cases falling into this category. Diabetes develops when the body doesn’t make enough insulin or inefficiently uses insulin, allowing glucose to accumulate in the blood, rather than being absorbed by cells, eventually damaging blood vessels and nerves and leading to other complications, such as blindness, kidney failure or even comas.
It doesn’t look like alefacept is going to be heralded as a potential “cure” for Type 1 diabetes, but there is the possibility of helping control the disease in newly diagnosed patients in the future. Of course, additional research with larger enrollments is required.
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