Biopharmaceutical company Amicus Therapeutics presented updated and encouraging results for its experimental Pompe disease (acid maltase deficiency) compound AT2220 this week at the 17th International Congress of the World Muscle Society in Perth, Australia.
AT2220, also known as duvoglustat HCl, is a pharmacological chaperone that is believed to help stabilize the therapeutic enzyme given to treat Pompe disease and thereby enhance the effectiveness of enzyme replacement therapy for this metabolic muscle disorder. The drug may prevent the enzyme from unfolding.
The new update includes a report on trial participants receiving AT2220 at three different dosages, and on an MDA-supported study of the effects of the drug on human immune system cells in laboratory dishes. The phase 2 study is ongoing but is now closed to new participants.
Enzyme replacement therapy (ERT) for Pompe disease is available in the United States and several other countries under the brand names Myozyme and Lumizyme. The therapeutic enzyme used in ERT is known as acid maltase or acid-alpha glucisodase (GAA), and is given by infusion.
ERT has improved the lives of children and adults with Pompe disease. However, the benefits vary among individuals, a phenomenon not entirely understood. One factor in the effectiveness of ERT may be the immune system's tolerance of the therapy, which potentially can be improved by keeping the therapeutic enzyme properly folded. In addition, enhancing the effectiveness of ERT could potentially reduce the dosages needed and the cost of treatment.
Interim results for AT2220 trial
So far, one oral dose of AT2220 has been given to 16 trial participants with Pompe disease, who were divided into three groups. Group 1 received a 50-milligram dose immediately prior to an ERT infusion; group 2 received 100 milligrams; and group 3 received 250 milligrams.
Dosage group 4 is slated to receive a 600-milligram dose. Results are expected during the fourth quarter of 2012.
In its Oct. 11 press release, Amicus said this about its phase 2 study of AT2220 plus ERT:
In addition to increasing enzyme activity, AT2220 also appears to reduce the chance that ERT will cause an immune response that interferes with the therapy. The company's hypothesis is that, by stabilizing the folded and active form of the GAA enzyme, AT2220 may mitigate an unwanted immune response to the enzyme.
The tendency for the immune system to mount a response against ERT in Pompe disease has been an ongoing challenge to the success of the treatment.
In parallel with the clinical trial of AT2220, Amicus has been conducting an MDA-supported study of the effects of ERT alone and ERT plus AT2220 on human T cells in laboratory containers. T cells are part of the immune system.
To see whether AT2220 can reduce the immune response to ERT, Amicus studied blood samples from 50 healthy donors to see whether their T cells would be less responsive to ERT if they were also exposed to AT2220.
In the Oct. 11 press release, the company said:
To learn more about the phase 2 trial, as well as the history of enzyme replacement in Pompe disease, read: