Showing Signs of Success
Dr. Barthlemy points to recent registrations of two peptide drugs as "good news for peptide APIs." Earlier this year, Amylin Pharmaceuticals (San Diego) and Eli Lilly (Indianapolis) announced FDA approval of Byetta (exenatide) for injection, an adjunctive therapy intended to improve blood sugar control in patients with type 2 diabetes who have not achieved adequate control with the use of metformin and/or sulfonylurea.
Exenatide is the first approved compound from the new drug class of incretin mimetics. These compounds stimulate insulin secretion and restore the body's ability to respond to increased blood sugar levels, which is compromised in type 2 diabetes. Amylin formulated Byetta for use as a fixed-dose, subcutaneous self-injectable given before the morning and evening meals.
The FDA also granted approval to Amylin's drug Symlin, or injectable pramlintide, a synthetic analog of human amylin for use in combination with insulin to treat diabetes. Amylin is a hormone that helps regulate appetite and food intake.
In recent weeks, the company presented data from a 16-week Phase II clinical study of pramlintide for the treatment of obesity. The company reported significant, progressive weight loss of 3.6% with pramlintide compared to placebo and no evidence of a plateau effect at 16 weeks. Amylin has initiated a Phase II dose-ranging study in 400 obese subjects.
With plans under way to expand manufacturing capacity at both its Torrance, CA, and Malmo, Sweden, facilities, PolyPeptide Laboratories (Hillerod, Denmark) is preparing for the increased demand that will result largely from Big Pharma's renewed interest in peptides as viable therapeutic candidates, according to Jane Salik, Ph.D., president of PolyPeptide's U.S. operations.
Not only is pharma developing peptide products they have acquired through partnerships, but they are also "bringing us projects from their own discovery," notes Dr. Salik.
And even though it was dogma in the industry only 510 years ago that longer peptides were too expensive to produce as therapeutics, we are seeing "some larger peptides now being considered quite seriously as therapeutic candidates," she adds.
Dr. Salik attributes this trend to improvements in chemistry, purification, and large-scale synthesis strategies and equipment, as well as, in part, to the example set by the Trimeris/Roche drug enfuvirtide, or Fuzeon, a long peptide that requires a complex synthesis process and is being produced in amounts exceeding 3,500 kg/year.
Fuzeon has not only established a benchmark for the production of longer, more complex peptide drugs, but it has also demonstrated success in navigating the regulatory approval process.
Dr. Salik would like to see more definitive regulatory guidelines established for peptide molecules, in particular with regard to impurities. Looking ahead, though, she foresees no regulatory issues facing peptide therapeutics as a whole and believes that current separation and purification technologies are quite adequate and readily scalable.
However, she suggests the need to explore new methods for isolating peptide products, as lyophilization will likely become a rate-limiting factor in therapeutic peptide manufacturing.
With its issuance of a guidance encouraging manufacturers of cGMP peptides to adopt Process Analytical Technology (PAT), the FDA emphasized the need for a more scientific and analytical approach to the art of synthesizing peptide drugs.