Type 2 diabetes mellitus is an epidemic not only in the United States but worldwide. While several drug treatments are available, federal health agencies, physicians and patient advocacy groups support the development of new agents that can safely control high blood sugar levels and help prevent and treat diabetes.
Companies wishing to introduce a new drug therapy into the U.S. market must obtain Food and Drug Administration (FDA) approval. It's the company's responsibility to test the drug and provide evidence that it's safe and effective. The FDA does not test drugs. The agency's Office of Testing and Research conducts limited research in the areas of safety, quality and effectiveness.
Applications are reviewed by panels of experts that may include staff and consulting chemists, pharmacologists, physicians, statisticians, and other scientists. Drugs for the treatment of diabetes are reviewed by the FDA's Endocrinologic & Metabolic Drugs Advisory Committee.
Investigational New Drug ApplicationIf the sponsor's initial laboratory studies provide promising data, the developer may submit an Investigational New Drug (IND) application to the FDA's Center for Drug Evaluation and Research (CDER). There are three types of IND applications:
- Investigator - Submitted by a physician who oversees the investigation
- Emergency Use - FDA authorized use of an experimental drug in an emergency situation. This application allows an exemption for patients that do not meet criteria for an existing study protocol or it may be used when there is no existing approved study protocol.
- Treatment - Submitted for experimental drugs showing promise in clinical testing for serious or life-threatening conditions while the final clinical work is conducted and the FDA review takes place.
The application must include:
- Manufacturing specifications
- Stability and bioavailablility, or the amount of drug that is absorbed by dose
- Method of analysis for each form of dosage
- Packaging and labeling for both physician and consumer
- Results of all toxicological studies
Clinical Trials
The drug sponsor may begin their clinical trials on human subjects 30 days after submitting the IND application. If the FDA finds a problem with the proposed trial during the wait period it may put it on hold. The FDA may also interrupt a clinical trial if problems occur during the study. Clinical trials are done in phases.
Phase I trials are the first human tests of new drugs or therapies. They generally enroll a very small number of volunteers and their purpose is to determine optimum dosage and observe possible side effects.
Phase II trials involve larger numbers of volunteers. Their purpose is to observe how well the therapy works in a small number of patients.
Phase III trials may involve hundreds or thousands of patient volunteers. The objective at this phase is to test the effectiveness of the treatment. In some cases, this is the stage at which new therapies are compared with standard treatments using randomization, control groups and placebos.
The drug sponsor analyzes the clinical trials data. If there's enough evidence that the drug meets the FDA's requirements for safety and effectiveness for marketing approval the trial results may be submitted for FDA review.
Some drugs are taken through numerous clinical trials. For example, Onglyza (saxagliptin), a tablet taken once daily to treat Type 2 diabetes in adults, underwent eight clinical trials prior to gaining approval in 2009.
Recommendations for New Diabetes Therapies
Because patients with diabetes have a higher risk for developing cardiovascular diseases, the FDA encourages sponsors to contact the Center for Drug Evaluation and Research during clinical trial planning stages to incorporate methods for minimizing the risk of cardiovascular side effects and also to monitor stroke, heart attack and other cardiovascular events taking place during phase 2 and phase 3 trials. Drug developers should have methods in place that can demonstrate after a trial that the new anti-diabetic therapy is not associated with an increased risk for cardiovascular disease.
Patent Protection During Drug Development
Most new drugs and devices are under patent protection during development. The patent protects the sponsor's investment in the drug's development by giving them the sole right to sell the drug while the patent is in effect. After patents or other exclusivity periods on brand-name drugs expire, the manufacturers can apply to the FDA to sell generic versions.
Fast Track Approvals
New therapies for some serious diseases, including diabetes, are eligible for the FDA's "fast track" approval process. If the therapy has a strong potential to fill an unmet need in treatment or offers potential advantages over existing options, the therapy may be eligible for help with development and expedited review.
