As part of our commitment to improving patient care in conditions that lack adequate treatments, Altus Pharmaceuticals® is actively investigating potential new drug therapies. We are currently conducting preclinical research and clinical trials to determine new ways of treating serious diseases, particularly for gastrointestinal and metabolic conditions. In order to help patients understand the importance of this research and determine if they can become involved in this effort, information is provided below on the clinical research process.

Developing a new drug is time consuming and expensive-averaging nearly 15 years and several hundred million dollars, according to the Pharmaceutical Research and Manufacturers of America (PhRMA). Before a drug can be approved for use in treating specific medical conditions, it must first be tested in the laboratory, in animals, and finally, in human beings.

What Is Preclinical Research?

Preclinical research is conducted by pharmaceutical companies early in the process of new drug development. This research takes place in both the laboratory and via animal studies to determine important information, including:

• The therapeutic effects the drug may have
• Potential side effects and toxicities
• Metabolism and clearance of the drug in the body

Good results in the preclinical or animal stage do not necessarily mean that similar results will be found when the drug is given to healthy volunteers or patients. For every 5000 drug compounds that enter preclinical testing in the United States, only about 5 will eventually be considered acceptable to test in humans. Of those final 5, only 1 drug may actually receive approval for use in patient care.

What Is a Clinical Trial?

Once the information is received from all preclinical studies, it is gathered into a proposal by the drug manufacturer, who files an investigational new drug (IND) application with the US Food and Drug Administration (FDA). Upon approval of this application, the manufacturer can begin testing the potential new product in humans via a series of clinical trials. Clinical trials are designed initially to test safety of the new drug. Subsequent trials continue to determine safety, but they are also designed to test whether the drug under study has therapeutic benefit and if so at what dose. These trials are categorized in phases.

What Phases Are Involved in Clinical Trials? Clinical trials take place in three phases. Each phase is designed to investigate different aspects of a new treatment. Patient participation is always voluntary. Patients may participate only if they agree to the potential risks of taking a new drug outlined in an informed consent form and meet specific medical criteria for entry in the study.

Phase I-Safety. The first phase in the clinical trial process aims to determine safety of a potential new drug. Researchers investigate what side effects the drug may cause, and how the drug breaks down in the body. Because little is known about the safety and dosing of the drug in humans at this stage, a relatively small number of patients/ healthy volunteers may be involved, from about 10 to 80 people. Phase I trials generally take an average of 18 months to complete. Researchers must immediately report any serious side effects to the FDA.

Phase II-Safety, dose-finding and effectiveness. In this phase, researchers continue to test the safety of the drug, but also begin to study the appropriate dose to reach a desired effect in treating the targeted medical condition. A phase II trial usually involves larger numbers of people (40 to several hundred) compared to phase I trials. In some cases, half of the volunteers may receive the study drug while the others receive a "placebo," or sugar pill, that has no therapeutic effect, so that the results can be compared. Multiple phase II trials may be conducted in order to study the drug's potential effect on different aspects of the disease or in different patient types. Several phase II trials may be required to determine efficacy of a given dose.

Phase III-Controlled trials for safety and efficacy. Phase III studies evaluate the efficacy of the drug in a greater number of patients than phase II trials, and may include hundreds to thousands of people. Adverse effects (side effects) continue to be evaluated to provide further documentation that the drug is safe. Phase III studies may include multiple "arms" that compare the drug to standard treatments to determine whether the drug is an improvement to, equal to, or less effective than currently available therapies. After all data are collected and analyzed from phase I through phase III trials, the drug manufacturer submits a new drug application (NDA) to the FDA. If enough information has been collected to document that the drug is both safe and effective in treating the specified condition, the FDA will grant approval and the drug will be made available for doctors to prescribe. The review process for the application, which typically is composed of as many as 100,000 pages, generally takes up to 12 months.