How Trials Work

Preclinical Studies  |   Investigational NDA  |   Clinical Trials  |   Orphan Indications

The U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) require that all potential drugs undergo a series of tests before entering the marketplace. These tests are designed to investigate the drug's safety and efficacy and become more complex as they progress through the various phases of preclinical and clinical development. The earliest preclinical tests might involve human cells grown in flasks. In later clinical trials, the drug is given to people characteristic of the patient demographic who have the disease or condition the drug is designed to treat. Below, you can learn how the drug development process works at Dyax. These descriptions are specific to the U.S. regulatory approval process.

From Millions of Molecules to One Drug
Dyax’s proprietary phage display technology is used to identify one single compound amongst millions that have ideal characteristics as a clinical drug candidate. Phage display first creates vast collections of molecules, called libraries, that might be of therapeutic use. Once scientists know what molecular characteristics are required of a drug candidate, a library can be searched for molecules meeting the requirements. This searching process is called screening. Because the libraries are very large, the screening process often turns up a group of related molecules within the library that could be good drug candidates. Through a process called selection, Dyax's scientists narrow this group to a few molecules that bind the target molecule the most tightly.

Dyax’s libraries of molecules include antibody, peptide, and small protein candidates.

Preclinical Studies
Next, drug candidates are tested in preclinical (non-human) systems for evidence of efficacy and safety. These may include experiments using animals (in vivo) or cultured human or animal cells (in vitro). Candidates that pass these rigorous preclinical tests move on to evaluation in animal studies and, ultimately, human clinical trials.

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Investigational New Drug Application
Before clinical trials can be initiated in the United States, the FDA must be informed about the drug and find that it is safe to allow the trials to proceed. Dyax first submits all known information about the potential drug to the FDA. This document is called an Investigational New Drug application, or IND, and its submission signifies the beginning of an on-going relationship with the FDA. Every planned clinical trial must be submitted to the FDA before subjects may be enrolled.

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Phase 1 Clinical Trials
Phase 1 trials include the first time a drug is tested in humans. Healthy volunteers are often the first to receive the drug. Phase 1 trials are small, with fewer than one hundred subjects. The primary objective of a Phase 1 trial is to determine if the drug is tolerable for human use. Phase 1 trials may also include pharmacokinetic studies, tests that measure how the drug distributes in the body over time.

Phase 2 Clinical Trials
Phase 2 trials are generally conducted in the population with the disease that the drug is intended to treat. These trials include more patients than Phase 1 trials and gather further information about the drug's safety, while also determining its efficacy. To discern if one dose or regimen is more beneficial than others, Phase 2 trials often include different dose groups. At this stage, trials may also be placebo-controlled.

Phase 3 Clinical Trials
Phase 3 trials are typically quite large, often including several hundred to several thousand patients to determine if the new drug has robust efficacy and acceptable safety for the diseased population. Phase 3 trials are designed to collect information to ultimately allow the drug’s sponsor to file for FDA approval.

Biologics License Application / New Drug Application
When the drug’s sponsor feels that enough information has been gathered about the drug to determine that it is safe and effective, the sponsor submits an informational package to the FDA along with detailed records of all preclinical and clinical studies, as well as information about the manufacture of the product. This submission to the FDA is called a Biologics License Application (BLA) or a New Drug Application (NDA). A team of FDA reviewers examines the information with the final goal of deciding whether the drug has a favorable risk-benefit ratio in the specified indication. This means that the drug’s benefits outweigh any risks or side-effects from the treatment.

Marketing
Once the FDA grants approval to a drug in a certain indication, that drug may be sold in the U.S. for the treatment of the specified condition in the specified patient population. Any other use is referred to as "off-label" and is not endorsed by the FDA.

Phase 4 (Postmarketing) Trials
Phase 4 trials may be initiated to monitor the long-term safety and effectiveness of a drug in its approved population and indication, or to test a new method of drug administration, new dosage form or new patient population. Alternatively, Phase 4 trials may investigate the drug's use in other indications.

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Orphan Indications
"Orphan" diseases or conditions are defined by the FDA as those that affect 200,000 or fewer Americans and by the EMEA as those that affect no more than five in every 10,000 persons in the European Union. The FDA and EMEA, may choose to streamline the approval process for drugs designed to serve a small and neglected patient population. A sponsor with such a drug can apply for orphan drug status with either or both agencies. If granted, orphan status can result in a modified clinical development program. This may include expedited FDA and EMEA reviews and a need to complete fewer or smaller clinical trials prior to approval.

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