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Clinical Programs
Lexicon has advanced four drug candidates into human clinical trials with an additional candidate in preclinical development and a pipeline of additional candidates in various stages of preclinical research. All of our drug targets have been identified internally as part of our Genome5000™ program. Our lead programs include:
- LX6171 in Phase 2 clinical trials for the treatment of cognitive disorders,
- LX1031 has completed Phase 1 clinical trials for irritable bowel syndrome,
- LX2931 in Phase 1 clinical trials for rheumatoid arthritis, and
- LX1032 in Phase 1 clinical trials for carcinoid syndrome (Fast Track status).
Our 10TO10 goal is to advance 10 drug candidates into human clinical trials by the end of 2010. We believe that our systematic, genetics-driven approach to drug discovery will enable us to substantially expand our clinical pipeline. Our drug pipeline consists of small molecule and biologic drug candidates, a fact that diversifies our approach to drug discovery and development.
Clinical Trials Process
When a drug candidate has completed formal preclinical studies, a regulatory filing must be made with an appropriate regulatory agency in order to initiate human clinical trials. In the United States, an Investigational New Drug (IND) application must be filed with the FDA before initiating human clinical trials. The main purpose of an IND is to provide data to the FDA showing that a new drug candidate demonstrates the required safety profile for initial testing in humans. The IND is not an application for marketing approval.
Phase 1 Clinical Trials
Phase 1 clinical trials are the first trials in which a new drug candidate is tested in human subjects. Phase 1 clinical trials are typically designed to assess the safety, tolerability, and pharmacokinetics of a drug. Usually Phase 1 clinical trials are conducted in a small group of healthy volunteers, although actual patients with disease may be used in certain circumstances. In a typical Phase 1 study design, subjects are administered a single dose of the new drug and observed over a period of time. If the subjects do not exhibit any adverse side effects, and the pharmacokinetic data is in line with predicted safety values, the dose is escalated until intolerable side effects appear or pre-calculated pharmacokinetic safety levels are reached. At this point, the drug is said to have reached the maximum tolerated dose (MTD). This classic study design is known as a single-ascending dose study. Following the single-ascending dose study, multiple-ascending dose studies are conducted to better understand the pharmacokinetics and safety profile of multiple doses of the drug. In these studies, a group of subjects receives multiple doses of the drug. At various times, blood samples and other fluids are collected and analyzed to understand how the drug is processed within the body. The dose is subsequently escalated up to a predetermined level.
Phase 2 Clinical Trials
Once the initial safety profile of the drug has been established in Phase 1 clinical trials, Phase 2 clinical trials are conducted to assess how well the drug works in patients with a particular disease. Phase 2 clinical trials include a larger group of patients and typically test different dose levels. Safety assessments are also continued. Phase 2 clinical trials are usually divided into Phase 2a and Phase 2b trials. Phase 2a is specifically designed to assess dosing requirements, whereas Phase 2b is specifically designed to study the efficacy of the drug. Some trials combine Phase 1 and Phase 2, and test both efficacy and tolerability. Most Phase 2 trials are designed as randomized clinical trials, where some patients receive the drug and others receive placebo.
Phase 3 Clinical Trials
Phase 3 clinical trials are randomized, multi-center trials to definitively assess how effective a drug is to treat a particular disease. Phase 3 clinical trials are the most expensive trials to design and run because of the large number of patients studied and comparatively long duration, especially in therapies for chronic medical conditions. Certain Phase 3 trials, often called “registrational” or “pivotal” trials will be submitted to support initial approval of the drug for marketing. Commonly, other Phase 3 clinical trials will continue while the regulatory submission for marketing authorization is pending at the appropriate regulatory agency. This allows patients to continue to receive possibly lifesaving drugs until the new drug is marketed. Phase 3 clinical trials may also continue in order to assess additional types of patients or diseases amenable to treatment with the drug to obtain additional safety data, or to support marketing claims for the drug.
Marketing Approval
Once a drug has proved satisfactory after Phase 3 clinical trials, the trial results are usually combined into a large document containing a comprehensive description of the methods and results of human and animal studies, manufacturing procedures, formulation details and shelf life. This collection of information makes up the "regulatory submission" that is provided for review to the appropriate regulatory authorities. They will review the regulatory submission and may authorize marketing approval. In some cases, regulatory authorities may ask for additional clinical data to be obtained in subsequent clinical trials. Once the regulatory authority has approved the drug, it may be actively marketed in the appropriate territory. Additional regulatory filings must be made in each country where marketing approval is sought.
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