科途公开课：7分钟走近药物研发过程

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In drug research and development, the patient is the main focus. The mission of Novartis is to help the patient overcome a disease and improve their quality of life.

The drug development process is designed to ensure that innovative new medicines are effective, safe and available for patients in the shortest possible time. The first step in drug development is to discover the best targets for treating or preventing a disease. Targets are usually proteins in the patient’s body, which are associated with the disease or proteins in microorganisms causing a disease. The challenge is to identify which proteins are relevant, and more importantly, confirm their role in a disease. Increasingly, Novartis focuses on understanding cellular networks of proteins or pathways. A single protein may transmit messages to several other proteins, sometimes in multiple pathways affecting their function. Knowing how these pathways work and interact helps identify the most appropriate target for a drug. The pathway approach allows Novartis to better understand the mechanisms of a disease. This knowledge together with the desire to address unmet medical needs, determines the priorities in target discovery.

In drug discovery, several methods like high-throughput screening and computer based design are used to find chemical compounds or biologics that bind to the identified target. If a compound modulates the target in a way, that is expected to alter the disease. This so-called hit will be refined to improve its safety and effectiveness eventually becoming a drug candidate. Discovering and bringing one new drug to the market, typically takes an average of fourteen years of research and clinical development efforts, and cost around two billion US dollars. Of 10000 or more hits tested in early drug discovery, only one may eventually lead to a drug that reaches the market.

In the late preclinical stage, further experiments are conducted on the drug candidate. To ensure it is safe for patients and has the required pharmacokinetic properties, like appropriate absorption and metabolism by the human body. These experiments are executed with extraordinary diligence to minimize any risks to human test subjects. Animals play a critical role in the drug discovery process as well. Although much research and development can be done using various experiments or using computers, complex disease mechanisms can often only be understood through the use of animal studies. Also governments and regulatory authorities require that medicines be tested in animals before they are tested in humans. Novartis keeps this research as limited as possible had always ensures that animal research is scientifically acceptable according to current standards and regulations. For these reasons, Novartis continues to use animals in its quest to find innovative safe and life-saving medicines for patients. At the same time, Novartis is committed to refining, reducing and replacing the use of animals in research and upholding the highest standards in animal welfare.

Clinical trial programs consist of several phases. Each of which is focused on evaluating drug safety and effectiveness or efficacy. Information on ongoing clinical trials can be found at www.clinicaltrials.gov. In phase 1 of clinical trials, the drug is usually tested in healthy volunteers to determine its safety and pharmacokinetics. In phase 2, the drug is given to a group of about 100 to 250 patients with the disease. To re-evaluate its efficacy and to determine the optimal dose. In addition, the safety of the drug and its side effects are evaluated as these may be different in patients. Compared to the healthy volunteers tested in phase 1, Novartis also conduct trials called Proof-of-Concept or PoC trials, which are often a mix of phase 1 and phase 2 studies. A group of well-defined patients is treated with the drug candidate to provide an early indication whether it actually affects the target in the intended way or has a beneficial impact on the disease. These studies allow Novartis to rapidly invest resources on drug compounds which are effective and safe. This way the appropriate medicines can reach the patient’s faster. The data from phase 1 and phase 2 studies provide the scientific confidence necessary to continue the development of the compound in larger clinical trials. In phase 3 clinical trials, 1000 to 3000 or even more patients are recruited for research with the investigational drug. Phase 3 clinical trials are undertaken to confirm the effectiveness of the new drug, monitor side effects, compare it to establish treatments and gather additional information to allow the drug to be used safely. To bring a new medicine on the market, every new drug needs to be registered by the health authority. Data from all clinical trials are collected and compiled into a document called registration dossier. The registration dossier will include efficacy and safety data. To support the final intended use of the drug, the dossier is then customized for different regions and countries around the world to meet the requirements of health authorities. This is a crucial step to ensure that patients all over the globe can access the innovative medicines that have made it through the complex drug discovery and development process. Once the registration dossier is approved and the product is launched, several activities will continue, like drug safety monitoring which is mandatory. Post authorization safety updates, annual reports and any additional information required by the health authority must be provided at the find intervals as long as the drug remains on the market. Often, phase 4 clinical trials are initiated to gather additional data not collected in the phase 3 program. This may include efficacy, safety, additional benefit and risk information as well as pharmacal economic data. Our mission is to provide safe and effective treatments that benefit patients and improve the quality of their lives.