Phase III: Large-Scale Clinical Trials
Upon successful completion of Phase II, the drug enters Phase III clinical trials, involving a significantly larger and more diverse patient population. These trials aim to confirm the drug's efficacy, monitor side effects, and compare its performance to existing treatments or a placebo. The data collected in this phase provide the basis for regulatory submissions to health authorities. Phase III trials are the longest, often lasting several years due to the need for extensive patient enrollment and data collection.
After a drugs safety and efficacy is proven, the drug sponsor submits a New Drug Application (NDA) to regulatory agencies such as the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA) or the Swiss Agency for Therapeutic Products (Swissmedic). Regulatory authorities thoroughly review the accumulated data before deciding whether to approve the drug for market entry. Regulatory review can take several months to years, depending on the complexity of the application and the need for additional information.
Phase IV: Post-Market Surveillance
Once a drug receives regulatory approval, it enters Phase IV, also known as post-market surveillance. Now, the drug is on the market and available outside clinical trials. According to the Swissmedic, it takes on average ten to twelve years for a product to reach this stage.
Phase IV includes ongoing monitoring of the drug's safety and effectiveness in this large patient population. Long-term data collection helps identify rare side effects and ensures the drug's continued safety and efficacy.
The phases of drug development
Repurposing of approved drugs and accelerated approval
Besides the traditional pathway of drug development, a process called drug repurposing or repositioning describes exploring already approved drugs for the treatment of a different disease or symptom. In this case, the safety profiles and mechanisms of action are already known, and the drug can be explored from a later phase.
One notable example is temelimab, originally approved for the treatment of autoimmune diseases such as rheumatoid arthritis. Researchers have begun exploring its potential in other conditions, including Long COVID. By repurposing drugs like temelimab, researchers can expedite the development process and potentially bring new treatment options to patients faster and more cost-effectively.
Under special conditions, a drug can be registered for accelerated approval after Phase II. This deviation from standard processes has been observed in several cancer drugs who performed so well in Phase II that access to the market was granted early.
Another exception can be made for orphan drugs: drugs for rare diseases where no valid treatment options are available. Orphan drugs help such a small patient population that it wouldn’t be financially worthwhile for pharmaceutical companies to go through the intense process of approval before catering to a very small market. Rather than have no treatment for these rare diseases, approval can be sped up in these cases.
Biomarkers versus druggable targets – what did the Zurich study find?
In the realm of drug development, it's essential to differentiate between druggable targets and biomarkers. Druggable targets are specific molecules, proteins, or biological processes that can be modulated by drugs to treat a particular disease. These targets play a pivotal role in the efficacy of potential therapies and serve as the focal point for drug discovery efforts.
On the other hand, biomarkers are measurable indicators that reflect normal biological processes, disease progression, or response to treatment. While some biomarkers may also serve as druggable targets, their primary function is to aid in disease diagnosis, prognosis, and monitoring treatment response.
The recently published study from Zurich identified biomarkers. They observed that parts of the immune system (complement system) and blood clotting worked differently in Long COVID patients compared to healthy controls. Blood clotting and the complement system are very important bodily functions that could be difficult to target with a drug without major side effects. However, they are promising biomarkers that could help in diagnosing Long COVID and also reflect, what a serious whole-body disease Long COVID is.
One of the main concerns of biomarkers is specificity. In the example of Long COVID: is the biomarker always a sign for Long COVID and is it a sign only for Long COVID? If not, the outcome would not be reliable. We would ask: does the patient not have Long COVID or did the biomarker not work? Or: does the patient have Long COVID, or another disease where the marker looks the same?
In summary, all drugs and biomarkers need to be efficient, reliable, and safe. This is why their development takes time. Nonetheless, scientific discoveries continue to drive innovation in drug and diagnostic development, offering hope for us at Altea and our Altea Community.
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