Developing Medication

Scientists and doctors search for better treatment options for hepatitis patients.© German Liver Foundation

© Deutsche Leberstiftung

Developing a new medication usually takes more than ten years. Out of the several thousand substances investigated in basic and pre-clinical research, only one or two candidates are approved by regulatory authorities at the end of this long journey. The DZIF is involved in many development projects right from the start. Its remit is wide, including identifying new targets for anti-infectives and vaccines as well as discovering new active agents and biomarkers, pre-clinical research as well as phase I and II clinical trials. After phase II at the latest, the DZIF aims to collaborate with the pharmaceutical industry to further drive product development.

The development phases in translational medicine

Focusing on the patient

First, there is a medical need. Are there diseases that cannot be easily cured? Could vaccines prevent the disease? Do those affected need new medication because current medication is no longer effective? Antibiotic resistance is a current problem and an important area of research at the DZIF.

Finding new targets and developing drug candidates

In many cases, the search for a new medication begins with precisely analysing the development of the disease. At what point could active agents intervene and affect the process to the benefit of the patient? It is often molecules such as enzymes or receptors that are potential targets of medication. After, the development team looks for suitable drug candidates by screening substance libraries as well as specifically synthesizing substances that could bind to the target.
In 2015, the DZIF was able to discover two antibiotic substances with new mechanisms using screening - cystobactamid and teixobactin. The next important step is to improve the substances for further trials.

Preclinical development: Cell cultures and animal models

Before the drug candidates can be tested on humans in any form, their efficacy and tolerability must be proven in cell cultures and animals. If the substance proves to be toxic or extremely intolerable during these laboratory tests, it is very unlikely to be further developed. If the pre-clinical phase is successful, development can continue.
For example, at the DZIF a vaccine candidate for the MERS coronavirus and a new active agent for tuberculosis successfully passed the pre-clinical trials so that the next phase has begun or is in preparation.

Phase I trials: Trial using a small number of healthy participants

The first clinical trial with a small number of healthy adults first tests the tolerability and safety of the drug candidate. How does the substance react in the body? What dose can be administered without any side effects and is the medication safe? For these trials, the active agent must be produced under GMP conditions. This means it is strictly controlled according to Good Manufacturing Practice guidelines. 60 to 80 test subjects generally participate in these trials.
A good example of a successful phase I trial at the DZIF is the development of an Ebola vaccine, which was tested at the same time at four locations in Europe, one of which was the DZIF site Hamburg-Lübeck-Borstel-Riems. The phase I trial was successful and initiated the further development to a vaccine, which is now being continued by a pharmaceutical company.

Phase II trials: Trial using a small number of ill participants

Tolerability and efficacy are tested, and now phases IIa and IIb begin for investigating the efficacy, tolerability and posology. First, the pharmaceutical form is developed. Should the active agent be administered as a tablet, an ointment or a solution for injection? Phase IIa trials mainly investigate proof of concept, while phase IIb trials focus on finding the correct dosage. Phase II trials generally include 100 to 500 ill adults. Participation is voluntary, and all clinical trials must be approved by the responsible national authorities and the ethics commission before they begin.
An active agent for hepatitis B - myrcludex B - which was co-developed at the DZIF has been tested in a phase IIa trial and is a promising candidate for further product development.

Phase III trials: Trial using a large number of ill participants

During the last phase of possible approval as a medication, doctors test it on thousands of patients to see whether efficacy and safety can be confirmed on many different patients. Interactions with other medicinal products are also tested during this phase. Phase II and phase III trials are typically so-called controlled trials: One group of patients receives the new medication, the other group receive the previous standard preparation.