Making new drugs and bringing them to market is a lengthy process than can take over a decade to complete, but why does it so long and what does it actually involve? What are the main steps and considerations? How do you go from a an interesting molecule in the lab to a drug that can be given to patients in the clinic?
DRUG DEVELOPMENT
There are 3 main parts that apply to drug development in most disease areas, here we use drugs developed to treat cancer as an example:
1. Pre-clinical testing: Here we test molecules in the lab to see if they are active against the intended target and if by hitting the target (and hopefully not much else) they can also kill or stop the growth of cancer cells (i.e. produce the expected effect). If all of this can be demonstrated, investigations move then to test drug activity against tumour models (in mice). If the drug shows activity in step 1 (pre-clinical testing), it is said to have achieved pre-clinical proof of concept and is then able to move to the next stage.
2. Safety and product quality: Here we assess the potential safety/toxicity profile of the drug in addition to its metabolism and clearance from the body. This usually involves investigating several doses of the drug in various models and animal species to understand how a drug is processed in the body and whether it causes any undesirable effects on e.g. organ function, body weight etc. This assessment informs whether a drug can move to the next stage in the process, and be tested in humans. This work also helps guide the starting dose in human trials. In parallel, chemistry and manufacturing work is carried out to ensure the drug product can be produced to a high quality and that it is safe and stable and that it is made up with the most suitable formulation. Once all of this is completed, human testing can start (also known as first in human trials).
3. Clinical testing: This involves 3 main stages:
Phase 1 trials: These will evaluate small numbers of patients (tens of patients) and multiple increasing doses (dose escalation) to determine if a drug is safe in humans, and if so, what dose should be selected for more evaluation (dose expansion)
Phase 2 trials: Here we assess if the a drug has activity against a particular disease condition (in ca. 100 patients) – in cancer this means whether the treatment leads to disease control or even tumour size reduction.
Phase 3 trials: These are the biggest trials (hundreds of patients) and are usually randomised against the currently available treatment in order to test how the activity of the new drug compares to the activity of the established standard treatment. Larger Phase 2 or Phase 3 trials can be done as basket or umbrella trials, where groups of patients within several disease indications are enrolled for treatment with a single drug (basket design) and in other cases, several drugs are evaluated in the same indication (umbrella design)
If the new drug shows greater benefit and it overall side effect profile is satisfactory (manageable) then the trial is said to be successful and the drug can be submitted to the heal authorities for regulatory approval
DRUG APPROVAL AND MARKETING
Once a new drug is approved, it can in theory be prescribed to patients, however this is not as straight forward as that since someone needs to pay for it. This is known as reimbursement, or market access, and in many countries requires negotiation and discussion with payers around the benefits, value and cost effectiveness of the new treatment.
After drug approval marketing, monitoring of benefit/risk profile of the new treatment continues in the real world setting (routine clinical practice). Life cycle management activities may involve assessing activity in new disease areas, whether combination treatment with another drug can improve efficacy of the current treatment, whether a new formulation can ease the way a drug is given etc….all of this will require going back in the cycle of testing safety/efficacy in the lab then the clinic etc etc…
