Research, fail, keep on researching
Bringing a single drug to market involves studying 10,000 different compounds. Of these, only about 10 are clinically analysed in greater detail until one of them can be processed into an effective drug.
But how do research companies know which direction to take in the first place? By narrowing down the possible fields of research with a host of questions: Which are the diseases creating a need for new medicines? Are there any existing drugs with side effects that should be reduced? Do we now know more about a particular disease that would justify further research?
Once a specific field of research has been defined, scientists from a range of disciplines such as chemistry, biology, medicine and pharmacy come on board and help with small individual steps to ensure that a drug can make steady progress along the chain of research. Until approval is hopefully achieved.
The reason for such a lengthy process is that researchers do all they can to minimise side effects and ensure the product’s efficacy. Only when a substance has passed all the required preclinical testing can it also be tested on humans.
On average, scientists spend 12 years meticulously researching a single drug with patience and perseverance. They perform experiment after experiment, only to start all over again just before reaching the finish line. Between 1998 and 2017, for example, there were 150 unsuccessful attempts to develop an Alzheimer’s drug – and ultimately just four drugs received approval in this therapeutic area.
In their work, therefore, researchers must develop a tolerance of failure. And keep on going until their work finally becomes part of that world-changing 2%. Giving up is not an option: we keep researching.
Tackling breast cancer
General cancer mortality rates in Switzerland are falling continuouslythanks to medical progress and the achievements of the pharmaceutical industry in research. In most cases today, breast cancer can be overcome. But of course there are the times when this doesn’t happen.
Some one million people worldwide develop breast cancer every year. In Western Europe, it is even the most common form of cancer, and 6,200 women and 500 men are affected annually in Switzerland, most of them aged over 50. Younger people should also take care, however, as 25% of those diagnosed are below 50 years of age.
In breast cancer treatment, surgery, chemotherapy, hormone therapy and radiotherapy have significantly improved the chances of recovery in recent years. Around 81% of the women and men with the disease are still alive five years after diagnosis, thanks to improved early detection and new therapy concepts. Despite this, however, 13% of patients are forced to live with metastatic disease.
Improving the lives of all patients is a major motivation for researchers in all fields – even if they don’t experience direct contact with the individuals themselves while working in the lab. But as long as the researchers don’t have a 100% perfect solution and haven’t helped all of those affected, they remain dissatisfied. You could also compare their approach to that of a chef wishing to create the perfect recipe for each individual guest. And in order to do so, they prepare the same dish countless times with minimal changes each time. Sometimes they might use less salt, sometimes more water, while sometimes they’ll turn the temperature up, and sometimes down. Until the recipe is adjusted precisely to the individual’s needs.
There’s still no recipe that can cure all breast cancer patients. By the researchers carry on. They keep researching.
On the offensive against viruses and bacteria
Research, prevention and control of bacterial and viral infections: this is what the study of infectious diseases is all about. It’s an area that is booming right now – and not just because of the pandemic. The fact that the field of infectious diseases has developed so rapidly has a lot to do with research into HIV.
Let’s not forget: an HIV infection is still not completely curable. But drug therapy against HIV is currently so successful that it allows for an almost normal life expectancy, and a largely stable life. Research over the past 40 years has made it possible for HIV patients today to take just one tablet a day instead of many.
Significant progress has also been made in the detection of viruses since the 1980s, when identification of HIV was achieved with cell culture. The hepatitis C virus was already identified primarily by molecular means, and the methods are now so far advanced that it was possible to identify the 2019 SARS-CoV-2 pathogen in less than a month. This is mainly thanks to the discovery of polymerase chain reaction (PCR). This technique, which became known to the general public particularly through COVID-19 and was awarded the Nobel Prize, ultimately also made it possible to characterise the human genome within a few years. Despite all this progress, however, alongside all the technical developments in infectious diseases, viruses themselves will probably also develop.
This is due to the fact that, compared to bacterial pathogens, viral pathogens infect the human organism even more frequently: viruses have no metabolism of their own, and are dependent on other cells to live and multiply. Once a virus enters the body, the infected cells themselves are used for reproduction, and the host cell subsequently produces thousands of new viruses. Protected by the cells, antibodies struggle to put up a defence against the intruders.
Viruses are constantly changing, making them difficult to detect. Some lie dormant in the body and are only reactivated in old age, for example, or suddenly produce severe diseases in certain individuals. So in infectious diseases too, then, we keep researching.
The power of small steps
Developing a new drug is an endurance test for researchers, for whom long evenings in the lab and painstaking work are a part of everyday life. The process involved in developing a new drug is slow, and major breakthroughs are rare. Small, repetitive steps over many years are par for the course, and pharmaceutical research is full of hard graft.
Testing and optimising a substance is a process that takes many years, and it is never actually certain that this substance will ever be used to produce an approved drug that can help patients live healthier, better lives.
The hurdle of drug development is followed by many further steps – like finding the right packaging, for example. This is where Vifor Pharma Production Engineer Maëlys Rovetta comes in. “We get involved at an early stage in the development phase to make sure the packaging matches the form of the drug – pill, syrup or gel.”
Her expertise is especially in demand when it comes to the last third of the development process. This is when Maëlys Rovetta works with the team to develop the specific size, shape and material of the packaging for the product in question. “You wouldn’t think packaging could be so complex, but this makes it all the more technically interesting for us engineers.”
In addition to the technical challenge, Maëlys Rovetta and her fellow researchers are always aware of why they do what they do. “It takes all of us – from the chemist, through to me – to make sure patients can collect the products they need from the pharmacy.”
Because after all, the ultimate goal of all research is to improve human health. So whatever it takes, we keep researching.
The long road of drug development
Endurance, enthusiasm and a tolerance of frustration: a researcher has to have all of these. However much expertise is involved, things don’t always go according to plan.
“Setbacks are much more common than success. You take a few steps back, one to the side – and now and again a few steps forward.” Researcher Michael Burgert is very familiar with this route. Having worked in chemical research at Vifor Pharma for over twelve years, he knows that very often you need to keep going over the same rough ground to discover the details that allow you to make progress. “Often it feels like wading through a swamp that keeps on getting deeper. Until you suddenly find the optimal conditions, and finally make it out the other end with an effective product.”
One project comes to an end, another one begins. “We never stand still,” says the researcher. For Michael Burgert, the process starts with a patient need. And then the search for a compound gets going. “We’re currently conducting intensive research into treatment options for people with rare kidney diseases. And as we do so, we keep asking ourselves what we can do to improve their quality of life.”
Both the field of pharmaceutical research in general and Michael Burgert in particular will need a great deal of staying power until the time comes when those patients with kidney disease will reap the benefits of this work. “It’s an amazing feeling to see how a drug can help the people affected. The key milestones in the process give us the satisfaction we need to live each day based on our commitment to keep researching.”