Using human genetics to improve drug discovery and development, and minimize costs, risk and time to market are the two main themes of a paper by Vincent Mooser, MD, Professor in the Department of Human Genetics at McGill’s Faculty of Medicine and Health Sciences, and his team, published in the August 23rd, 2023 edition of Nature 

In the paper titled, “From target discovery to clinical drug development with human genetics,” Dr. Mooser and his team suggest that academia and industry are at a pivotal point in the use of genetics for drug advancement. “The entire community was hoping that discovering the genetic basis of diseases would reveal new targets, better targets, faster targets. The question we asked is: with governments, public agencies, academics and the industry, having invested billions of dollars in human genetics, what has really been delivered in terms of new drugs?”  

The study notes that research and development by the top 15 pharmaceutical companies amounts to more than $60 billion yearly. “Discovering and developing new drugs is a very risky business. It’s also very expensive and it takes a significant amount of time. And the output is relatively minimal. We’re talking about approximately 15 new drugs approved yearly by regulatory agencies. If you calculate the ratio you come up with close to one to five billion dollars to launch a new drug,” says Dr. Mooser. 

Because the first human genomes were sequenced and published in 2002, and it takes a minimum of 15 years to develop new drugs, Dr. Mooser says now is a good time to answer questions that will provide direction regarding future investments in human genetics. “Any information relevant to human biology which can be gleaned and collected to accelerate the pace, reduce risk and diminish cost would be advantageous. That has been one of the major reasons why people have invested so much in human genetics since the turn of the century.”  

The list of questions begins with determining returns on investment. That, in itself, turned out to be complicated says Dr. Mooser. “Firstly, because there’s a lot of information we don’t have access to, for example private information from pharmaceutical companies. Secondly, can we confirm that the discovery of these drugs was driven by human genetics? To discover and develop new drugs incorporates knowledge from a variety of different sciences, genetics being one. But you also need to have biochemistry, biology, pharmacology and all this type of information, which in the end leads to a new drug. We acknowledge this limitation very clearly in our article, and that we are only seeing a fraction of what genetics has been delivering. And we intentionally use as the definition of success, only drugs which have been approved by the FDA or its equivalent.” 

In their analysis, Dr. Mooser and his team demonstrate that human genetics has been instrumental in the discovery and development of 60 first-in-class marketed drugs and that many new medicines driven by human genetics are in the investigational phase. “In the development phase, you have a new molecule or a new suspected medicine. You give that to humans, and you want to show that it works, essentially. For example, to prevent heart attacks statins were developed back in the ‘80s as a way to lower the bad cholesterol level in your blood, or LDL cholesterol. Testing on humans showed that statins not only lower cholesterol but also prevent heart attacks. Such trials cost $500 million. We claim that if we use genetics we can make these trials shorter, better and less expensive,” notes Dr. Mooser. 

To meet these objectives, Dr. Mooser says large cohorts are required to draw patients from. “Population-based cohorts like the U.K. Biobank represent phenomenal resources. However, we also need to build disease-based cohorts of people who consent to the use of their data and sample for research, and consent to being recontacted in the future to take part in clinical trials.” 

To conduct drug trials industry typically enlists academic institutions that have the infrastructure to carry them out quickly and economically. Dr. Mooser points out that McGill meets both of these requirements. “We are blessed here at McGill, and in the province, because we have some very good research, a unique population base, and strong investment in genetics. We also have the capacity to recruit patients very rapidly for trials,” notes Dr. Mooser. 

For instance, should a pharmaceutical company want to conduct a trial on a drug for correcting or preventing kidney problems in diabetic patients, McGill is able to construct large databases of patients. “We would need to have information on their kidney function in the medical records and we need to be able to contact an individual to see if they would be interested in being part of a trial. And we need to do this rapidly because speed is of the essence in the pharmaceutical industry. If you have a drug which has the potential to make $1 billion of revenues annually, every day is costing companies $3 million. Industry goes where the patients and investigators are,” Dr. Mooser says. 

McGill is in the process of building a cohort at the Jewish General Hospital (JGH) called BioPortal, whose goal is to recruit thousands of documented and consented patients. BioPortal is led by Brent Richards, MD, at the Lady Davis Institute of the JGH. Recruitment for BioPortal has already begun, with an initial focus on diabetes.  Among others, the initiative will benefit McGill’s “DNA to RNA (D2R)” program recently funded by a Canada First Research Excellence Fund grant of $165 million from the Government of Canada. 

Since August 2019, Dr. Mooser holds the Canada Excellence Research Chair in Genomic Medicine at McGill. His Chair is titled, “From Genes to Next Generation Therapies.”