The Montreal Heart Institute and Génome Québec announced last week that they had formed a Center of Excellence in Personalized Medicine that they hope will “position Québec and Canada as world leaders in the optimization of personalized treatment.”
The project, which is the result of CA $22 million ($21.6 million) of investment over five years from the Canadian government, as well as private and other public investments, aims to “develop approaches and methods that will optimize treatment and ensure their rapid and productive transition from the research stage to use in clinical practice.”
The Government of Canada’s Centers of Excellence for Commercialization and Research has so far invested CA $13.8 million, and the remaining funds will come from private and public investments, including the Ministère du Développement économique, de l’Innovation et de l’Exportation of Québec.
The Center, which was developed in collaboration with industry partners such as Pfizer, AstraZeneca, and Roche, intends to use PGx tools and strategies to optimize drug treatments and introduce new drug/diagnostic combination products.
Jean-Claude Tardif, director of the MHI Research Center and professor of medicine at the Université de Montréal, spoke to Pharmacogenomics Reporter this week about the center and how this project stands to be one of the major international efforts to try to bring pharmacogenomics from the bench to the bedside.
How was the decision made to start the center, and what are its aims?
We are globally moving away from a paradigm of one drug, one dose, or the blockbuster strategy. And rather, for safety and efficacy reasons, trying to go toward a more personalized approach to medicine. This means that we should take into account the genetic background of patients and other factors for the prescription of medication or other therapies.
So, over the past four years, we’ve invested a lot on infrastructure and focused projects on personalized medicine. We received a CA $22 million grant from Genome Canada for cardiovascular pharmacogenomics, focusing on novel anti-atherosclerotic agents and also cardiovascular drugs that are being used right now to try to improve their safety and efficacy. We’ve built a state-of-the-art, GLP-grade pharmacogenomic center.
There was also a CA $15 million grant to build infrastructures, and get genotyping and sequencing machines that we received from the Canadian Foundation for Innovations. Basically, there have been a number of initiatives around personalized medicine, and we have about CA $80 million for building infrastructure and projects pertaining to pharmacogenomics. The last grant we received funded the building of this Center for Excellence in Personalized Medicine.
One of your aims is to accelerate targeted drugs and diagnostics from the research stage to commercialization. How do you plan to achieve this?
There are a number of strategies and objectives. One of them is certainly to go beyond the scientific finding of identifying a genetic determinant of a given drug or a sponsor drug. But we also want to go to the next step, which is translating this finding into something clinically useful for physicians and patients. So, that’s certainly one approach.
The second aim is also to develop tests that can guide the better use of drugs, but we also, in certain circumstances, would like to develop in parallel the diagnostic tests with the development of the drug. So the co-development of drug and test is also part of our objective in this center.
How do you plan to bring the drug and diagnostic companies together?
To submit this proposal for the Center of Excellence, we did have to show written support from industry. In fact, in this center, we have 14 companies from pharma, biotech, and genomic sectors that have all supported us in writing, and most of them with cash contributions. So, most of the large pharmaceutical companies are already part of the center, as well as a lot of the genomic companies. They will be a part of this development, and it’s in their best interest to be a part of this effort as it is happening.
Can you disclose which companies have signed on?
Yes, I can mention a couple of our pharmaceutical companies. But for obvious reasons, there will probably be a couple of other announcements, jointly from us and the genomic technologies companies, in the weeks to come. But in terms of the pharmaceutical companies, we have the support of Pfizer, Roche, AstraZeneca, among others. We have six major pharmaceutical companies that are partners with us on the center.
Where do these companies feel they can best use pharmacogenomics in their drug development programs?
At several levels. First, they use pharmacogenomics to stratify or to select patients for late, Phase III/IV trials, based on the early findings from the early phases of drug development. Second, once they have the results of a Phase III trial, they want to try to understand what are the genomic determinants of better safety or better efficacy, so this information about better clinical use of these drugs.
There was a White Paper a couple of years back from the US Food and Drug Administration strongly recommending all pharmaceutical companies to incorporate a pharmacogenomic assessment part to their drug development. In some circumstances, the use of the drug may very well be determined based on the pharmacogenomic marker. But obviously, we are going beyond pharmacogenetics. We are also integrating proteomic approaches; we’re not only looking at SNPs or single genes, but rather are looking at genome-wide association studies; and we’re integrating haplotypes into this. It’s really a comprehensive approach.
Would products resulting from these Rx/Dx collaborations be only for the Canadian market?
We are not investing CA $80 million in pharmacogenomics here in Montreal, so this remains a local resource. Or that the impact of this is local or national. At this center, this group of scientists that we have recruited is really to have an international impact, both in the scientific world, and in the translation in to clinical aspects, and in the business models.
With the increased introduction of PGx strategies and diagnostic tests, how will this impact the regulatory system in Canada? How will this system need to change?
We’ve been having ongoing discussions with the Canadian health protection branch about that very subject. The FDA White Paper came before anything Health Canada did on the subject. We’ve been having very open discussions with our regulators in Canada and they have issued a document where we gave our opinion and interacted with them. So this was a first major step in Canada that followed a couple of years after the FDA took the lead as far as regulators go.
Are there concerns in Canada regarding the need for additional validation of these tests, since a greater number of genetic tests are being introduced to physicians and patients, and some believe the market may not be ready?
I think it’s not that the “market is not ready.” I think the market will be ready for approaches that improve the safety and toxicity of medications, whether it is cardiovascular medications, or medications for cancer or neurosciences. … With regard to whether these tests are validated enough, I’d be the first one to say that if something has not been validated enough, then it should not be used in the clinic. That’s why we’ve invested massively in this Center of Excellence. We have a pharmacogenomics center that we just built, which is GLP grade. We have CA$80 million with which to do pharmacogenomic research, and we have access to large patient cohorts, we are sitting very close to a coordinating center for clinical trials that is able to handle large databases of several thousands of patients. … These results need to be robust, and validated, and replicated in several cohorts. Now we have the tools, the infrastructure, and the budget, to actually do that.
So, I don’t think it’s a question of the market not being ready. If the data are robust enough, clinicians will be convinced to use it. Then, the last part will be education. We will need to educate clinicians and help them to drive guidance engines and tools so that they know what to do with the results. But all of that has been incorporated in our strategy.
Can you discuss any of your upcoming projects?
The infrastructure is focusing on four disease areas: cardiovascular, cancer, neuroscience, and inflammation. As far as our major projects right now, we’re looking at the pharmacogenomics of novel anti-atherosclerotic agents. We have a large project looking at the pharmacogenomics of statin-induced muscle toxicity. These are the two major projects that we can announce for now. We’ll be able to announce a third large project in the months to come in cancer, and a fourth one in inflammation.
Hopefully, we think this is going to be, for pharmacogenomics, really one of the major international resources to move this science forward, not only at the bench level, but then translating this into something useful for patients.