Name: Hakan Sakul
Position: Senior director of molecular profiling at Pfizer Global Research & Development
Background: Statistical genetics leader at Sequana Therapeutics in La Jolla, Calif., 1995 to 1998; director of statistical genetics, human genetics and pharmacogenetics programs with Parke-Davis Pharmaceuticals in Alameda, Calif., 1998 to 2001; vice president of statistical genomics at Ardais in Lexington, Mass., February 2001 to October 2001.
Education: PhD in quantitative genetics at the University of Minnesota, 1990; postdoctoral studies at the University of California, Davis in quantitative genetics, animal genetics, and international agriculture, 1990 to 1994.
During Pfizer’s annual R&D day Nov. 30 in Groton, Conn., the company highlighted its advances in personalized medicine by touting the development of its investigational HIV drug Maraviroc.
Pfizer used Monogram Biosciences’ HIV-tropism assay, Trofile, to determine the CCR5-tropism status of patients enrolled in two Phase III clinical trials. If Maraviroc is approved, the Pfizer/Monogram partnership extends into a symbiotic commercial agreement in which the assay will be used to identify CCR5-tropic patients who will most likely benefit from the drug [see PGx Reporter, 12-06-06].
Pharmacogenomics Reporter caught up with Hakan Sakul, senior director of molecular profiling at Pfizer Global Research & Development, to discuss Pfizer’s current areas of focus and future plans in the arena of pharmacogenomics and personalized medicine.
Other than the HIV space with the investigational drug Maraviroc, what other therapeutic areas is Pfizer looking into to develop personalized medicines?
We have a group that includes pharmacogenomics and includes other ‘omics’ — metabolomics, proteomics — and we recently added some capabilities in the area of RNA profiling. These groups have been put together not long ago under one umbrella called molecular profiling, though they have been around in the company over the last 10 years.
[For] anything we do in diagnostics there has to be some sort of a scientific pipeline bringing the substrate for any sort of diagnostic partnership in the end. We work from idea all the way to loss of expiration on our drugs. We cover that whole spectrum. We have innovative ways of doing this. Our scale and access to clinical trial material allows us to work across all therapeutic areas. Pfizer works in 11 therapeutic areas [including atherosclerosis, oncology, diabetes, obesity, rheumatoid arthritis, HIV, schizophrenia, liver disease, and Alzheimer's, among others.]
We do have a bio bank, a rather recent development, where we bank all our samples to enable that level of work. The answer is, yes, we do work across other disease areas. Maraviroc presents a very nice application of diagnostics for a compound that Pfizer is on target to file in the next months.
What are the barriers to Rx/Dx partnerships?
When you talk about a diagnostic, you’re talking about a real compound, one perhaps in development, unless you’re looking for markers of a disease state.
Say you’re trying to identify Alzheimer’s and you’re trying to identify early markers as opposed to using the process for Maraviroc, where the drug is in the process of getting filed and it’s going to hit the markets, and you need a companion diagnostic. They are two different scenarios, but the common denominator is that there is some sort of diagnostic marker, either phenotypic or genetic.
When you think about the barriers, part of it is that the science isn’t always delivering because science is evolving in many of these areas. We have interest like any other company in making diagnostic assays available for use. Alzheimer’s is one area of interest. But if you look at any diagnostics in that area, what you’ll find is science and technology are both evolving in that area. There isn’t something available. It isn’t so much the business being the barrier, but science is the barrier. That’s true for a lot of it.
The human genome was sequenced five years ago and we’re still trying to learn what’s really in it. We hope that there will be more and more genes found, published, and validated. Companies out there will develop diagnostics using those markers, which then will be substrates for the kind of work we do internally. Although we have seen a lot happening in technology and science, we still need to see a lot more happening.
What are you looking to achieve in the pharmacogenomics arena?
The pharmacogenomics effort has been around for quite some time [at Pfizer]. Our work in the pharmacogenomics of diabetic complications [is] one example of many we have. The purpose was to identify markers from a list of candidate genes in an effort to increase efficiency in clinical trials.
A particular genotype in this marker in diabetic patients made them less likely to progress to renal dysfunction when they had diabetes. These are patients who are less likely to progress to renal dysfunction, not individuals likely to progress. There’s a distinction there that I want to make. We don’t have a marker in this case that would allow us to give patients protection from renal dysfunction. This particular marker, if it exists in a type 2 diabetic patient who would be less likely to progress, you could use this information in clinical trial enrollment. You are looking for individuals and you are concerned they might proceed to renal dysfunction, so you could identify individuals [who are potentially] better to enroll in a clinical trial and take your experimental drug so the side effect in this case would be less likely.
This is one result we hope others will replicate because there is nothing like external replication of our results. This is the reason at the American Society of Human Genetics meeting [in New Orleans in October] I presented major depression genome scan results … to release data to the public domain and contribute to the scientific literature. Another reason was that we were interested in others taking a look at the markers that came out and telling us if they see the same significance or not. It’s very important that we put these kinds of data sets out there.
What is Pfizer’s role in GAIN?
[The Foundation for the National Institutes for Health announced in February the launch of six studies to support large-scale genomic studies under a public-private partnership project called the Genetic Association Information Network, or GAIN. Pfizes was named a GAIN partner.]
Pfizer’s role [in GAIN] was really as an enabler. To come in and provide some funding to get this started. All the data to come out of these genome scans will immediately become public, and in fact Pfizer will see the data no sooner than anybody else.
So here is another effort to put data in the public domain on disease states. The samples used in this effort will not be from clinical trials but from human genetics work. Basically we’re looking for markers underlying diseases, so it’s not really drug response data. It’s really more disease-association data, which would then help with disease states and identification of diseases in earlier stages in people’s lives.