The US National Institutes of Health has kicked off the year by launching several programs that promise to support research into genotyping, biomarker analysis, association studies, and related fields that are likely to drive development of personalized medicine through the end of the decade.
NIH is contributing at least $123 million towards the new programs, with additional funding from a range of partners in other governmental agencies and private industry.
These initiatives should result in a foundation of data that researchers in both the private and academic sectors will be able to make use of in personalized medicine. Industry players in pharmaceuticals and diagnostics are already taking part in some of these initiatives, but there are several opportunities for others to sign on.
These initiatives include:
- a $20 million request for applications from the US National Heart, Lung, and Blood Institute related to genetic variants associated with heart, lung, and blood disorders and risk factors;
- the Oncology Biomarker Qualification Initiative, whose budget is not currently known, of the US Food and Drug Administration, National Cancer Institute, and the Centers for Medicare and Medicaid;
- the Genetic Association Information Network, public-private partnership managed by the Foundation for the NIH that will spend approximately $21 million in private funding genotyping seven diseases, with $60 million more in private funding expected to support future genetic studies;
- the $14 million Cancer Genetic Markers of Susceptibility project, an NCI-funded research project to identify genetic susceptibilities to prostate and breast cancer, for which Illumina will perform genotyping.
- Genome-wide SNP association study services performed on Illumina's platform are now available at the Center for Inherited Disease Research at Johns Hopkins Medical Institute;
- the Genes and Environment Initiative focused on the causes of common diseases and supported by $68 million from the US National Institutes of Health;
The NHLBI RFA
This $20 million RFA, released on Feb. 16, solicits applications for genome-wide association studies focused on heart, lung, and blood disorders and related risk factors. The RFA requires that applicants base their projects on existing population, family, or clinical studies, and applications proposing the collection of samples or phenotypic data will not be considered. The initiative's results are expected to illuminate biochemical pathways leading to disease, as well as the interaction of genetic and environmental factors.
Funding will last for three years for four to six awards.
Data coming out of these NHLBI-supported projects will likely prove useful to investigators in pharmacogenomics and molecular diagnostics — the RFA anticipates that results from the project will lead to predictors of treatment response and predictors of disease, as well as new treatments and prevention strategies. NHLBI will make genomic data from the project available to the scientific community one year after receipt of a curated data set, the RFA said.
Letters of intent are due March 21, applications are due April 20, and the RFA expires on April 21. Peer review will take place in July, council review will take place in August, and the project is expected to start on Sept. 30.
The Oncology Biomarker Qualification Initiative
The OBQI, a joint project of the FDA, the NCI and CMS, appears to focus almost entirely on the use of imaging technologies to detect and monitor biomarkers related to cancer treatment, but genomic and proteomic technologies will play a role as well.
The project aims to establish biomarkers that show a tumor's response to treatment, the chance of cancer recurrence, the likelihood of a response to a particular drug, or the usefulness of a drug under development.
Specific areas of scientific activities include the application of platform technologies for assessing genomic and proteomic alterations, multiplexed molecular assays, and advanced imaging modalities, according to this memorandum of understanding establishing the OBQI.
Monthly working groups will set the OBQI's agenda, and "the government will seek to engage the private sector" in the implementation of some top-priority research projects, according to the MOU. Research for the OBQI will be conducted through several different mechanisms: government agencies may carry out projects directly or through funding agreements; the private sector may perform projects directly or may fund the research; or consortia of interested parties may split projects among their members.
These initiatives should result in a foundation of data that researchers in both the private and academic sectors will be able to make use of in personalized medicine.
As for the goals of the three partners forming the initiative, As part of the alliance, NCI "seeks to develop technologies to improve the detection, diagnosis, treatment, and prevention of cancer;" FDA "is interested in exploring biomarker technologies as assessment tools for use in FDA guidance to facilitate cancer drug development;" and CMS "is interested in the development of evidence to inform reimbursement decisions making about existing or new treatment regimens."
The project is an open-ended effort that will continue "as long as there are biomarkers to look at, and I expect that will be for a long time," NCI spokesperson Dan Sullivan told Pharmacogenomics Reporter sister publication GenomeWeb News in an email exchange.
Funding for the project is similarly open ended, said Sullivan, since specific slate of projects has not been defined. However, NCI's initial contribution is "in the range of a few hundred thousand dollars," he said. In addition, the FDA requested $10 million for the fiscal year 2007 budget, of which "a large part" will go to the Critical Path initiative, he added. The size of the OBQI budget will be depend on the final amount budgeted for Critical Path.
"The NCI investment will vary from year to year, depending on the relative priority of the various projects compared with other NCI priorities, and relative to how much money was contributed by other partners," NCI spokesperson Ann Benner said in a follow-up email exchange.
Parties interested in getting involved with the OBQI should contact the NCI Press Office at 301-496-6641 or at [email protected], Bennner said.
The Genetic Association Information Network
The GAIN partnership, announced Feb. 8, will employ Perlegen Sciences' whole-genome genotyping and existing case-control studies to help uncover the genetic contributions to five common diseases, with studies of two more diseases slated for genotyping investigation by Affymetrix, followed by further efforts.
The three-year GAIN project has issued a request for applications for samples to be genotyped, and it plans to make all of its quality-control tested genotyping data available through the Single Nucleotide Polymorphism Database. All of the GAIN data, including associated phenotypic data, will be made available through the GAIN database to qualifying investigators.
Investigators may submit applications to have genotyping performed on DNA samples from patients with specific diseases and control individuals in case-control studies, but GAIN will not support the collection of samples or phenotypic data. The National Center for Biotechnology Information at NIH will develop databases to manage the genetic, medical and environmental information resulting from these initiatives.
Pfizer has donated $5 million to set up the network, and it has promised an additional $15 million to support laboratory studies of the first five diseases. Affy will likely contribute about $6 million more for further laboratory work toward characterizing two more diseases, although the company did not disclose its financial contribution to the project. The GAIN partnership proposes to raise $60 million in private funding for additional genetic studies of common diseases and is actively seeking additional partners. The Foundation for the NIH will manage GAIN, which counts as its members the NIH, industry, foundations, individuals, and advocacy groups.
Participatants include the US National Human Genome Research Institute, NCBI, as well as other NIH institutes and centers. The partnership also counts Abbott Laboratories as a contributor.
"We believe that this is a critical time to support these public-private initiatives that look at creative ways of funding these studies," since the technology for projects like this have only recently become available, said Affymetrix spokesperson Andy Noble during an interview this week."We believe we can also contribute to the project discussion and project direction by being invoved with the steering committee and by being one of the principal partners," he added.
Cancer Genetic Markers of Susceptibility
Originally announced last November, CGEMS officially launched two weeks ago, and like many other disease-association genotyping studies, its main contribution to pharma, pharmacogenomics, and molecular diagnostics will be the fresh data it will produce and make public. With the goal of spotting even low-penetrance SNPs associated with breast and prostate cancer, much of the information will be novel fodder for drug and diagnostic targets.
The three-year, $14 million project to identify susceptibility alleles for breast and prostate cancer — including low-penetrance alleles — involves the NCI Division of Cancer Epidemiology and Genetics, the NCI Core Genotyping Facility, and the NCI Office of Cancer Genomics.
And CGEMS promises to produce a lot of SNP data. The project aims to first conduct whole-genome scans on approximately 1,200 prostate cancer patients and 1,200 controls, followed by equal numbers of breast cancer cases and controls. Each scan of a case or control will involve the interrogation of more than 300,000 SNPs. The project calls for sequential replication studies to validate 15,000 to 20,000 SNPs in follow-up case-control studies.
Illumina said last week that it would perform rapid genotyping for the project under a subcontract with SAIC-Frederick, beginning with 2,500 male samples for the prostate cancer portion of the research. The company will use its HumanHap300 BeadChip and Infinium assay for the project.
Researchers at the NCI and throughout the extramural community will have access to the validated data via the cancer Biomedical Informatics Grid "as rapidly as possible," according to a DCEG statement.
Genome-wide SNP Association Study Services at CIDR
The Center for Inherited Disease Research at the Johns Hopkins Medical Institute has agreed to offer a genome-wide association service based on Illumina's Sentrix HumanHap300 BeadChip and Infinium assay, the firm said last week. The company has been working with CIDR in a type-2 diabetes gene-association study, and on the basis of the strength of those data, the center has adopted its platform, Illumina added.
The new service will be integrated into CIDR's existing Illumina BeadLab system, which the company said features production-scale sample processing and will use its existing lab information management system, according to Illumina. CIDR is already using Illumina's Array Matrix and GoldenGate assay for SNP linkage and custom genotyping, Illumina said.
The first application deadline for the service is March 1, and customers must specify whether they prefer the company's Infinium I or II assay, as well as their choice of one of three Illumina marker sets, the center said.
Services are free to extramural investigators whose projects are supported by one of the thirteen NIH institutes that support CIDR, since the center is funded through a chargeback mechanism from those institutes. Additional pricing information can be found here. Applications are evaluated through peer review by the CIDR Access Committee.
The Genes and Environment Initiative
If the President's fiscal year 2007 budget is approved by Congress, the GEI will receive $68 million for research into the relationship of common diseases to interaction of genes with environment. The GEI's first-year budget will allow it to spend $26 million on genetic analysis related to common diseases and $14 million on developing new tools to measure environmental factors.
The funding level should allow the pursuit of "several dozen" disease studies, but none has yet been chosen, the NIH said in a statement.
— Chris Womack ([email protected])