An innovative partnership forged by the National Institutes of Health, 10 pharmaceutical companies and several nonprofit organizations is expected to improve the chances that the right targets will be found for development of new drugs to treat rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Called the Accelerating Medicines Partnership (AMP), the alliance is using a model different from traditional drug development by funding collaborative efforts to find targets for effective therapeutics more quickly.
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Explore This IssueOctober 2014
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The “science is ripe,” NIH Director Francis S. Collins, MD, PhD, said at a recent press conference. “We’ve come a long way in recent years in our understanding of disease. As a result of technological advances and genomics, proteomics, imaging and more, researchers have increasingly been able to identify fundamental changes in genes, proteins and other molecules that predispose to diseases whose causes have vexed us for all of history.”
The AMP will focus on RA and SLE, as well as Alzheimer’s disease and type 2 diabetes, with the partners investing more than $230 million in the total project over the first three to five years. The budget for the RA/SLE portion is $41.6 million, with that amount split roughly 50/50 between the NIH and its partners in the pharmaceutical industry.
Chemical Pathways in RA & SLE
RA and SLE research will focus on genes, proteins, chemical pathways and networks involved at a single-cell level, according to the NIH. In addition to analyzing single cells and groups of cells involved in autoimmunity, the project will collect tissue samples from people with RA and SLE for molecular analysis, develop computational tools to integrate data types so that molecular pathways can be understood and make the data available to the broad research community for further analysis.
Jennifer Bell, PhD, research director of the Lupus Research Institute (LRI), says she is hopeful that AMP will generate “big data” on human lupus that can speed up the validation of pathways and new targets for diagnostics and drug development. Dr. Bell says the LRI and the Alliance for Lupus Research (ALR) are represented on the steering committee of AMP’s lupus/RA program and will have input about the governance, management and direction of research.
The ALR and LRI bring the unique perspective of nonprofit organizations that have been “an engine for discovery in lupus and, most importantly, the voice of lupus patients,” she says.
Lupus research, up until this point, has not been part of such a large-scale and close collaboration among the government, industry, nonprofit research organizations, academics and patients, Dr. Bell says. The AMP’s emphasis on collaboration among those parties should help propel research to the “next level by generating huge datasets on signaling pathways in human lupus.”
“In our work we have learned that breakthroughs often come where least expected from informed inferences. Importantly, the AMP datasets will be available not just to the NIH and large pharma companies but to all who are interested to analyze it, including innovative biotech companies, researchers from diverse academic disciplines, and patients,” she says.
The Arthritis Foundation, the Lupus Foundation of America and the Rheumatology Research Foundation are also partners in the project. David Karp, MD, PhD, president of the Rheumatology Research Foundation, says this collaboration could yield major breakthroughs. “If the program is successful, it may also open the door for many similar discoveries in other autoimmune diseases that would mean better treatments for even more patients, which is an important goal for the Foundation.”
The entire biomedical research community, along with the entire patient advocacy community, has a shared interest in compressing the timeline, reducing the cost & increasing the success rate of new targeted therapies.
AMP’s focus on RA and SLE is divided into three research phases, with Phase 0 testing the different ways to obtain and prep tissue. Initial analytic runs will be conducted with the aim of developing standardized methods in small numbers of homogenous samples in at least two diseases. Phase 1 will analyze the standardized analytics developed in Phase 0 in blood and tissue cells and will conduct trial runs of additional selected analytics. The number of samples will be sufficient to inform power calculations and establish feasibility studies of the tissue analytic and sample type, source, and acquisition approach.
At least one Phase 1 study in RA and one in SLE should be completed by the end of the second year of the project, according to the NIH. This phase will include analysis of samples from people without RA or SLE to identify pathways that distinguish disease and nondisease tissue.
In Phase 2, studies will be conducted on the recommendation of the AMP RA/SLE Steering Committee and approval by the NIH Program Official. Testing will be conducted in larger patient populations, with patient stratification expected for comparisons within a disease, such as treatment responders vs. nonresponders in RA, and before-treatment vs. after-treatment results for SLE. The final 12 months of the project, projected for 2019, will include preliminary target validation.
A central aim of AMP is to “harness the rich, new resources of biological knowledge and find better ways to develop greater numbers of effective therapeutics at a faster pace,” Dr. Collins says. All data and analyses generated by the project will be considered “precompetitive” and will be made freely available to the entire biomedical research community. After the initial discovery stage in which the AMP team collectively identifies the most compelling target, the “full competitive power of the pharmaceutical industry will kick in to develop the actual therapeutic molecules,” he added.
AMP partners have developed detailed and milestone-driven research plans in close collaboration through a shared, integrated, governance structure, Dr. Collins says. “We have rolled up our sleeves, left our affiliations at the door and put real skin in the game.” Discoveries about these diseases will not just benefit the pharmaceutical industry, he added. “The entire biomedical research community, along with the entire patient advocacy community, has a shared interest in compressing the timeline, reducing the cost and increasing the success rate of new targeted therapies.
“We believe the stars are aligned and the opportunities ripe for all sectors of the research enterprise to join forces to resolve the critical issue of finding better targets so that we can develop better drugs at a more rapid pace,” he says.
Kathy L. Holliman, MEd, is a medical writer based in Beverly, Mass.