New Initiatives to Improve Diagnostic Data Access

A welcome side-effect of the recent pharma trend towards streamlining, outsourcing, and establishing collaborative network strategies is the increasing availability of data and resources that others can draw upon more easily. The phenomenon is encouraging the formation of precompetitive alliances, often diagnostics focused, especially in oncology, where the vast majority of biomarker work has occurred.

A welcome side effect of the recent pharma trend toward streamlining, outsourcing, and establishing collaborative network strategies is the increasing availability of data and resources that others can draw upon more easily. A small but growing community of researchers and entrepreneurs is seeking to tap into available resources, or to find more expeditious ways to catalog and share ever-expanding amounts of information. The phenomenon is encouraging the formation of precompetitive alliances, often diagnostics focused, especially in oncology, where the vast majority of biomarker work has occurred.

The most notable recent example of this trend came late February, when Merck & Co. Inc. donated a sizable chunk of resources to Stephen Friend, MD, PhD, its former SVP, cancer research, to be one of the building blocks of his new not-for-profit initiative, called Sage, which will develop biological networks across tissues and organs that model disease. Sage will provide an open access platform for researchers to run experiments that gauge the effects of perturbing these complex networks. (See "A Friend-ly New Resource for Biomarker Validation?," START-UP, March 2009 (Also see "A Friend-ly New Resource for Biomarker Validation?" - Scrip, 1 Mar, 2009.).)

As part of a streamlining of R&D operations, last fall Merck decided to shut down its Rosetta Inpharmatics LLC research site in Seattle. Friend had co-founded Rosetta, which Merck bought in 2001 for $576 million to bring in-house a state-of-the-art capability for analyzing transcript profiles for target selection. [See Deal] He left Merck in February, to launch Sage. Merck is giving the vast majority of Rosetta’s high-performance computing operation to Sage. It is also offering up some of the genomic data Rosetta has amassed, excluding, of course, any related to ongoing proprietary programs.

"We realized that part of what Rosetta was doing was putting a lot of data into public databases anyway," notes Tony Ford-Hutchinson, PhD, EVP and head of basic research at Merck. "We really could not afford to continue doing that." Merck is keeping significant internal capabilities to be able to interrogate these public databases in the same way it interrogates genomic databases, which should enable it to maintain a competitive advantage even if the data are available to others. "You need to have good groups internally that can exploit [the data] rapidly for drug development," Ford-Hutchinson says. "I think it’s no different than the way we currently operate."

Friend has approached many Big Pharma companies seeking their support for Sage, including Eli Lilly & Co., whose VP of discovery research and clinical investigation, William Chin, MD, is an advocate for precompetitive consortia among industry players. (Like Merck, Lilly has championed the need to share resources, giving up the notion of becoming a fully integrated pharmaceutical company—a FIPCO—in favor of a network strategy—a FIPNet. See "Lilly and Merck Lead the Way with Asian FIPNet Strategies," IN VIVO, May 2008. (Also see "Lilly and Merck Lead the Way With Asian FIPNet Strategies" - In Vivo, 1 May, 2008.)) "I think there are levels of interaction that could occur [with Sage]," Chin says.

While he doesn’t foresee companies willing to share compound data now, Chin thinks even that is possible in the future given a marked change in pharma culture, which he sees as inevitable. "We’ve always been super-competitive, but what we’re seeing is we have to be more particular in terms of what we compete on. I’m a believer that a lot of this begins with trust, that people need to learn how to work with each other a little more, then perhaps companies would be more at ease in sharing more information."

Although Sage has not finalized any deals with pharma companies (including the initial transfer of materials from Merck), Friend has raised $5 million from private sources to get it off the ground, and estimates the venture will need $20 million per year during a three to five year incubator phase, for which he is turning to private foundations, governments, pharma partners, IT partners, and tools and applications builders, including diagnostics companies. Initially, Sage will reside within labs at the Fred Hutchinson Cancer Research Center and Yale University, with more sites to come. Friend expects the number of linked-in labs to proliferate in the same way that Facebook spread from Harvard to other universities, then into the mainstream, as the underlying tools and techniques are refined.

Sage will principally focus on helping researchers gain a better understanding of fundamental disease processes and the biochemical pathways that are important in different pathological states, with an eye toward gaining a much better understanding of targets and how they can be modulated with drugs. But the data fed into the Sage system should also help better identify patients with particular risks for disease.

This kind of patient segmentation is critical in cancer therapy, especially given reimbursement pressures. That’s because the increasing number of expensive biologics benefit only a small percentage of patients, even if they do so in a spectacular way. Large population studies of such drugs, historically the sine qua non in drug development, tend to show an increase in survival of a month or two, leading payors to question the benefit. (In the UK, for example, the National Institute for Clinical Excellence, which is charged with giving guidance on best practices, advises against paying for them for that reason.) "If you can personalize your medicine to get really good outcomes in a smaller population, then the benefit to the payor is more persuasive," Ford-Hutchinson explains. The task is even more difficult given that cancer therapies are almost always used in combinations.

Of course, the smallest denominator for such an approach is a single patient. Jay M. ("Marty") Tenenbaum, PhD, chairman and chief scientist at CollabRx Inc., believes it’s possible "to drive clinical R&D in real time" by looking at patients one at a time, instead of looking at cohorts of patients. CollabRx is beta-testing a program—CollabRx ONE—offering individualized consultations to oncologists, backed by the company’s bioinformatics capabilities. (Tenenbaum is a former Internet entrepreneur; the team at CollabRx includes computational biologists and clinicians.)

"We start with one patient," Tenenbaum says, and ask what information and measurements can be put together around this one patient to understand the disease driving that individual’s tumor. Contrast that with a typical study, where lots of patients are aggregated with a goal of identifying the common elements among them. In cancer, in effect that means lumping many diseases together, each of which is subtly different—a different mutation, or a different combination of pathways that are involved. By looking at one patient at a time, CollabRx hopes to get deeper data than is traditionally available in a diagnostics context. "You absolutely can get back to the point where you are doing validated studies with multiple patients," says Tenenbaum, "but you do that driving it off the hypotheses formed from individual patients. It’s a much cleaner hypothesis." CollabRx has consulted with five patients in this way, and based on that initial cohort, is looking for an academic institution to partner in a pilot study comparing a standard treatment process with the CollabRx ONE process.

An important part of Tenenbaum’s vision is to augment CollabRx’s resources through a not-for-profit network of users and service providers--including virtual biotechs, labs, and, potentially, diagnostics companies--called the Health Commons, an offshoot of Science Commons, a project aimed at making the transfer of research information easier and more transparent.

There’s a lack of good information about the physiological consequences of many drugs. "So many things are out there now and even off patent that may have broad new applications in medicine that haven’t been discovered or figured out," says Lee Hartwell, PhD, president and director of the Fred Hutchinson Cancer Research Center (and co-founder of Rosetta). This is especially true with respect to combination therapies in cancer.

To help bridge that gulf, Hartwell has spearheaded the formation of the Partnership for Personalized Medicine (PPM). Although technologies are becoming available that will lead to valuable new diagnostic tests, "there’s no sound economic pathway to bring them to patient care, because the ROI is not big enough and you still need clinical trials," he says. (That’s changing for a handful of high-value diagnostic products, however. See "How to Earn the Economic Payback Diagnostics Companies Deserve," IN VIVO, March 2009 (Also see "How to Earn the Economic Payback Diagnostics Companies Deserve" - In Vivo, 1 Mar, 2009.).) Hartwell’s group is trying to engage payors and providers to invest in the research that will help to validate more new diagnostic tests. With the support of two Arizona-based philanthropies, PPM has set up a validation center for molecular diagnostics at the Translational Genomics Research Institute (TGEN), a genomics center in Phoenix. The model, bridging the space between the commercial and not-for-profit sectors, is similar to that of the C-Path Institute, which is more focused on biomarkers for drug development rather than clinical diagnostics. (See "C-Path Proposes NSCLC Initiative for EGFr Drugs and Diagnostics," IN VIVO, July 2006 (Also see "C-Path Proposes NSCLC Initiative for EGFr Drugs and Diagnostics" - In Vivo, 1 Jul, 2006.) and "A Critical Test for FDA's Critical Path Initiative," The RPM Report, February 2006. (Also see "A Critical Test for FDA's Critical Path Initiative" - Pink Sheet, 1 Feb, 2006.))

Hartwell’s idea is to set up a commercial-style high-throughput high-quality-control center in an academic and non-profit environment and then to go out and form partnerships with payors and providers. Much of the initial outreach has been international, given that with the exception of the US, almost all of the countries in the world are single payor systems—"where it’s easier to tell the story," he says. PPM’s first project, on lung cancer, is being supported by Luxembourg.

--Mark L. Ratner