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PGx to Play Role in C-Path Plan to Build Orphan Disease Database; Goal Is to Spur Drug Research

Pharmaceutical and diagnostics companies, especially those using pharmacogenomic technologies, may get new incentives to pursue orphan diseases in about six months if a new initiative at the Critical Path Institute takes hold.
Ellen Feigal, director for medical devices and imaging at the C-Path Institute, is heading up a collaboration with physicians, patient groups, and researchers to create a Rare/Orphan Disease Registry in order to support new diagnostic and therapeutic clinical trials for disorders that offer little financial incentive for pharmaceutical companies to target on their own.
The registry will consist of databases and contact information, and could eventually become a storehouse of biomarker data and other information useful to companies seeking pharmacogenomic components to orphan diseases.
The databases could be used help to identify patients who are best suited for clinical trials based on genotype/biomarker data, match marketed drugs to new uses in orphan diseases, or to monitor biomarker or target discovery to support new drug development.
The registry is part of the C-Path Institute’s Opportunities List and will eventually include clinical, patient, and scientific information contributed by physicians, patient groups, and researchers.
The registry would also provide a way for these individuals to find each other, such as when researchers are searching for clinical trial subjects. It will probably operate as a web-based resource with different portals, and it will likely not require a subscription fee, said Feigal.
The C-Path Institute hopes that the registry will encourage drug makers to begin looking at orphan diseases, which, because of their small patient populations, typically fail to generate adequate numbers of samples, demographic data, or disease histories to support investigations.
“This information and this access to physicians and to patients would hopefully be quite a magnet for companies to spend their attention in looking at these areas,” Feigal said. “The point is to develop an infrastructure that would be usable across many orphan diseases, and that eventually could be applicable to common diseases as well.”
In collaboration with patient advocacy groups, C-Path plans to launch a pilot program in about six months to support drug and diagnostic development in three orphan diseases, according to Ray Woosley, president and CEO of the institute. These diseases and organizations are: San Joaquin Valley Fever, with the Valley Fever Center for Excellence; adrenocortical carcinoma, with the Advancing Treatments for Adrenocortical Carcinoma Fund; and Niemann-Pick disease, with the Ara Parseghian Medical Research Foundation.
“Right now, we’re focusing on those diseases that are hardest,” Feigal said. ”We’re focusing on an area where there are relatively small numbers of patients where it’s critical to get people together to form that critical mass” necessary to attract drug and diagnostic developers.
As defined by the US Food and Drug Administration, an orphan disease has a prevalence of fewer than 200,000 in the United States. There are roughly 6,000 to 7,000 orphan diseases affecting approximately 25 million people in the United States, according to Woosley.
The PGx Carrot
Companies interested in pharmacogenomic product development could find the registry’s biomarker information useful, according to Woosley, who said pharmacogenomics is “a big part” of the plan.
In theory, Woosley said the databases would contain genotype and biomarker data that would help identify patients who are best suited for clinical trials. The information could also help match marketed drugs to new uses in orphan diseases, and support new drug development through biomarker monitoring or drug-target identification, he said.

“This information and this access to physicians and to patients would hopefully be quite a magnet for companies to spend their attention in looking at these areas.”

Also, the institute plans to use the registry to produce new disease models for more efficient clinical trials, he added.
In some cases, industry should be able to work backwards — from treatments for these very specific orphan diseases into larger indications, said Woosley.
He cited the example of congenital Long-QT syndrome, in which patients have specific genetic deficiencies that cause the disease. In more common, environmentally triggered forms of the disease, such as drug-induced Long-QT syndrome, patients often have minor mutations predisposing them to the disease under certain conditions. Treatments and diagnostics for the congenital disease could possibly be applied to a broader spectrum of Long-QT, he said.
Beyond the pilot program, C-Path plans to greatly expand the project. Ultimately, the institute hopes to build up the registry to support research in every orphan disease.
The C-Path Institute is still seeking funding for the project, and it is providing all of the seed money to get the registry off the ground, said Woosley.
Feigal cited the system supporting the development of Novartis’ Gleevec, which included a similar “critical mass” of researchers and patient groups, as an example of the kind of network C-Path and collaborators want to create. C-Path was not involved in that effort.
“What really helped get [the Gleevec alliance] going is that there was a critical mass of physicians, of patients — things came together well in looking at a drug in a relatively rare disease — in both chronic myelogenous leukemia and gastrointestinal stromal tumors,” she said. Gleevec is approved for those indications.
Just what kind of information will kick-start drug and diagnostic development depends on “just how orphan a disease it is,” said Donald Small, an investigator in acute myeloid leukemia and a professor of pediatric oncology at Johns Hopkins University.
The size of a drug or diagnostic market is affected by how often patients buy products for their disease. “If it’s a medicine they take chronically, the companies have the potential to realize decent profits from it,” Small said.
However, it is probably still going to be hard for companies to profit in orphan disease areas that have only a couple of thousand patients, he added.
For a researcher or company interested in an orphan disease, there may not be enough samples, demographic data, or disease histories to support investigations, said Small.
“A place like [the Rare/Orphan Disease Registry] could pull all of that together,” he said. “That’s the place that I think it really could be a great benefit.”
On the regulatory side, the passage of the Orphan Drug Act of 1983 sweetened incentives for companies to pursue drugs in orphan diseases by granting seven years of marketing exclusivity.
Other incentives for orphan-disease treatments include tax credits from the US Internal Revenue Service for clinical development costs, fee waivers and protocol assistance from the FDA, and FDA grants for clinical studies.
Since the Act’s passage, the number of treatments for these diseases has increased to about 270 from about 10, said Feigal. “That’s been a very nice incentive, but … there’s a long way to go, and we want to accelerate progress as much as possible,” she said.

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