Imaging systems are lumbering into personalized medicine.
In a deal announced this week between Roche and General Electric Healthcare, the companies will combine a novel GE imaging ligand with positron-emission tomography to track patient response to a Roche anti-amyloid Alzheimer's disease drug during trials.
The collaboration, in which PET will monitor a clinical drug trial, is the first of its kind since Woodcock spoke at the Tri-Conference. Both companies hope that the trial will result in data that will allow them to gain US Food and Drug Administration drug approval of their products — an imaging molecule in the case of GE, and an anti-amyloid in the case of Roche. "It really does show a significant forward movement toward personalized medicine that everyone's talked about; there's been great speculation, and now you're beginning to see some very concrete things happening," Dennis Burns, vice president, global head of business development at Roche, told Pharmacogenomics Reporter.
Momentum seems to be building. At the April Molecular Medicine Tri-Conference in San Francisco, Janet Woodcock, acting deputy commissioner for operations at the US Food and Drug Administration, entreated diagnostic and imaging companies to employ molecular imaging technologies during clinical trials, although she spoke mostly about their use in cancer-drug development.
The companies intend to separately analyze patient data in order to independently evaluate each of their own products, and to submit data to the FDA individually. GE will submit all data related to the imaging agent, called Pittsburgh Compound B, or PIB, to the FDA for approval as a drug with diagnostic applications. "At this point, we aren't far enough along to say whether this would be pivotal data," said Don Black, global head of R&D for medical diagnostics at GE Healthcare Biosciences.
"The primary use for this sort of thing in the past has been diagnosis, but what we're trying to do with all of our diagnostic agents is to move toward disease monitoring, and as therapeutic companies come up with disease-modifying agents, we think we can help in monitoring patients' progress as well."
Only a day before Woodcock's comments, GE and Eli Lilly said they had signed a deal in which GE would gain access to Lilly's molecular libraries to search for compounds useful for developing targeted diagnostic imaging agents for Alzheimer's, while Lilly would be able to use these diagnostic agents in pursuit of therapeutics. According to a GE spokesperson, that agreement is unrelated to the current Roche-GE deal, which may well lead to the use of PET scanning in the stratification of clinical trials and personalized treatment in Alzheimer's disease.
This deal also comes about one year after GE Global Research partnered with Celera to develop imaging agents related to malignancies.
But Woodcock's comments may not have influenced the companies' timing. "I don't think [the use of imaging technologies in drug development] is stimulated by the FDA push toward it," Burns said. "I think it's more that the FDA and the industry are evolving along those lines in the same manner."
Instead, said Burns, Roche is finally starting to see the fruits of a long-term investment. "Using GE's technology, we think we'll be able to see a direct effect on the magnitude of benefit on the amyloid plaque," he said. "We haven't been able to do that before." Previously, patient symptoms were the only means of monitoring efficacy, he said.
"The primary use for [PET scanning in Alzheimer's] in the past has been diagnosis, but what we're trying to do with all of our diagnostic agents is to move toward disease monitoring, and as therapeutic companies come up with disease-modifying agents, we think we can help in monitoring patients' progress as well," said Black.
The companies declined to disclose financial details, as well as the status of the drug's development, other than to say that it is in an early stage.
The detection of amyloid plaques does not trigger a diagnosis of any sort, and plaque status is not considered a surrogate endpoint by the FDA.
But the use of PET scanning in the clinic suggests that the field is moving that way. In September, the Centers for Medicare and Medicaid Services opened fluoro-D-glucose PET scanning for reimbursement when it is used in the diagnosis and treatment of mild cognitive impairment and early dementia in elderly patients.
PIB, the GE PET-imaging agent, is a ligand capable of attaching directly to beta-amyloid plaques, allowing their direct visualization and periodic monitoring, Black said.
GE licensed PIB from the University of Pittsburgh in late 2003, according to a company statement.
In addition to possibly allowing Roche to more easily evaluate its Alzheimer's treatment and allowing GE to further develop its PIB technology, the collaboration might eventually "bring products to market that will give [clinicians] a lot more information regarding who might benefit from these products, and the magnitude of their benefit during the course of treatment," Burns said. "That's very exciting."
Burns declined to speculate, however, on whether PET scanning would be useful to clinicians seeking to guide treatment of Alzheimer's patients with Roche's unnamed drug, should it come to market. He also said he did not believe that post-market collaboration between the companies, such as the use of GE's PET-imaging agent to guide treatment, was "within the range of this agreement."
No plans exist to use the imaging agent as a companion diagnostic to the Roche drug, said Black.
About 4 million Americans have been diagnosed with Alzheimer's disease, according to the US National Institute of Mental Health.
Asked whether Roche would be interested in similar collaborations involving other drugs, Burns said the company was always on the lookout for innovation, and would seek partnerships with other firms when those opportunities present themselves.
"We're always open" to similar collaborations, said GE's Black. "But that's probably all that I can say."
George Mills, director of the medical imaging and radiopharmaceutical drug products unit at the FDA's Center for Drug Evaluation and Research, told Pharmacogenomics Reporter's sister publication BioCommerce Week in April that it may take as long as five years for the agency to become comfortable enough with imaging data to systematically evaluate it during the regulatory process. It may be even longer for imaging data to become part of the drug-development and approval process.
GE Healthcare leads the PET/CT scanner market, followed by Siemens and Philips Electronics, respectively, Antonio Garcia, research manager for medical imaging for Frost and Sullivan, told BioCommerce Week.
Approximately 700,000 PET scans were conducted in the US in 2003, with about 7 percent of those performed in cardiology and neurology, according to the Des Plaines, Ill.-based research firm IMV Medical Information Division.
— Chris Womack ([email protected])