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Mindful of the babies
COLOGNE, Germany—Targeted toward reversing the fate of oxygen-deprived newborns presenting with cerebral palsy (CP) and similar symptoms, InfanDx AG has been awarded a €1-million research grant from Germany’s Federal Ministry of Education and Research for a joint project to develop a companion diagnostic based on metabolomic biomarkers.
The company already has its HypoxE-test in late-stage development, but that test aims at identifying whether a newborn is affected by neonatal encephalopathy, while the new companion diagnostic would be used to predict if an identified newborn is likely to benefit from neuroprotective hypothermia treatment. InfanDx will take the lead with researchers from the University Hospital Essen, Clinic for Pediatrics I and Furtwangen University.
“We are honored to receive this grant, which is an important recognition of our current and future development programs aimed at helping newborns avoid lifelong disability,” says Ron Meyer, CEO of InfanDx.
Infants who have experienced an oxygen deficit during delivery (asphyxia neonatorum) can develop neonatal encephalopathy, which may result in lasting brain damage and lifelong disability, Meyer explains. An effective therapy using hypothermia exists and can limit or even prevent permanent brain damage.
However, only about 50 percent of infants affected by neonatal encephalopathy clearly benefit from this burgeoning therapy, he notes. The key is in knowing which infants to treat, and that is where the new diagnostic test comes in. Developing a diagnostic test based on metabolomic biomarkers can differentiate infants who will likely respond to hypothermia treatment from those who likely will not, per Meyer. Non-responders will be spared an ineffective therapy and can receive appropriate alternative treatment in the future in order to achieve maximum neuroprotection.
“Neonatal encephalopathy due to a hypoxic event or asphyxia during delivery is the prime single cause of cerebral palsy,” he tells DDNews. “While CP is a common outcome for encephalopathy, particularly moderate to severe encephalopathy, other outcomes may include a whole range of motoric and cognitive impairments, developmental delays, visual or hearing impairment.”
“In our core technology, we use metabolomics-research to identify biomarkers for different diseases,” Meyer explains. “Our most advanced product candidate, the HypoxE-test, is based on a combination of biomarkers we identified to diagnose acute adverse events in the brain resulting from hypoxic brain injury during birth. Using a combination of only four metabolite biomarkers, we can reliably identify newborns affected by neonatal encephalopathy from a small blood sample.”
Therapeutic hypothermia “has a low level of adverse long-term effects, [but] it is very stressful for an infant and includes three days of sedation,” Meyer says. “With our approach, patients who are identified as non-responders can receive alternative treatments, which are currently under development, and which may be a better choice for these individuals.
“This aspect of very early stratification of patients may be the most exciting part, as it would often allow us to better focus clinical study designs for treatments where an acute cerebral event plays a role. Cost savings and more significant outcome data could be a major benefit.”
For the InfanDx HypoxE-Test, the company has already concluded recruitment of its second clinical trial for the identification of newborns affected by encephalopathy after hypoxia.
“In our first study, our InfanDx HypoxE-test showed already a specificity and sensitivity well over 90 percent,” Meyer comments. “We are planning to publish the detailed results soon. Data for the therapy response-stratification still needs to be obtained, of course. But we have preliminary test results from other studies that suggest our approach has a good chance of functioning well.”
Both of these clinical trials are a valuable resource for the development of the companion diagnostic, because the company can use frozen blood samples from the first trial to examine the patients’ metabolic profiles to differentiate hypothermia responders and non-responders.
“As we do not need to initiate a new study for this, our approach is particularly effective, and we expect data for a potential application in humans much faster than usual,” Meyer says. “We are currently still conducting follow-up examinations of study participants on their health status at more than two years of age.
“Using metabolomics is an innovative approach to detect brain damage and manage treatment decisions,” concludes Dr. Hans-Peter Deigner, dean of the Faculty of Medical and Life Sciences at Hochschule Furtwangen University and co-founder of InfanDx. “This also emphasizes the wide applicability of metabolomics in modern diagnostics.”