Newborn screening is gaining prominence across the biopharma and healthcare industries amid efforts to detect and treat disease as early as possible. With projections that there could be as many as 60 breakthrough cell and gene therapies approved by the FDA over the next 10 years, the race is on to bring newborn screening practices up to speed.
Companies with advanced therapies to treat genetic diseases work with healthcare systems and advocacy organizations globally to support newborn screening for certain conditions, such as spinal muscular atrophy. However, states in the U.S. currently screen for just 31 to 76 of the hundreds of severe, childhood genetic diseases that have available treatments.
“The federal recommendation is that 35 core genetic disorders are screened for in all newborns, but the actual screening performed varies from state to state,” says Stephen Kingsmore, president and CEO of Rady Children's Institute for Genomic Medicine (RCIGM) where he leads a team of scientists, physicians and researchers who are pioneering the use of rapid Whole Genome Sequencing to enable precise diagnoses for critically ill newborns.
Catherine Nester, vice president of physician and patient strategies at Inozyme Pharma, a clinical-stage rare disease biopharma company, notes that while California screens for 80 genetic and congenital disorders, Arizona, which is one of a small number of states to sign newborn screening laws, screens for only 31.
"The big reason for all of us is to try to get this program out there and broadly available as quickly as possible."
Vice president of physician and patient strategies, Inozyme Pharma
“One of the big issues is that there's just so many diseases that aren't being tested for at all, and even for the ones that are, it's very haphazard across states,” Nester says.
In an effort to address this inconsistency and ensure newborns across the country are screened more widely for genetic disorders, RCIGM has teamed up with a consortium of pharmaceutical, biotechnology and informatics companies to develop a newborn screening test using rapid whole genome sequencing for 388 genetic diseases.
According to Kingsmore, the test, called BeginNGS (Newborn Genomic Sequencing), involves screening, diagnosis, virtual acute management guidance and acceleration of clinical trials of new drugs.
Clinical trials for BeginNGS are slated to start in the U.S. later this year and, he says, a manuscript that describes the results in over 450,000 subjects will “soon be published.”
The test was developed in collaboration with Alexion, AstraZeneca’s Rare Disease group; sequencing and array solutions company Illumina; TileDB, an open-source, cloud-native storage engine; Fabric Genomics, which has designed an AI platform for NGS analysis, interpretation and clinical reporting; and Genomenon, which uses rWGS to diagnose and identify treatment options for genetic conditions before symptoms begin.
Addressing a life-threatening deficiency
Another key member in the consortium is Inozyme Pharma, which is conducting early stage clinical trials of INZ-701 in adult patients with ENPP1 deficiency, a progressive condition associated with generalized arterial calcification of infancy (GACI). GACI, a rare and often fatal neonatal disorder, is characterized by arterial calcifications in the medium and large arteries. Between 45-50% of infants with ENPP1 deficiency die within six months of birth.
For patients who survive infancy, the disease still progresses, causing long-term and complex health issues such as rickets and a rare gene deficiency that leads to low levels of PPi, which is essential for preventing harmful soft tissue calcification and regulating bone mineralization.
Inozyme is hoping to have its pediatric program up and running this year and that would include infants.
“We are very excited about the collaboration between Inozyme and Rady Children's newborn screening program, because early detection, diagnosis, and intervention is absolutely vital to saving the lives of babies affected by GACI and to improving the quality of life of those same children as they grow up,” says Christine O’Brien, co-president of nonprofit organization GACI Global and a parent of two children with GACI.
Inozyme and GACI Global have been collaborating since 2018, after meeting at the Global Genes Rare Patient Advocacy Summit in San Diego, Calif.
“We have a free genetic testing program, but that requires a physician to suspect the disease,” Nester says. “The work with RCIGM came about because we are planning our infant study with our treatment, and waiting two to three weeks to get a genetics report back to get a critically ill baby into the study wasn’t good enough.”
Through the RCIGM screening program, sequencing of critically ill newborns can be done in a matter of days to determine what’s wrong with the baby.
“So, I got connected to Dr. Kingsmore and his team to see how they could help us with the study, which led to us joining the consortium,” she adds.
Although the collaboration started to accelerate turnaround on genomics, it led Nester to wonder: If sick babies could be screened, why not screen for genetic disease in every baby?
“The idea with the screening is it will be across the board, since you won't know necessarily if a baby has a rare disease when they're born,” she says.
Advancing science through screening
The BeginNGS pilot program includes birthing hospitals throughout the U.S. and abroad. Blood-spot samples will be collected at the time of birth and sent to a laboratory where whole genome sequencing will be performed. When a positive screening result is detected, a confirmatory diagnostic test will be completed before a result is returned to the ordering physician, who will then be provided with guidance on appropriate medical management, including all available treatments.
Kingsmore will chair an executive council for the consortium, which will include Tom Defay, deputy director, diagnostics, Alexion, AstraZeneca Rare Disease, as deputy chair and a representative of consortium members.
“Consortium members will also appoint representatives to serve on the Consortium Advisory Council based on membership level,” Kingsmore says. “Founding members will each appoint two individuals to the CAC, and affiliates and community partners will each appoint one individual to the CAC. Finally, there will be around 10 working groups that oversee the day-to-day activities of the consortium.”
"Each year we will increase the number of disorders screened, refresh the virtual management guidance system, and increase the breadth of variants tested.”
President and CEO, Rady Children’s Institute for Genomic Medicine
The consortium’s goals for 2022 are to publish its prototype and proof of concept, have a CLIA-compliant BeginNGS, and start the first prospective clinical trial.
“For 2023, our milestones are to expand the clinical trial to at least two other sites and enroll 2,000 newborns,” Kingsmore says. “For 2024, our milestone is to enroll 20,000 newborns and we aim to enroll 200,000 newborns by 2026. Each year we will increase the number of disorders screened, refresh the virtual management guidance system, and increase the breadth of variants tested.”
Nester says one of the early criteria of the screening program is that the disease has a therapeutic treatment or it’s a disease where some sort of early intervention can make a difference in the infant’s life.
It is a far-reaching consortium, Nester says, and everyone at the table is there for a slightly different reason.
“But the big reason for all of us is to try to get this program out there and broadly available as quickly as possible,” she says.