By: Rachel Salzman, DVM President & CEO SwanBio Therapeutics
One of the most heartbreaking experiences for a person living with a rare disease is being confronted with a series of inaccurate diagnoses. Unfortunately, this is a common occurrence in the orphan disease space, which is on average a seven-year-long experience fraught with misdiagnoses that leads to patient suffering and wasted healthcare resource utilization. Much of this would be prevented if newborn screening became more widely adopted. Then, when a newborn is screened positive, a suitable treatment plan is initiated. These screening programs could save countless lives every year. Population genetics inform us that there is an emerging gap across inherited diseases. wherein family members are likely carriers of the disease. Here is where kindred analysis/cascade screening plays an essential role.
In the United States and many other countries, newborns are automatically screened for a range of disorders during their first few days of life. The “Master List” for these conditions is contained within the Recommended Uniform Screening Panel, or RUSP, which is maintained via the Department of Health and Human Services. While the RUSP provides guidance/best practices, it is each state’s responsibility to establish and fund its own New Born Screening (NBS) program. There are currently only 34 core and 26 secondary disorders on the RUSP, and there may be as many as 7,000 rare diseases; however, some states screen for far fewer than this number, while others screen for significantly more.
Case study – Impact of NBS & Cascade Screening
A young married father in his 30’s was experiencing progressive spasticity, weakness, and pain in his limbs over the course of several years. He had been to many physicians over the duration of his symptoms without receiving a definitive diagnosis. Understandably, having to deal with a mysterious and progressive neurological disease took a massive toll on his family life, his work life, and his emotional psyche. This man’s sister was pregnant and living in a state that had not yet adopted the adrenoleukodystrophy (ALD) screen. ALD is a severe X-linked disease that manifests in the neurological system, with an incidence of 1:17,000 live births. By complete coincidence, in her final trimester, she moved to an early adopter state that had successfully implanted an ALD screening program.
Her infant son was diagnosed as carrying a mutated ALD gene. In parallel, the family underwent cascade screening, and the uncle was identified as a second-degree relative with the same mutation. He was diagnosed with adrenomyeloneuropathy (AMN), the adult phenotype of ALD. Although there is as yet no cure, proper diagnosis allows his condition to be managed by appropriate treatments, and as new therapies become available, he would be immediately eligible to receive better treatment.
This family now has an answer to the highly distressing mystery. Most importantly, they have received appropriate genetic counseling, which they could immediately integrate into their family planning.
As an effort to broaden the genetic screening panel, ALD, a severe inherited neurological disease was added to the RUSP in 2016 after a 2012 nomination. The advocacy and research communities took a proactive approach to reinforce the importance of incorporating ALD to the screening panel. Stakeholders foresaw the parallel unfolding of the drug development landscape alongside a potential RUSP expansion.
Genetic screening for ALD should enable early and rapid patient identification and help to bring the right therapy to the right patient. We now expect the vast majority of the 4,000,000 babies born in the US each year to be screened for ALD by the time FDA approves a medicine.
Coordination and timing between NBS nomination and drug development are crucial to maximizing a new therapy’s impact and its ability to reach the target patient population. Typical new drug development has a 10-15 year timeframe (rare diseases may be less) while NBS nomination, RUSP designation, and subsequent state-by-state implementation can take 8-10 years to fully implement across all 4 million annual births in the US. Thus it is crucial that NBS nomination and RUSP designation start as early as possible in the drug development cycle to ensure that the drug can have the most significant impact and reach the desired population. Coordination and partnership between key stakeholders (e.g., public health/regulatory agency advocacy groups, biotech companies) could enable broad coverage. The implementation of newborn screening will result in decreased misdiagnosis and significant improvement in patient outcomes.
Biotech companies working alongside patient advocacy groups can play a significant role in adding new diseases to the screening panel. Patient advocacy groups will influence every aspect of the patient journey including screening, diagnosis, and bringing new therapies to market. Continued connectivity can accelerate patient identification and recruitment for clinical trials. Start-ups in the rare disease space should engage advocacy groups early on in the process, as such deliberate actions ultimately serve to benefit all stakeholders.