A recently published paper revealed that the prevalence of ENPP1 deficiency is more than triple the previous estimate. In this blog, co-author and Genomic Science Liaison Lauren Chunn explains why this paper is a must-read for orphan drug developers.
Rare disease drug development has long been hampered by a number of issues, ranging from the lack of an adequate understanding of the pathophysiology and natural history to the lack of incentives to fund the development of orphan drugs for small populations. Accurately estimating the prevalence of a rare disease in a population at a given time is particularly challenging for rare disease populations. If the market is determined to be too small, drug programs may be paused and medical needs may go unaddressed.
ENPP1 deficiency is known to be a rare disease, but arriving at an accurate estimate of the prevalence is challenging. Traditional methods for estimating prevalence rely on clinical data, which can be unreliable for diseases such as ENPP1 deficiency that are difficult to diagnose. One method to overcome these diagnostic challenges would be to base the estimate on genetic, rather than clinical, data. However, the accuracy of this technique relies on the completeness of the knowledgebase of causative variants as well as the number of healthy individuals contained within the population database.
In a recent study published in the Orphanet Journal of Rare Diseases, we collaborated with disease experts from the National Institutes of Health (NIH) and Münster University Children’s Hospital to develop a revised estimate of the genetic prevalence of ENPP1 deficiency. As a result, our data significantly increased the estimated genetic prevalence of the disease – by threefold, suggesting that a significant number of individuals remain undiagnosed.
“This revised estimate underscores the urgent unmet medical need for effective therapies for patients with ENPP1 deficiency.”
– Catherine Nester, Vice President of Physician and Patient Strategies, Inozyme Pharma
To support this study, the Mastermind team performed a comprehensive literature review, updated the population database with the most current clinical data, and performed clinical standard variant interpretation to improve upon the current estimate.
Early Rare Disease Diagnosis is Critical
This revised estimate for ENPP1 deficiency is especially important now that an enzyme replacement therapy (ERT) is being developed and tested in clinical trials. Given the severity of the disease (approximately half of all infants die within the first few months of life), improving early detection of the disease is crucial for appropriate treatment, should the therapy be approved.
This new data underscores the importance of continued research into rare genetic disorders, as a more comprehensive understanding of the genomic landscape of these conditions can inform the development of new treatments—and save patient lives. It’s extremely gratifying to have been part of this work.
Genomenon partners with pharmaceutical companies, such as Inozyme Pharma, to ensure they have access to the genomic intelligence needed to better understand disease mechanisms, more accurately estimate disease prevalence, design clinical trials, and prepare documentation for regulatory approvals.
Contact us to learn more about how we can support your rare disease program.