Putting you in the heart of the rare community – National PKU Alliance
Estimated reading time: 6 minutes
Patient advocacy groups deliver their top three unmet needs and main asks of industry to best serve their rare community. This week’s insights come from Catherine Warren, executive director of National PKU Alliance
National PKU Alliance (NPKUA) is a registered not-for-profit (501(c)(3)) organisation that was founded in 2008 after parents and grandparents formed a working group to create the beginnings of NPKUA to unite local and regional groups. Since the inception in 2008, NPKUA remains steadfast in its support of research endeavours through regular communications with emerging industry and academic leaders at the forefront of PKU research and investing in the NPKUA Grant Program and PKU Patient Registry. The organisation has supported numerous fundraising events, conferences, community programmes and affiliate organisations across the United States.
Phenylketonuria (PKU) is a rare, inherited metabolic disease caused by a deficiency of the enzyme phenylalanine hydroxylase (PAH). This enzyme helps to break down the amino acid phenylalanine (Phe), meaning that people with PKU are unable to process Phe, causing a toxic buildup in the blood and brain. This buildup can cause irreversible damage including neurological effects such as IQ loss, memory loss, seizures, learning disabilities and emotional issues. As a building block of protein, Phe is found in most foods and some artificial sweeteners, so people with PKU need to follow a very restrictive diet low in Phe to reduce its toxic neurologic effects.
What are your top three unmet needs or main asks of industry to best serve your rare ecosystem?
While there are two pharmaceutical treatments currently available, they are not effective for all people with PKU and many still require medical nutritional therapy to manage their blood phenylalanine (Phe) levels. Because of this, there is a need for a great number and variety of treatment options to serve the entire PKU community. Specifically, sapropterin dihydrochloride is an oral medication that requires individuals with PKU to have some residual phenylalanine hydroxylase (PAH) enzyme activity to exhibit a response to this treatment. Individuals with severe forms of PKU likely will not benefit from this medication.
The other available medication, pegvaliase, is currently available for individuals 18 years of age or older in the US and is an injectable drug. This method of administration is inherently more burdensome and is associated with severe side effects, including the risk of anaphylaxis, due to its impact on the immune system. The limitations of these commercially available therapies leave a large number of individuals with only medical nutritional therapy to treat their PKU. Many face significant challenges adhering to the protein-restricted diet given the limited amounts of natural proteins allowed, with the majority of their protein coming from unpalatable Phe-free, amino acid fortified medical foods/formulas. The addition of new treatments to address the entire PKU community that can allow for incorporation of more natural protein sources in the diet would significantly improve the quality of life and outcomes of individuals with PKU.
Ultimately, the PKU community desires a cure for their disease that can be safely administered. Although PKU is not considered to be a life-threatening condition, it demands intensive daily management that places a significant burden on individuals and their families in this community. Many are unable to lower their blood Phe levels within the recommended targeted range. Even in those who strictly adhere to medical nutrition therapy and maintain blood Phe levels within the recommended range often experience symptoms that negatively impact their overall quality of life. While the majority of individuals with PKU are diagnosed during the newborn period to allow prompt treatment implemented shortly after birth, many have still exhibited complications of this disease, such as neurocognitive deficits, psychosocial issues and somatic comorbidities impacting their daily life. A cure for PKU would dramatically change the impact of this disease and lead to improved quality of life and better outcomes for people with PKU and their families.
A cure may also alleviate the symptoms associated with maternal PKU, which occurs when a woman with PKU becomes pregnant and her elevated blood Phe levels cause toxicities to her fetus. Maternal PKU syndrome causes congenital heart defects, microcephaly, intrauterine growth restriction and intellectual disability leading to an increased risk of poor outcomes in babies born to women with PKU. Having a cure for PKU may decrease the risk for the occurrence of maternal PKU syndrome, hopefully leading to more desirable pregnancy outcomes for women with PKU.
While Phe remains a validated and trusted biomarker for managing individuals with PKU, the community has expressed a clear need for additional measures to better capture their symptoms and impact of this disease. Many report experiencing symptoms even when their blood Phe levels are within the recommended range, leading to challenges with determining effectiveness of various PKU treatments and management approaches. Identifying clinical outcome assessment (COA) tools, particularly those that could measure the neurocognitive and psychosocial impacts of PKU, could lead to a better understanding of how to provide more comprehensive care and better outcomes.
Currently, access to pharmaceutical treatments is primarily determined based on their impact on blood Phe levels. Many individuals whose symptoms do not align with their blood Phe measurements may not receive insurance authorisation for payment of that treatment despite receiving benefits from it. If we can identify more sensitive and validated COAs to evaluate the efficacy of new treatments, this could improve access to needed treatments and ultimately improve the quality of life for people living with PKU.
Additionally, the current methods for measuring blood Phe are time-consuming, inefficient and delay clinical care. Currently, blood Phe is measured via a laboratory blood draw or mailed filter papers to a PKU clinic. This delay often causes more infrequent blood Phe testing below what is recommended in the PKU management guidelines. Because monitoring blood Phe levels is a critical component of PKU management, several companies are working to develop an at home Phe monitor to provide results in minutes to more easily track blood Phe. Having a home Phe monitor would dramatically change the management for PKU by reducing clinic visits, enabling more timely management, helping individuals better understand their symptoms in real time, improving data collection for clinical trials and enhancing safety monitoring for maternal PKU.
Connect with Catherine
in the thick of it puts you in the heart of the RARE communities you serve.
To connect with more RARE communities click below.
