FDA letter supports use of new alpha-synuclein assay in trials
Tool may help select patients, improve efficiency, in Parkinson's studies
The U.S. Food and Drug Administration (FDA) is encouraging scientists and drug developers to use an alpha-synuclein seed amplification assay (synSAA) to improve the development and efficiency of clinical trials seeking to delay or prevent the development of Parkinson’s and other neurodegenerative diseases that share toxic clumps of that protein as a causing mechanism.
In a letter of support to C-Path’s Critical Path for Parkinson’s, a public-private partnership to accelerate the path to approval of new Parkinson’s treatments, the FDA recommends the assay be used to select patients for clinical trials. The FDA letter also encourages sharing patient data from clinical trials to build trust in using synSAA as a valuable biomarker for drug development.
To date, Amprion’s SAAmplify-ɑSYN Biomarker Test is the only validated synSAA assay available in the U.S. to improve the diagnosis of Parkinson’s and other synucleinopathies, which have traditionally been diagnosed based on clinical symptoms only. This new tool is expected to help identify Parkinson’s with high accuracy.
Validated in 2023 with data from the ongoing Parkinson’s Progression Markers Initiative (PPMI), a study created by The Michael J. Fox Foundation (MJFF), the assay is able to distinguish different disease subtypes and detect synucleinopathies even before hallmark disease symptoms develop.
“The search for a Parkinson’s biomarker has been a centerpiece of The Michael J. Fox Foundation’s mission-critical work since our earliest days,” Todd Sherer, PhD, the MJFF’s chief mission officer, said in a press release from the nonprofit. “As we continue working urgently toward better treatments and a cure, the FDA’s backing of [syn-SAA] is an important milestone in advancing today’s robust pipeline of Parkinson’s therapies that patients and families urgently need.”
Amprion stated in a separate press release that the company “commends” the FDA’s issuance of the letter.
“We are very pleased with the timing of this FDA support letter given that there are a growing number of disease-modifying drug candidates in clinical development,” said Russell Lebovitz, MD, PhD, Amprion’s CEO and co-founder.
FDA letter is evidence of test’s importance, developer says
Like other synucleinopathies, Parkinson’s is characterized by deposits of abnormal clumps, or aggregates, of misfolded alpha-synuclein, which play a key role in disease progression. These toxic alpha-synuclein aggregates spread in a prion-like manner, meaning that clumps in one brain region can trigger the formation of more clumps in neighboring areas.
Amprion’s assay uses a sample of cerebrospinal fluid (CSF), the clear liquid that surrounds the brain and spinal cord, to detect the presence of the abnormal alpha-synuclein protein, which may help diagnose synucleinopathies with high accuracy.
The test can detect a small amount of misfolded alpha-synuclein in CSF. If present, the abnormal alpha-synuclein will act as a seed that triggers normal alpha-synuclein to clump in the test environment.
SAAmplify builds on SYNTap, Amprion’s seed amplification assay (SAA), and remains the only test available in the U.S. to help in the diagnosis of synucleinopathies in the clinical setting. Testing is ongoing at a single site in San Diego. The company plans to enter the European market by 2025.
This FDA letter shines a bright light on the importance of this test in early detection of neurodegenerative disorders such as Parkinson’s disease and Alzheimer’s disease.
Accumulating evidence shows that SAAmplify can identify Parkinson’s with high specificity and sensitivity at an early stage of the disease in adults who show symptoms or have prodromal manifestations, meaning that both motor and nonmotor symptoms have yet to fully develop. Sensitivity refers to how well a test can identify people with a disease, while specificity is its accuracy in identifying those without the disease.
In Parkinson’s, the evidence to date suggests the assay can be used as a biomarker to detect people who will go on to develop the neurodegenerative disease. That could potentially accelerate clinical trials that seek to develop new therapies, including preventive ones, for Parkinson’s. It also may help to explore whether experimental therapies are inducing the desired biological changes in patients.
“We are continually impressed by the specificity and sensitivity of our test. This FDA letter shines a bright light on the importance of this test in early detection of neurodegenerative disorders such as Parkinson’s disease and Alzheimer’s disease,” Lebovitz said. “Amprion is proud to collaborate with many industry leaders on these trial advancements.”
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