Qualifying Biomarkers to Support Rare Disease Regulatory Pathways: Focus on Neuropathic MPS

February 29, 2024

Page content provided by: Cure Sanfilippo Foundation, National MPS Society, and The Ryan Foundation

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Speakers at the Feb. 21 “Qualifying Biomarkers to Support Rare Disease Regulatory Pathways” workshop hosted by Reagan Udall Foundation for FDA.

Press Release: Advocacy Groups Join Reagan-Udall Foundation and FDA for Feb. 21 Workshop on Developing Biomarkers to Support Accelerated Approval in Rare Diseases

Workshop Presented Overwhelming Scientific Evidence to Support CSF-HS as a Primary Biomarker in Neuropathic MPS Disorders

Cure Sanfilippo Foundation, National MPS Society, and The Ryan Foundation took part in a pre-competitive workshop on Feb. 21, 2024, convened by the Reagan Udall Foundation with the FDA and multiple drug sponsors to discuss qualification of cerebrospinal fluid-heparan sulfate, (CSF-HS), as a primary biomarker to support accelerated approval in the neuropathic MPS disorders. During the workshop, viewers heard from leader in the field discussing disease pathology, preclinical and clinical data from multiple drug development programs, validated assays used to measure biomarkers, and a panel made up of rare disease experts on the urgency needed to provide access to the accelerated approval pathway in neurodegenerative ultrarare diseases.

“We are asking the FDA for equitable access to the Accelerated Approval pathway. Similar to cancer patients and therapies, which account for nearly all accelerated approvals, children with neuropathic MPS are dying without treatments and suffering immensely in the process. We truly need access now in Sanfilippo syndrome or we are going to lose another generation of our children,” said Cara O’Neill, MD, FAAP, Cure Sanfilippo Foundation.

Global academic medical experts, 20+ year MPS researchers, senior leaders from the U.S. Food and Drug Administration (FDA) Center for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and Research (CBER), highly experienced drug developers, and other specialists came together to discuss MPS neuropathic pathophysiology, animal studies, clinical outcomes from decades of studies, and patient-focused drug development, surrogate endpoints and the accelerated approval pathway. The meeting focused on MPS Subtypes: MPS I, MPS II (Hunter Syndrome), and MPS IIIA, IIIB, IIIC, and IIID (Sanfilippo Syndrome), which all accumulate toxic heparan sulfate in the central nervous system leading to progressive brain injury.

“During my quarter century working in the field of MPS research, this workshop was the most unified, consistent, and impactful presentation of the case of CSF heparan sulfate as a surrogate biomarker in neuropathic MPS disorders. I’ve never been prouder to present as a scientist and to represent as an advocate as I was last week at the Reagan-Udall Foundation for the FDA,” said Matthew Ellinwood, DVM, PhD, National MPS Society.

Over the past several years, the patient community and sponsor companies have seen the collapse of clinical studies that have failed to meet the criteria of the FDA. These ultra rare diseases are low prevalence with substrate deposition (heparan sulfate) in the brain due to single enzyme defects that result in irreversible and progressive brain damage. Reduction of a primary disease activity biomarker, CSF heparan sulfate, has been demonstrated to correlate closely with the reduction of substrate deposition in the brain. Reduction of CSF-HS is reasonably likely to translate to downstream clinical outcomes.

“At least ten companies developing therapies for Sanfilippo syndrome have halted their programs while regulation is struggling to keep up with the science in the field. FDA has the authority, and we now need them to take action in ensuring that transformational science is not being left behind,” said Mark Dant, Volunteer Executive Director, The Ryan Foundation.

Bringing key MPS stakeholders together to share ideas and research findings in a public forum like the Reagan-Udall Foundation provides the opportunity to have focused and productive discourse to find urgently needed solutions and advance therapies that will improve the lives of those impacted by neuropathic MPS.

“Qualifying Biomarkers to Support Rare Disease Regulatory Pathways” workshop focused on how the accelerated approval pathway is the most appropriate regulatory framework for evaluating treatments in the context of neuropathic MPS diseases. Clinicians, scientific researchers, drug developers, and patient advocates provided confirmatory science that characteristics CSF-HS as a primary disease activity biomarker can drive drug development programs. This path for evidence of effectiveness to support accelerated approval based on reduction of substrate accumulation is outlined in the FDA 2020 Rare Disease Single Enzyme Defect with Substrate Deposition Guidance.

Dr. Cara O’Neill at the Feb. 21, 2024, meeting

Dr. Cara O’Neill speaking during the afternoon session of the Reagan Udall Foundation meeting.

 Morning Session
Afternoon Session

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