In the early days of his career, a young scientist named Emil Kakkis found himself deep in the world of academic research, working with the renowned Dr. Elizabeth Neufeld. Their focus was on a rare genetic disease, MPS I, caused by a missing enzyme. With dedication, he and Dr. Neufeld managed a breakthrough: they produced the enzyme and successfully treated dogs with MPS I. Yet, despite this progress, there was no clear pathway to bring the treatment to human patients. The project, on the verge of being shelved, seemed destined to become another entry in a scientific journal, rather than a life-altering therapy.
Then, at a critical moment, he met Mark and Jeanne Dant, who introduced him to their five-year-old son, Ryan, who was living with MPS I. “At that moment, the science became real,” said Dr. Kakkis. “It became personal, not just academic.”
What followed was a hard-fought journey, powered by donations and dreams. Over time, their project gathered momentum, ultimately capturing the attention of biotech company BioMarin. Thanks to their backing, the therapy reached the finish line, and on February 13, 1998—what would become Ryan’s “lucky day”—he received the first enzyme replacement therapy (ERT). It was a treatment that would not only change his life but would allow him to thrive: Ryan grew up, got his driver’s license, graduated from high school, went to college, and eventually married. Today, 26 years later, Ryan still benefits from that very therapy.
Inspired by this success, Dr. Kakkis’s mission took on new life. At BioMarin, he pursued treatments for other MPS disorders, such as MPS VI, which included collaborating with Dr. Hopwood to develop Naglazyme after overcoming significant manufacturing challenges. Next, they worked on Vimizim for Morquio, pushing past initial beliefs that the disease was limited to bones to address its effects throughout the body. Later, at Ultragenyx, he led efforts to produce Mepsevii for MPS VII and saw it approved. Most recently, his team at Ultragenyx took on a gene therapy project for MPS IIIA from Abeona, moving the therapy toward a potential FDA approval that could offer the first treatment for Sanfilippo syndrome.
“Witnessing the transformation of the MPS Society from one of pure patient support to one of treatment access and policy has been exciting to see,” said Dr. Kakkis, “Now the next phase could bring more decisive single treatments for MPS diseases, and more hope for untreated families to finally be treated for the first time.”
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The National MPS Society is pleased to share an update on RGX-121, an investigational gene therapy for MPS II (also known as Hunter Syndrome), from REGENXBIO!
“A potential one-time treatment that can allow these boys to exceed the natural history of this disease in their neurocognitive development, as well as the ability to remain off enzyme replacement therapy for multiple years represents a meaningful option for patients and their families,” said Roberto Giugliani, M.D., Ph.D., Professor, Department of Genetics, UFRGS, Medical Genetics Service, HCPA, Porto Alegre, Brazil. “I continue to be very encouraged by the data supporting RGX-121 and look forward to seeing this program advance towards potential approval for this community.”
You can read a statement from REGENXBIO below, or you can click here to read more about the therapy and its trial results on their website.
After recent successful meetings with the FDA, Denali Therapeutics announced its plan to file for accelerated approval of DNL310 for the treatment of MPSII, also known as Hunter Syndrome.
“We thank CDER for a positive and collaborative discussion and their guidance on CSF HS as a surrogate biomarker, which we see as a significant step towards accelerating development of medicines for individuals and families living with MPS II,” said Carole Ho, MD, Chief Medical Officer of Denali. “This milestone reflects a collective effort across the patient community, academia and industry to communicate the science and advocate for faster paths to effective treatments addressing these devastating rare diseases. We are excited by the potential to deliver a new MPS treatment sooner using the accelerated approval pathway. We also look forward to plans for conversion to full approval following completion of the global Phase 2/3 COMPASS study, and we are grateful for the continued participation and commitment of patients, clinicians, and study teams involved in the tividenofusp alfa clinical studies.”
Denali Therapeutics plans to submit biologics license application (BLA) early in 2025 under the accelerated approval pathway.
Click here to read their full release.
Dearest Sanfilippo Community Members and Allies,
It is with deep sadness that we inform you of the impending liquidation of Allievex. Since the beginning of this drug program with BioMarin (as BMN 250), and then through its acquisition by Allievex (as AX 250), the National MPS Society has been a strong supporter of this drug program and of the Sanfilippo type B community who benefited from its development.
The Allievex treatment was an enzyme replacement therapy using tralesinidase alfa which was delivered weekly directly to the brain via a catheter. This therapy corrected the enzyme deficiency of MPS IIIB patients. The therapy reduced heparan sulfate levels in the brain and spinal cord in preclinical studies, and levels were lowered in the cerebrospinal fluid of treated patients. Especially in the cohort of trial patients who began treatment at a young age, therapy halted the neurodegenerative process and preserved neurological function in patients.
Despite these promising results, the collective efforts of Allievex’s team, and the support of rare disease advocates, researchers, clinicians, families, and allies around the world, the desired regulatory flexibility from the FDA around Accelerated Approval Pathway was not forthcoming during their early discussions with the FDA. They ceased all business operations in October 2023. However, the Allievex team remained hopeful, and pursued additional FDA engagement.
In March of this year, former Allievex employees met with the FDA Center for Drug Evaluation and Research, where the FDA changed course. Allievex was encouraged to file its Biologics License Application for consideration under the Accelerated Approval Pathway. While this was good news, it came too late to rescue the business. Today Allievex announced that they had entered an assignment for the Benefit of Creditors marking the formal liquidation of their assets.
We share in your deep despair over this outcome. Those families and patients who have benefited from this therapy and who now have nothing to look for in the future are an abiding concern to us. We hope for an acquisition that could revive Allievex but are doubtful after so much time. We are grateful that the Allievex program did play a very positive role in the efforts of other MPS treatment developers such as Denali, Ultragenyx, and REGENXBIO to access improved regulatory paths with the FDA, but today’s news still leaves our MPS IIIB community bereft.
The Society remains committed to advocating for and supporting research and treatments for all MPS disorders, and we will continue to communicate any news regarding the future of Allievex as it develops. If you have any questions, please contact Terri Klein at terri@mpssociety.org.
Together, we hope to find a path forward that ensures the best possible outcomes for everyone who is affected by MPS.
Sincerely and with both sadness at this news and hope for the future,
Matthew Ellinwood, DVM, PhD
Chief Scientific Officer
National MPS Society
Click here to read Allievex Founder Thomas Mather’s full statement.
