This week we discuss the FDA's approval of Isembyld for SMA, the approval of a gene therapy for MPS IIIA, and the FDA's Center for Devices and Radiological Health new Rare Disease Impact Initiative.

Approval of Isembyld for Spinal Muscular Atrophy

The FDA announced the approval of Isembyld (apitegromab-mstn) to treat patients 2 yrs and older with spinal muscular atrophy who are currently receiving SMN2-targeted therapy.

SMA is a genetic condition in which patients lose spinal muscle function due to a mutation in the SMN1 gene. There are three therapies for this condition: one is a gene therapy that replaces the SMN1 gene, and the other two, significantly cheaper therapies, increase the activity of a backup gene, SMN2, to increase the missing SMN protein.

This new drug is an add-on therapy to those two latter therapies that target SMN2.

It will be interesting to see how payers and physicians decide where this fits, particularly when you're treating a relatively small patient population with very expensive therapies.

There's another interesting piece to this approval. Scholar Rock received a pediatric priority review voucher. These vouchers are intended to encourage companies to develop treatments for children, something that historically has been more difficult because pediatric clinical trials can be challenging to conduct. We're seeing pharmaceutical companies increasingly pursue these opportunities.

Gene Therapy Approved for MPS IIIA

The FDA also approved a gene therapy for MPS IIIa, also referred to as Sanfilippo syndrome type A.

MPS IIIa is a devastating disease. These children start out looking very healthy, but as toxic levels of heparin sulfate accumulates in their cells, these children begin a cognitive and behavioural decline that completely disrupts the family.

The results from the study leading to the approval is impressive. Instead of the typical cognitive decline seen in these children, adding gene therapy stabilized or improved their cognitive abilities.

The therapy is priced at $3.9 million for a single treatment. That's obviously an enormous dollar amount, and payers generally don't like paying that kind of cost upfront, even when a one-time therapy could potentially be less expensive over the long term than years of continuous treatment.

It's also an important moment for Ultragenyx. This is their second FDA approval in the last month, and they've established 25 centers capable of delivering the gene therapy, with plans to expand that to 40.

So this isn't just about getting therapy approved. It's also about building the infrastructure to actually get these therapies to patients.

Rare Disease Impact Initiative

The FDA's Center for Devices and Radiological Health (CDHR) introduced its Rare Disease Impact Initiative.

While we tend to focus on drug therapies to manage patients with rare conditions, there are many diseases that rely on medical devices to manage and/or monitor patients. At last count, the FDA listed over 2000 devices that are being used to help people with rare conditions.

The FDA's Rare Disease Impact Initiative is designed to help medical-device developers work more directly with the FDA as they develop products for rare disease populations.

It's another part of the rare disease ecosystem that we think deserves more attention.

Looking Ahead

Several important FDA decisions are coming up.

September 26: Mirum's therapy for fibrodysplasia ossificans progressiva, or FOP.

September 27: Tlevar Therapeutics' therapy for cholangiocarcinoma and Praxis' therapy for SCN2A and SCN8A deficiencies.

September 28: Egetis Therapeutics' orphan drug to treat patients with MCT8 deficiency.

References

FDA approves new SMA drug

https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-first-therapy-target-muscle-loss-spinal-muscular-atrophy

FDA approves gene therapy for MPS IIIA

https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapy-pediatric-patients-sanfilippo-syndrome-type

CDRH Rare Disease Impact Initiative

https://www.fda.gov/about-fda/center-devices-and-radiological-health/cdrh-rare-disease-impact-initiative

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This educational program, hosted by Dawn Laney, MS, CGC, CCRC, Genetic Counselor and Program Leader for the Lysosomal Storage Disease Center at Emory University, and Staci Kallish, DO, Associate Professor of Clinical Medicine in the Division of Translational Medicine and Human Genetics at the University of Pennsylvania, examines how best to respond to patients concerns about how their Fabry disease, and its comorbidities, are managed. This program features a dialogue between patients who express their unmet needs, while two renowned Fabry disease experts translate these challenges into actionable clinical strategies.

Topic covered in this video segment is how well the medical team works together and understands Fabry disease.

This educational program is a non-CME activity made possible by an unrestricted grant from Amicus Therapeutics

Faculty
Dawn Laney, MS, CGC, CCRC
Genetic Counselor, Division of Medical Genetics
Program Leader, Lysosomal Storage Disease Center
Emory University School of Medicine
Disclosures
Consulting agreements: Amicus Therapeutics, Chiesi, Sanofi
Member: North American and International Fabry Registry Boards

Staci Kallish, DO
Associate Professor of Clinical Medicine
Division of Translational Medicine and Human Genetics
Perelman School of Medicine, University of Pennsylvania
Disclosures
Research grants: ashibio, Astellas Pharma, , Amicus Therapeutics
Idorsia Therapeutics, Incyte , Ipsen, and Sanofi
Consulting: Amicus Therapeutics, Sanofi
Advisory board: Amicus Therapeutics, Intrabio, Sanofi
Speaking honoraria: Amicus Therapeutics, Astellas, Sanofi

Learning Objective
Upon completion of this program, participants will be able to:
• Orchestrate a cohesive, multidisciplinary team approach to care.

27 0

This educational program, hosted by Dawn Laney, MS, CGC, CCRC, Genetic Counselor and Program Leader for the Lysosomal Storage Disease Center at Emory University, and Staci Kallish, DO, Associate Professor of Clinical Medicine in the Division of Translational Medicine and Human Genetics at the University of Pennsylvania, examines how best to respond to patients concerns about how their Fabry disease, and its comorbidities, are managed. This program features a dialogue between patients who express their unmet needs, while two renowned Fabry disease experts translate these challenges into actionable clinical strategies.

Topic covered in this video segment is whether the risk of kidney failure is being properly addressed by medical teams.

This educational program is a non-CME activity made possible by an unrestricted grant from Amicus Therapeutics

Faculty
Dawn Laney, MS, CGC, CCRC
Genetic Counselor, Division of Medical Genetics
Program Leader, Lysosomal Storage Disease Center
Emory University School of Medicine
Disclosures
Consulting agreements: Amicus Therapeutics, Chiesi, Sanofi
Member: North American and International Fabry Registry Boards

Staci Kallish, DO
Associate Professor of Clinical Medicine
Division of Translational Medicine and Human Genetics
Perelman School of Medicine, University of Pennsylvania
Disclosures
Research grants: ashibio, Astellas Pharma, , Amicus Therapeutics
Idorsia Therapeutics, Incyte , Ipsen, and Sanofi
Consulting: Amicus Therapeutics, Sanofi
Advisory board: Amicus Therapeutics, Intrabio, Sanofi
Speaking honoraria: Amicus Therapeutics, Astellas, Sanofi

Learning Objective
Upon completion of this program, participants will be able to:
• Identify and overcome barriers to managing kidney concerns in patients with Fabry disease.

27 0

This educational program, hosted by Dawn Laney, MS, CGC, CCRC, Genetic Counselor and Program Leader for the Lysosomal Storage Disease Center at Emory University, and Staci Kallish, DO, Associate Professor of Clinical Medicine in the Division of Translational Medicine and Human Genetics at the University of Pennsylvania, examines how best to respond to patients concerns about how their Fabry disease, and its comorbidities, are managed. This program features a dialogue between patients who express their unmet needs, while two renowned Fabry disease experts translate these challenges into actionable clinical strategies.

Topic covered in this video segment is whether the risk of stroke or heart failure is being properly addressed by medical teams.

This educational program is a non-CME activity made possible by an unrestricted grant from Amicus Therapeutics

Faculty
Dawn Laney, MS, CGC, CCRC
Genetic Counselor, Division of Medical Genetics
Program Leader, Lysosomal Storage Disease Center
Emory University School of Medicine
Disclosures
Consulting agreements: Amicus Therapeutics, Chiesi, Sanofi
Member: North American and International Fabry Registry Boards

Staci Kallish, DO
Associate Professor of Clinical Medicine
Division of Translational Medicine and Human Genetics
Perelman School of Medicine, University of Pennsylvania
Disclosures
Research grants: ashibio, Astellas Pharma, , Amicus Therapeutics
Idorsia Therapeutics, Incyte , Ipsen, and Sanofi
Consulting: Amicus Therapeutics, Sanofi
Advisory board: Amicus Therapeutics, Intrabio, Sanofi
Speaking honoraria: Amicus Therapeutics, Astellas, Sanofi

Learning Objectives
Upon completion of this program, participants will be able to:
• Identify and overcome barriers to managing heart concerns in patients with Fabry disease.

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This educational program, hosted by Dawn Laney, MS, CGC, CCRC, Genetic Counselor and Program Leader for the Lysosomal Storage Disease Center at Emory University, and Staci Kallish, DO, Associate Professor of Clinical Medicine in the Division of Translational Medicine and Human Genetics at the University of Pennsylvania, examines how best to respond to patients concerns about how their Fabry disease, and its comorbidities, are managed. This program features a dialogue between patients who express their unmet needs, while two renowned Fabry disease experts translate these challenges into actionable clinical strategies.

The topic covered in this video clip is symptoms that patients believe are not being well managed by their medical team.

This educational program is a non-CME activity made possible by an unrestricted grant from Amicus Therapeutics.

Faculty
Dawn Laney, MS, CGC, CCRC
Genetic Counselor, Division of Medical Genetics
Program Leader, Lysosomal Storage Disease Center
Emory University School of Medicine
Disclosures
Consulting agreements: Amicus Therapeutics, Chiesi, Sanofi
Member: North American and International Fabry Registry Boards

Staci Kallish, DO
Associate Professor of Clinical Medicine
Division of Translational Medicine and Human Genetics
Perelman School of Medicine, University of Pennsylvania
Disclosures
Research grants: ashibio, Astellas Pharma, , Amicus Therapeutics
Idorsia Therapeutics, Incyte , Ipsen, and Sanofi
Consulting: Amicus Therapeutics, Sanofi
Advisory board: Amicus Therapeutics, Intrabio, Sanofi
Speaking honoraria: Amicus Therapeutics, Astellas, Sanofi

Learning Objectives
Upon completion of this program, participants will be able to:
• Recognize the real-world burdens facing Fabry patients and implement strategies to alleviate them.

26 0

This educational program, hosted by Dawn Laney, MS, CGC, CCRC, Genetic Counselor and Program Leader for the Lysosomal Storage Disease Center at Emory University, and Staci Kallish, DO, Associate Professor of Clinical Medicine in the Division of Translational Medicine and Human Genetics at the University of Pennsylvania, examines how best to respond to patients concerns about how their Fabry disease, and its comorbidities, are managed. This program features a dialogue between patients who express their unmet needs, while two renowned Fabry disease experts translate these challenges into actionable clinical strategies.

Topics covered include 1) symptoms that patients believe are not being well managed by their medical team, 2) whether the risk of stroke or heart failure is being properly addressed by medical teams, 3) whether the risk of kidney failure is being properly addressed by medical teams, and 4) how well the medical team works together and understands Fabry disease.

This educational program is a non-CME activity made possible by an unrestricted grant from Amicus Therapeutics


Faculty
Dawn Laney, MS, CGC, CCRC
Genetic Counselor, Division of Medical Genetics
Program Leader, Lysosomal Storage Disease Center
Emory University School of Medicine
Disclosures
Consulting agreements: Amicus Therapeutics, Chiesi, Sanofi
Member: North American and International Fabry Registry Boards

Staci Kallish, DO
Associate Professor of Clinical Medicine
Division of Translational Medicine and Human Genetics
Perelman School of Medicine, University of Pennsylvania
Disclosures
Research grants: ashibio, Astellas Pharma, , Amicus Therapeutics
Idorsia Therapeutics, Incyte , Ipsen, and Sanofi
Consulting: Amicus Therapeutics, Sanofi
Advisory board: Amicus Therapeutics, Intrabio, Sanofi
Speaking honoraria: Amicus Therapeutics, Astellas, Sanofi

Learning Objectives
Upon completion of this program, participants will be able to:
• Recognize the real-world burdens facing Fabry patients and implement strategies to alleviate them.
• Identify and overcome barriers to managing heart concerns in patients with Fabry disease.
• Identify and overcome barriers to managing kidney concerns in patients with Fabry disease.
• Orchestrate a cohesive, multidisciplinary team approach to care.

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Jenny McCue, Vice President of Global Research and Clinical Development at the Myasthenia Gravis Foundation of America (MGFA), discusses research highlights to be presented at the upcoming 2026 MGFA Scientific Session being held September 29th in Orlando, FL.

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Amy Waldman, MD, pediatric neurologist and Medical Director of the Leukodystrophy Center at the Children’s Hospital of Philadelphia, discusses the approval of zilganersen to treat patients with Alexander disease.

Alexander disease is a rare leukodystrophy that impairs neuronal signalling. Most cases of Alexander disease begin before age 2 and are described as the infantile form. Signs and symptoms of the infantile form typically include an enlarged brain and head size, seizures, stiffness in the arms and/or legs, intellectual disability, and developmental delay. Alexander disease is also characterized by abnormal protein deposits known as Rosenthal fibers. These deposits are found in specialized cells called astroglial cells, which support and nourish other cells in the central nervous system.

Zilganersen is an antisense oligonucleotide that binds to RNA and is designed to inhibit production of excess glial fibrillary acidic protein (GFAP) that accumulates as a result of pathogenic variants in the GFAP gene. It is the first and only disease modifying therapy approved for this indication.

The approval is based on positive results from a global, multicenter, randomized, double-blind, controlled, multiple-ascending dose (MAD) phase 1-3 study (NCT04849741) that enrolled 54 participants with Alexander disease.

The study met its primary endpoint in individuals 5 years of age and older, with zilganersen 50 mg demonstrating statistically significant and clinically meaningful stabilization of gait speed as assessed by the 10-Meter Walk Test (10MWT) compared to control at week 61. The treatment also demonstrated a favorable safety and tolerability profile, with most adverse events being mild or moderate in severity.

Alexander disease faces a unique challenge to getting on newborn screening panels. Although the disease does typically present in young children, GFAP accumulation may not be high enough to detect at birth. Dr. Waldman explains that research is still being done to determine when the earliest possible diagnosis can be made. However, she highlights the following red flag symptoms that may point to central nervous system involvement and may warrant genetic testing: in younger children these include gross motor and developmental delays, seizures, and in older children, these include more mild symptoms such as hypernasal speech, speech delay, vomiting, and gait imbalance.

For more information on the approval, visit https://ir.ionis.com/news-releases/news-release-details/zanvastrotm-zilganersen-approved-fda-first-and-only-disease

To learn more about Alexander disease and other rare neurological conditions, visit https://checkrare.com/diseases/neurology-nervous-system-diseases/

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Jenny McCue, Vice President of Global Research and Clinical Development at the Myasthenia Gravis Foundation of America (MGFA), discusses research highlights to be presented at the upcoming 2026 MGFA Scientific Session being held September 29th in Orlando, FL.

Myasthenia gravis (MG) is a chronic autoimmune neuromuscular disease characterized by weakness of the skeletal muscles. It mostly develops in adults but children can also develop this rare condition. Common symptoms include weakness of the muscles that control the eye and eyelid, facial expressions, chewing, talking, and swallowing. The condition results from a defect in the transmission of nerve impulses to muscles usually due to the presence of antibodies against the acetylcholine receptor at the neuromuscular junction. The exact reason this occurs is not known.

MGFA is a patient advocacy organization focused on driving research through funding and connecting scientists and physicians working on MG around the world. The MGFA works in funding pilot grants for early phase research, as well as foundation and fellowship grants that fund clinical and translational research. This year the organization is launching three new series of grants focused on seronegative, biomarkers, and pediatrics. Visit the MGFA website for more information on grant funding.

The MGFA Scientific Session brings together researchers, physicians, and investigators to discuss the newest science in myasthenia gravis. The MGFA Scientific Session will take place Tuesday, September 29, 2026 during the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) Annual Meeting.

This year’s session will host the most research seen at the event yet, which Ms. McCue says speaks to the growing number of the MG community as well as study areas within the disease. The session is organized around some of these areas that cover the full timeline of the MG journey.

Keynote speaker Dr. Sarah Hoffmann will start the day, then the first section of presentations will focus on biomarkers, basic science, and diagnostics. The story then transitions to the second and largest area of research, therapeutics and clinical trials. The third section will focus on seronegative MG. Then, the meeting closes out with “hot topics” of patient care, outcomes, digital health and real world evidence. Complementing the day, poster sessions will run throughout the event.

Ms. McCue highlights the importance of healthcare practitioners staying up to date with the latest research. Key areas of focus include the need to be aware of early and more accurate diagnosis, treatment that matches a more individual experience with MG, and better monitoring and access to tools.

To learn more about MG and other rare musculoskeletal conditions, visit https://checkrare.com/diseases/musculoskeletal-diseases/

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