FDA Expanded Approval of Imiglucerase Expands Treatment Options for Type 3 Gaucher Disease

The FDA has expanded the approved indication for imiglucerase (Cerezyme; Genzyme) to include the treatment of non-central nervous system (CNS) manifestations of Gaucher disease type 3 in adults and pediatric patients. This regulatory milestone marks the first time any therapy has received FDA approval specifically for this indication, addressing a long-standing unmet need in this rare lysosomal storage disorder.¹

Gaucher disease is a genetic disorder due to mutations that result in reduced activity of the enzyme glucocerebrosidase (GCase), resulting in the accumulation of glucocerebroside in macrophages and various systems. Although type 1 Gaucher disease, the most prevalent form, does not involve the CNS, type 3 Gaucher disease is characterized by slowly progressive neurological manifestations, along with the visceral, hematologic, and skeletal complications that are common to all types.¹

Imiglucerase’s Mechanism and Historical Context

Imiglucerase is a recombinant human GCase that acts as an enzyme replacement therapy (ERT) with the intention of complementing the deficient GCase enzyme and decreasing substrate accumulation within target cells. Initially approved by the FDA in 1994 for non-CNS manifestations of type 1 disease, it has remained a mainstay in the treatment of Gaucher disease for several decades.² Traditionally, its development came after the Ceredase era, which was a placental-derived GCase with equivalent or superior efficacy.³

Although Imiglucerase has been used off-label in patients with type 3 disease and approved for this use in Europe for years, its formal FDA approval for type 3 non-CNS symptoms represents a pivotal regulatory shift with important implications for prescribing, coverage, and clinical certainty.⁴

Evidence Supporting the Expanded Indication

The FDA’s choice was largely based on extensive observational data collected in the International Collaborative Gaucher Group Gaucher Disease Registry (NCT00358943)⁵, which documented real-world outcomes in hundreds of patients treated with imiglucerase. Analyses of the registry data demonstrated that patients with both types 1 and 3 Gaucher disease experienced significant improvements in key clinical end points, including increases in hemoglobin and platelet counts, reductions in liver and spleen volumes, and improvements in growth parameters for pediatric patients.¹

In those with type 3 disease, these results are particularly noteworthy, as they show efficacy in the systemic symptoms of the disease, which can drive morbidity even in the absence of CNS efficacy. Observational studies included more than 100 patients with type 3 disease, showing improvements in hematologic and visceral symptoms after approximately 2 years of treatment.¹

Beyond registry analyses, earlier clinical development—such as phase 3 comparisons of Imiglucerase versus predecessor therapies—established its effectiveness in improving hematologic parameters and organ volumes in Gaucher disease.⁶ These foundational studies supported its long-standing role in type 1 disease and provided context for broader use.

Conclusion

Although ERT does not penetrate the blood-brain barrier and therefore does not impact the neurologic progression of type 3 Gaucher disease, this FDA approval is a major milestone in the management of the symptoms of patients suffering from this condition. Research is ongoing to evaluate adjunctive and new treatments for the CNS manifestations and other unmet needs in those with Gaucher disease.⁷

The expanded Imiglucerase approval stands as a testament to the cumulative value of long-term registry data and real-world evidence in informing regulatory decisions for rare diseases and may serve as a model for future indications across similar disorders.

REFERENCES

1. Lobo A. Cerezyme becomes 1st FDA-approved therapy for type 3 Gaucher. Gaucher Disease News. Published January 20, 2026. Accessed January 26, 2026. https://gaucherdiseasenews.com/2026/01/20/cerezyme-becomes-1st-fda-approved-therapy-type-3-gaucher/

2. Search Orphan Drug Designations and Approvals. FDA. Accessed January 26, 2026. https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=62491&

3. Protocol RC 91-0110: An Evaluation of the Safety and Effectiveness of Recombinant, Human, Macrophage-Targeted β-Glucocerebrosidase. Accessed January 26, 2026. https://www.sanofi.com/assets/dotcom/content-app/clinical-studies/pharma/Letter-I/RC-91-0110_summary.pdf

4. Cerezyme® (imiglucerase) – Expanded indication. Accessed January 26, 2026. https://business.optum.com/content/dam/noindex-resources/business/support-documents/clinical-updates/clinicalupdate-cerezyme-011326.pdf

5. International Collaborative Gaucher Group (ICGG) Gaucher Disease Registry & Pregnancy Sub-registry. ClinicalTrials.gov identifier: NCT00358943. Updated January 6, 2026. Accessed January 26, 2026. https://clinicaltrials.gov/study/NCT00358943

6. Deegan PB, Cox TM. Imiglucerase in the treatment of Gaucher disease: a history and perspective. Drug Des Devel Ther. 2012;6:81-106. doi:10.2147/DDDT.S14395

7. Cerezyme. European Medicines Agency. Accessed January 26, 2026. https://www.ema.europa.eu/en/medicines/human/EPAR/cerezyme