Amicus Therapeutics announced that Japan's Ministry of Health, Labour and Welfare (MHLW) has approved Pombiliti (cipaglucosidase alfa) + Opfolda (miglustat) for the treatment of adult patients with late-onset Pompe disease (LOPD). The approval marks a significant milestone for patients in Japan living with this rare inherited lysosomal disorder.
"We are delighted that we will now be able to offer a compelling new treatment option to patients living with late-onset Pompe disease in Japan. We are grateful to the MHLW and to Japan's Pompe community, including the patients, families, and physicians who participated in our clinical studies, for their collaboration," said Bradley Campbell, President and Chief Executive Officer of Amicus Therapeutics.
Novel Two-Component Therapeutic Approach
Pombiliti + Opfolda represents an innovative two-component therapy designed to address the underlying enzyme deficiency in Pompe disease. Pombiliti is a recombinant human GAA enzyme (rhGAA) naturally expressed with high levels of bis-M6P (Mannose 6-Phosphate), specifically designed for increased uptake into muscle cells. The therapy is complemented by Opfolda, an oral enzyme stabilizer designed to stabilize the enzyme in the blood and reduce loss of enzyme activity.
The combination therapy consists of cipaglucosidase alfa-atga, a bis-M6P-enriched rhGAA that facilitates high-affinity uptake through the M6P receptor while retaining its capacity for processing into the most active form of the enzyme, paired with miglustat as the oral enzyme stabilizer component.
Clinical Evidence from Landmark PROPEL Study
The MHLW approval was based on clinical data from the Phase 3 pivotal study (PROPEL). PROPEL stands out as the only trial in LOPD to study the real-world population of both ERT-naïve and ERT-experienced participants in a controlled setting, providing comprehensive evidence for the therapy's effectiveness across different patient populations.
Global Market Expansion
With this Japanese approval, Pombiliti + Opfolda has now secured regulatory approval in seven major markets worldwide, including the United States, European Union, United Kingdom, Canada, Australia, Switzerland, and Japan. This broad international approval demonstrates the therapy's potential to address unmet medical needs for LOPD patients globally.
Understanding Late-Onset Pompe Disease
Late-onset Pompe disease is an inherited lysosomal disorder caused by deficiency of the enzyme acid alpha-glucosidase (GAA). Reduced or absent levels of GAA lead to accumulation of glycogen in cells, which is believed to result in the clinical manifestations of Pompe disease. The condition can be severe and debilitating, characterized by progressive muscle weakness throughout the body that worsens over time, particularly affecting skeletal muscles and muscles that control breathing.
Safety Considerations
The therapy carries important safety considerations, including risks of hypersensitivity reactions including anaphylaxis, infusion-associated reactions, and potential acute cardiorespiratory failure in susceptible patients. The combination therapy is contraindicated in pregnancy due to potential embryo-fetal toxicity. The most common adverse reactions occurring in 5% or more of patients include headache, diarrhea, fatigue, nausea, abdominal pain, and pyrexia.
In the United States, Pombiliti in combination with Opfolda is indicated for the treatment of adult patients with late-onset Pompe disease weighing ≥40 kg and who are not improving on their current enzyme replacement therapy.
