Mathias Schmidt, PhD, President and CEO of JCR Pharmaceuticals USA, discusses long-term efficacy and safety data of pabinafusp-alfa (Izcargo) in mucopolysaccharidosis type II (MPS II; Hunter syndrome). Data from this study was recently presented at WORLDSymposium 2022.
MPS II is a rare, progressive lysosomal disease caused by deficient activity of iduronate-2-sulfatase, attributable to pathogenic variants of the iduronate-2-sulfatase gene (IDS). This disease has a variable clinical presentation but common signs and symptoms include: developmental decline between 18 and 36 months, followed by progressive loss of skills; coarse facial features; skeletal irregularities; obstructive airway and respiratory complications; joint stiffness; retinal degeneration; and communicating hydrocephalus. Current standard of care is weekly intravenous infusions of idursulfase.
Pabinafusp alfa is an iduronate-2-sulfatase fused with anti-human transferrin receptor antibody, designed to cross the blood-brain-barrier to address neurodegeneration in MPS II. Previous clinical trials have provided positive results suggesting pabinafusp alfa is efficacious against both somatic and neurological symptoms. This data led to the approval of this drug in Japan. In the United States, the only approved treatment for MPS II is idursulfase, an enzyme replacement therapy that does not cross the blood brain barrier.
In the phase 2 portion of a phase 2/3 study, pabinafusp alfa was intravenously administered weekly to 28 patients. Heparan sulfate concentrations in the cerebrospinal fluid markedly decreased and then remained low until 104-week in all subjects. Neurocognitive tests showed a long-term stabilization or improvement in most patients. A neurocognitive improvement was also observed in some attenuated adult subjects. Liver and spleen volumes decreased significantly in the patients naïve to enzyme replacement therapy (idursulfase) and were maintained in most patients who switched from idursulfase to pabinafusp alfa. The efficacy of pabinafusp alfa against other somatic symptoms was comparable to that of conventional idursulfase. Drug-related adverse events were mild or moderate, transient, and manageable, including infusion reactions.
As Dr. Schmidt says, the phase 3 portion of the study is open for recruitment.
To learn more about MPS II and other rare lysosomal storage disorders, visit https://checkrare.com/diseases/lysosomal-storage-disorders/
