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FDA Grants ‘Breakthrough Therapy’ Designation to Olipudase Alfa

Enzyme-replacement therapy treats Niemann–Pick disease type B

The FDA has granted “breakthrough therapy” status to the enzyme-replacement therapy olipudase alfa (Genzyme/Sanofi), which is being investigated for the treatment of patients with non-neurological manifestations of acid sphingomyelinase deficiency (ASMD) –– also known as Niemann-Pick disease type B, as opposed to type A, which is characterized by neurological involvement.

ASMD is a serious, life-threatening disorder caused by insufficient activity of the ASM enzyme, which results in toxic accumulation of sphingomyelin. No approved treatment options are currently available for patients with Niemann–Pick disease type B.

A “breakthrough therapy” designation is intended to expedite the development and review of investigational new drugs that target serious or life-threatening conditions. The designation is granted when an investigational treatment has shown preliminary clinical evidence of substantial improvement on a clinically significant endpoint compared with available therapies.

Olipudase alfa is being developed to address the fundamental defect underlying ASMD. Supplementing the defective or deficient native enzyme with olipudase alfa allows the breakdown of sphingomyelin, whose accumulation is responsible for the clinical manifestations of ASMD.

The “breakthrough therapy” designation was supported by data from a phase Ib study of olipudase alfa. Findings in five adult patients with non-neuropathic ASMD were presented at the Lysosomal Disease Network’s WORLD Symposium in February 2015. The data presented on the repeat-dose safety, pharmacodynamics, and exploratory efficacy of olipudase alfa supported its continued development for investigational use in non-neurological manifestations of ASMD.

Genzyme has started enrollment in a phase I/II pediatric study and is preparing for enrollment in a phase II/III study in adults in the second half of 2015.

ASMD is one of a group of lysosomal storage diseases that affect metabolism and that are caused by genetic mutations. ASMD is caused by deficiency of the ASM enzyme, which is found in special compartments within lysosomes and is required for the metabolism of the enzyme sphingomyelin. If ASM is absent or is not functioning properly, sphingomyelin cannot be metabolized properly and is accumulated within lysosomes, eventually causing cell death and the malfunction of major organ systems. Niemann–Pick types A and B are both caused by the same enzymatic deficiency, and there is growing evidence that the two forms represent opposite ends of a continuum.

Source: Genzyme; June 4 2015.

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