First therapy to treat two types of Niemann-Pick disease, a rare genetic metabolic disorder

News 20/05/2022

EMA has recommended granting a marketing authorisation in the European Union (EU) for Xenpozyme (olipudase alfa), a therapy for the treatment of non-central nervous system (CNS) manifestations of Acid Sphingomyelinase Deficiency (ASMD), a rare and progressive genetic disease. Xenpozyme is indicated for use in children and adults of all ages with type A/B or type B ASMD.

Historically referred to as Niemann-Pick disease types A (NPD A) and B (NPD B), ASMD is a genetic disorder. It belongs to the larger family of metabolic disorders called 'lysosomal storage diseases', in which fats build up within the parts of the body's cells that break down nutrients and other materials. This affects the way cells work and causes them to die, affecting normal functioning of tissues and organs. ASMD is seriously debilitating and life threatening since the build-up of fatty substances can cause brain damage and swelling of organs such as liver and spleen.

There are currently no approved medicines in the EU that modify the disease or slow the rate of its progression. Patients receive only palliative and supportive care to manage the symptoms. As a result, morbidity and mortality are high, especially in children. The most common causes of death are respiratory disease, liver problems and complications due to the excessive size of multiple organs. Children with type A ASMD usually die before their third birthday. The median life expectancy for type B patients is 17 years.

Xenpozyme is the first ASMD-specific treatment. This medicine is an enzyme replacement therapy, developed to replace patients’ deficient or defective enzyme, acid sphingomyelinase (ASM), and thereby reduce fat accumulation within cells and relieve some of the symptoms of the disease. The highest potential for clinical benefit is expected in patients with chronic visceral forms of ASMD (type B). The replacement enzyme is produced by a method known as 'recombinant DNA technology': it is made by cells into which a gene (DNA) has been introduced, that enables them to produce the enzyme. Xenpozyme is available as powder for solution for infusion, administered intravenously every two weeks.

EMA’s human medicines committee (CHMP) based its recommendation for marketing authorisation on positive results from three clinical trials in patients with ASMD. The first one was a randomised placebo-controlled pivotal trial in 36 adult patients with ASMD type B and type A/B. The second was a single-arm study in 20 patients (4 adolescents, 9 children, 7 infants/young children) designed to support the paediatric indication, with a main focus on safety, pharmacokinetics and efficacy. Both trials demonstrated an improvement in lung function and reduction of spleen and liver volumes, suggesting relevant clinical benefit. An additional long-term follow-up study is ongoing to address the safety and persistence of efficacy over a longer treatment duration. Overall, 67 ASMD patients (47 adults, 20 paediatric patients) were included in the clinical program.

The adverse events of Xenpozyme were generally mild to moderate and, in most cases, manageable. The majority were related to infections, infusion-related reactions, or gastro-intestinal complaints (disease signs and symptoms in children).

Xenpozyme was supported through EMA's PRIority MEdicines (PRIME) scheme, which provides early and enhanced scientific and regulatory support to medicines that have a particular potential to address patients' unmet medical needs. EMA’s CHMP reviewed the application for Xenpozyme under its accelerated assessment procedure, which allows the speeding up of patients' access to medicines.

The opinion adopted by the CHMP is an intermediary step on Xenpozyme’s path to patient access. The opinion will now be sent to the European Commission for the adoption of a decision on an EU-wide marketing authorisation. Once a marketing authorisation has been granted, decisions about price and reimbursement will take place at the level of each Member State, taking into account the potential role or use of this medicine in the context of the national health system of that country.

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