EMA Recommends Treatment for Maple Syrup Urine Disease

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has granted an exceptional circumstances positive opinion for Maapliv, a solution of amino acids intended for the treatment of maple syrup urine disease (MSUD) in patients presenting with an acute decompensation episode from birth and who are not eligible for an oral and enteral branched-chain amino acids (BCAA)-free formulation.

MSUD is a rare genetic disorder of BCAA metabolism. In this condition, buildup of toxic metabolites from BCAAs produced from protein breakdown leads to significant and potentially irreversible developmental effects. It may cause metabolic derangements, cerebral edema, seizures, coma, and respiratory failure, and it may be fatal. It affects fewer than 0.1 in 10,000 people in the EU, equivalent to fewer than 5000 people.

This is below the ceiling for orphan drug designation (5 in 10,000). In 2020, the EMA granted orphan designation to a solution of amino acids not containing any BCAAs, intended to be given by infusion to replace other sources of amino acids. At the time, the EMA said, there were no suitable treatments authorized in the EU for MSUD, and patients were managed with strict diets to control the amount of BCAAs taken in from proteins. Some forms of the disorder also responded to vitamin B supplements. Some patients needed hospitalization for enteral feeding or procedures to filter BCAAs directly from the blood. Other patients were judged suitable for liver transplantation, which restores the ability to break down BCAAs.

Medicine Reduces Harmful Amino Acids

Maapliv, manufactured by Recordati Rare Diseases, is a combination of amino acids free of BCAA. It is used as a solution for infusion in combination with carbohydrate and lipid supplementation to prevent or reverse protein catabolism and promote anabolism in patients with MSUD decompensation, thereby reducing harmful alpha-keto acid levels.

The CHMP said that leucine normalization had been shown in patients with MSUD decompensation who are given Maapliv in five scientific publications that reported on parenteral use of BCAA-free solutions with the same formulation as Maapliv. Treatment with Maapliv should be initiated under the supervision of a physician experienced in the management of MSUD disease.

Detailed recommendations for the use of Maapliv will be described in the summary of product characteristics, which will be published on the EMA website in all official European Union languages after the marketing authorization has been granted by the European Commission.