European Medicines Agency rejects MAA for Amsterdam Molecular Therapeutics’ Glybera
Amsterdam – The European Medicines Agency (EMA) has rejected a market approval application for Amsterdam Molecular Therapeutics’ (AMT) gene therapy Glybera (Alipogene tiparvovec, AMT-011), the first potential cure for the inherited rare disease lipoprotein lipase deficiency (LPLD). Patients with LPLD cannot hydrolyse the triglyceride component of circulating chylomicrons and very low density lipoproteins (VLDL) and accumulate chylomicrons within the bloodstream, which can cause abdominal pain, an enlarged spleen and liver, eruptive xanthomas and potentially lethal pancreatitis. After having evaluated the results of three clinical trials on 27 LPLD patients provided by Amsterdam Molecular Therapeutics, the EMA’s CHMP said that the firm did not provide sufficient evidence of persistence in lowering blood fats in a clinically relevant manner and that there were too few patients for whom sufficiently long-term data were available. Additionally, the Committee said there was also insufficient evidence of a reduction in the rate of pancreatitis. In the current stage, the data would be not sufficient to outweigh the risks associated with injection of the non-replicating, non-integrating adeno-associated virus carrying LPLS447X, a gain of function mutation of LPL. Additionally, it would not outweigh the risks associated with immunosuppression administered to boost tolerance of the therapy. Amsterdam Molecular Therapeutics said it believes that Glybera can receive a positive opinion subject to generating additional data from existing patients. The firm asked the EMA to re-examine the clinical data package. The company announced it will initiate a study to examine further how already treated patients handle chylomicrons over time. In addition, AMT will continue to collect follow up data on pancreatitis incidence.