Lysosomal Storage Disorders (LSDs) are rare metabolic diseases caused by the malfunction, or deficiency, of specific enzymes that cause disruption in the function of the lysosome, the intracellular organelle with a role in the metabolism of lipids and glycoproteins. Since the identification of the first LSD, Tay-Sachs disease, in 1881 approximately 60 LSDs have subsequently been identified.

Prospects for patients with the more severe forms of LSDs (in most cases with infantile or early juvenile onset) have typically been extremely poor, with childhood mortality extremely common. The predominant reason for their poor prognosis is a lack of treatment options. Bone marrow transplant  and hematopoietic stem cell therapy present high-risk treatment strategies without guaranteed success. Most research into pharmacological treatments to date has focused on enzyme replacement therapy (ERT) to substitute for the malfunctioning enzyme at the root of the disease. However, since the launch of the first ERT alglucerase (Genzyme's Ceredase) for the treatment of Gaucher disease type I in 1991, only nine more ERTs have launched, covering the treatment of just five more LSDs.

However, on Friday, February 14, the FDA provided approval for the ERT elosulfase alfa (BioMarin Pharmaceutical's Vimizim), as the first treatment option for patients with Morquio A Syndrome (MPS IVA). Affecting approximately 800 patients n the United States, until now patients with Morquio A had limited treatment options, often resulting in early mortality.

In addition to the increasing number of available ERTs, additional pharmacological options have become available for the treatment of LSDs. Miglustat (Actelion's Zavesca) is a substrate reduction therapy (SRT) reducing the synthesis of most glycosphingolipids that is a treatment option for patients with Gaucher disease type I and Niemann-Pick disease type C. Additionally, eliglustat (Sanofi's Cerdelga) is another SRT which has been filed for treatment of Gaucher disease in both the United States and Europe.

Migalastat (Amicus Amigal) is a Phase III drug in development for Fabry disease that also presents a novel mechanism of action, acting as a chaperone therapy to the enzyme alpha-galactosidase A, increasing the enzyme's stability and therefore increasing its likelihood of passage to the lysosome in active form where it is required.

A major factor in the increasing availability of novel therapies for the treatment of LSDs is the contribution of the FDA. One-third of the novel drugs approved by the FDA in 2013 were for rare diseases, with a significant number being first-in-class. Due to the rare nature of LSDs, the majority of therapies in development qualify for at least one of the FDA's expedited approval pathways. Of the 34 drugs designated as a breakthrough therapy in 2013, approximately one-third were for genetic diseases, significantly increasing the speed with which these drugs can reach the market.

While the occurrence of LSDs remains rare, for those patients afflicted with an LSD, the impact on their quality, and indeed duration, of life remains severe. However, these developments hint at better times ahead for these patients.

Decision Resources will release a Pharmacor report covering LSDs later in 2014. For more information on this report, please contact us at

Eamonn O'Connor is a business insights analyst with the Cardiovascular, Metabolic and Renal Disorders team at Decision Resources Group.

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