A quick scan of ultra-rare metabolic diseases revealed that for some products are on the market, such as tyrosinemia type I (Nitisinone; Orfadin®) and N -acetylglutamate synthetase (NAGS) deficiency (Carglumic acid; Carbaglu®). For others, products are in development. Apparently, given the right circumstances orphan drug development for ultra-rare metabolic disorders is feasible.
Currently, I am performing a comparative study between exceptionally rare metabolic disorders (prevalence 50-5000 patients or 0,01-1/100,000 inhabitants) with at least one orphan drug (OD) in development and exceptionally rare disorders with no OD in development. The dataset consists of 168 ultra-rare metabolic diseases: 36 with at least 1 OD and 132 with no OD. Only diseases that have a genetic component are included.
The aim of the study is to identify factors that provide an explanation for the difference between the two groups of rare metabolic diseases.
For example the aforementioned quick scan already hinted to the important role of patients (or parents of) in rare disease research and orphan drug development (See Role of patient for some admirable examples). Other factors that may be relevant are a.o. availability of an animal model, registry for natural history, diagnostics, biochemical elucidation, role of genetics, sharing molecular pathway or target with other (rare) disorders with approved therapy. An example of the latter is the aforementioned Nitisinone that is currently being tested in the clinic for alkaptonuria, an ultra-rare metabolic disorder.
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