Cystinosis is an autosomal recessive disease caused by a mutation in CTNS, which encodes the lysosomal transporter of cystine. This leads to intracellular cystine accumulation which leads to renal, neurological and cardiac damage. The treatment for this condition is life-long cysteamine. Back in 2011, we reported on a new formulation of cysteamine that is given just twice daily (rather than q6 hours) and is associated with a lower incidence of side effects including halitosis and body odor. There was a higher incidence of GI side effects in patients treated with the new drug. The halitosis occurs because a proportion of the drug is converted to dimethylsulfide and this can appear in expired air. The reason why the new formulation is associated with less halitosis is because, although serum drug levels are the same as with the older drug, the total dose is reduced so there is less overall conversion to the offending metabolites. This is welcome news for patients given that the drug should be started before age 5 and the halitosis and body odor cause major social problems for patients which can result in non-compliance.
Yesterday, the FDA approved cysteamine bitartrate ER (Procysbi) for the treatment of cystinosis. Essentially, this is an enteric-coated delayed-release version of the drug that is largely absorbed in the small intestine. The major issue, of course, is cost. The traditional form of the drug costs about $8,000/year while the new formulation will cost approximately $250,000. That is an enormous difference for a drug which does no more than reduce side effects. However, when you read this New York Times article on procysbi, you can better understand why the parents of these children think that this is entirely worth it.
According to the same article, it is estimated that by 2018, spending on orphan drugs will account for about 16% of overall spending on prescription drugs. This is bound to lead to conflict between insurers, patients and the manufacturers when trying to decide who to treat and who will pay. Is it worth $242,000 every year for a drug to be given twice, rather than four times daily? The problem, of course, is that this is the only way that the company can recoup the cost of development because there are so few patients with the disease - approximately 300 in the US. It should be remembered, of course, that the ulitmate cost of non-compliance in this case is very high - dialysis, transplantation and loss of future earnings so the cost calculation is not as simple as I suggested above. This is a debate that is certainly going to continue over the next few years.