Expensive drugs for rare disorders: to treat or not to treat? The case of enzyme replacement therapy for mucopolysaccharidosis VI

Curr Med Res Opin. 2009 May;25(5):1285-93. doi: 10.1185/03007990902892633.


Background: Mucopolysaccharidosis VI (MPS VI) is a very rare, chronically debilitating lysosomal storage disorder that develops in people with an enzyme deficiency. Clinical characteristics and progression rates vary widely between patients. The recent introduction of enzyme replacement therapy (ERT) has improved considerably the lives of patients with MPS VI, at an annual cost of treatment between euro 150,000 and euro 450,000 per patient.

Scope: This Commentary article addresses the controversial topic of granting reimbursement for expensive treatment options for orphan diseases, such as MPS VI. The discussion reflects clinical, economic and ethical aspects and incorporates insights from the relevant literature (based on a Medline search to September 2008) on MPS VI, efficacy of ERT, orphan drugs, and the economics and ethics of health-care prioritisation.

Findings: Although ERT for MPS VI received marketing authorisation in the European Union in January 2006, patients' access to this therapy varies geographically due to differences between national reimbursement schemes for orphan drugs. Some inclusion and exclusion criteria for treatment of MPS VI patients with ERT appear arbitrary and may contribute to the exclusion from treatment of patients who could benefit in the long term. Reimbursement schemes which rely on proof of short-term treatment effectiveness may discriminate against slowly progressive patients, as health gain can often not be confirmed over a short period of time in these patients. Conventional cost-effectiveness analysis remains silent on crucial issues related to budgetary impact, i.e. opportunity cost from a system perspective, and fair access to treatment.

Conclusions: To prevent patients from being deprived of effective treatment, it is suggested that inclusion and exclusion criteria for treatment should be primarily based on a careful individual assessment of expected long-term clinical benefits. Once treatment has been agreed to as the correct option on clinical grounds, it is further argued that the conventional cost-effectiveness criterion currently in widespread use does not offer a sufficient basis for rejecting reimbursement of expensive treatments for exceptionally rare disorders, providing that decisions on reimbursement are intended to reflect public preferences.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cost-Benefit Analysis
  • Drug Costs* / legislation & jurisprudence
  • Guidelines as Topic
  • Humans
  • Insurance, Health, Reimbursement / economics
  • Insurance, Health, Reimbursement / legislation & jurisprudence
  • Lysosomal Storage Diseases / diagnosis
  • Lysosomal Storage Diseases / drug therapy
  • Lysosomal Storage Diseases / economics
  • Mucopolysaccharidosis VI / diagnosis
  • Mucopolysaccharidosis VI / drug therapy
  • Mucopolysaccharidosis VI / economics*
  • N-Acetylgalactosamine-4-Sulfatase / economics*
  • N-Acetylgalactosamine-4-Sulfatase / therapeutic use
  • Orphan Drug Production / economics
  • Orphan Drug Production / legislation & jurisprudence
  • Rare Diseases / drug therapy*
  • Rare Diseases / economics*
  • Treatment Outcome


  • N-Acetylgalactosamine-4-Sulfatase