The rising cost of orphan drugs
Authors: None The Lancet Haematology
Journal: The Lancet Haematology (2015)

Eculizumab is a humanised recombinant monoclonal IgG2/4 antibody that selectively targets and inhibits the terminal portion of the complement cascade. It is also one of the most expensive drugs in the world, topping a list published by Forbes in 2010; costing an estimated £3150 per 30 mL vial, with a year's worth of treatment costing close to £350 000 (exact costs are proprietary information by the manufacturer). The drug, marketed as Soliris by Alexion Pharmaceuticals, is used for the treatment of the rare diseases paroxysmal nocturnal haemoglobinuria (PNH) and atypical haemolytic uraemic syndrome (aHUS). PNH affects one or two individuals per million, and numbers are similarly low for aHUS, although the exact incidence has been difficult to determine. The drug is not a cure for either orphan disease, but can improve quality of life. Eculizumab was designated an orphan drug in 2011 when the US Food and Drug Administration approved it for aHUS. Earlier this year, eculizumab for the treatment of aHUS became the first drug to be considered, and approved, in the UK under the National Institute for Health and Care Excellence (NICE) highly specialised technologies programme which aims to evaluate treatments for very rare conditions. Although actual costs remain confidential, NICE estimates that this drug will cost the NHS up to £58 million in the first year, rising to £82 million after 5 years, based on information available in the public domain. Eculizumab is the only drug Alexion currently produces, but has resulted in net product sales of more than US$6 billion since 2010. Some countries are now questioning the cost of the drug. Canada's Patented Medicine Prices Review Board is challenging the cost, saying the price could be considered excessive and that it costs more in Canada than anywhere else in the world. The Board has held a series of pre-hearing conferences with plans for a public hearing into the matter. Alexion has responded by filing a motion with the Canadian Federal Court on Sept 11, asking for the review board to be prohibited from going ahead with its hearing—or from making any order that would affect the price of eculizumab. The ongoing dispute over the cost of eculizumab is yet another example of recent price increases for drugs for a whole range of health conditions. The recent price rise of pyrimethamine (marketed in the USA as Daraprim), the only drug currently approved for the treatment of toxoplasmosis in immune-compromised individuals in the USA, caused much public outcry. When Turing Pharmaceuticals acquired the US production rights to pyrimethamine, the price rose from $13·50 per pill to a reported $750 per pill. The company had announced that it would back down from this price point but it is likely that the final cost will be higher than what it was originally, and the cost of the drug was still high a few weeks after the announcement. These sorts of pricing decisions are not restricted to rare diseases and single drug companies. On Feb 10, Valeant Pharmaceuticals International Inc bought the rights to a pair of life-saving heart drugs, sodium nitroprusside and isoprenaline, and subsequently raised their list price substantially. This resulted in all 18 Democratic Members of the US House Committee on Oversight and Government Reform to request a subpoena for documents related to the price increases for the two drugs. So what is driving the price increases for these drugs? It's unlikely that cost of manufacture of these medicines is drastically increasing, and there are no indications that the formulation of the drugs has been improved from laboratory research and tested in clinical trials. Is it simply a matter of what the market will bear? Often pharmaceutical companies cite research and development costs as justification for high drug costs, but this reasoning does not stack up with these examples. It can often feel that pharmaceutical companies are more concerned about marketing and asset acquisition than being true drug and health product producers with a strong backbone of research and development. As much scientific and medical research is funded and conducted by public institutions and charitable monies, is it in the patient's and health-care providers best interest to have a company enter the arena at the final stage and then reap substantial benefits? An alternative is needed, perhaps in the form of not-for-profit research and development agencies, which have the business know-how to translate scientific discoveries into useful medicines, which could re-invest revenue into more research. Although the way the free market is currently operating can be difficult to reconcile with what is affordable for health-care providers, it is encouraging to note that an alternative to Daraprim was announced on Oct 22, at the modest price tag of $1 per pill, and a biosimilar is in development for eculizumab.