On 2 November 2012, uniQure announced that the European Commission has granted the company the "go ahead" for the commercialisation of its product Glybera (alipogene tiparvovec) in the European Union - making Glybera the first gene therapy approved for human use by regulatory authorities outside of China and the Philippines. 

uniQure develops human gene based therapies using adeno-associated viral (AAV) derived vectors as the delivery vehicle of choice for therapeutic genes and has applied them to a large number of ultra-rare (orphan) diseases each caused by one faulty gene.  One of those human gene based therapies is Glybera, a therapy for patients with the genetic orphan disorder lipoprotein lipase deficiency (LPLD, also called familial hyperchylomicronemia), consisting of multiple intramuscular injections resulting in the delivery of functional genes to the patient’s muscle cells.  LPLD is an extremely serious, painful and potentially lethal condition that leads to acute and recurrent pancreatitis attacks causing in many patients early onset diabetes and cardiovascular complications, and to which no treatment existed until last week.

While Glybera’s approval will have a dramatic impact on the lives of these patients, there are concerns over the technology’s efficacy (given the inherent limitations of the evidence base for an orphan disease) and the authorisation comes with certain conditions.  It needs to be prescribed and administered under the supervision of a physician with expertise in treating patients with LPLD and in gene therapy administration, as well as in full consultation with the patient.  Detailed recommendations for its use will be described in the European public assessment report (EPAR) and available in all official European Union languages.

In addition to the ultra-rarity of the patient subset to consider, one question to consider is how governments and health insurers across Europe will treat Glybera, especially given that the therapy is expected to be priced at over €1.25 million per patient.  uniQure’s chief executive suggested an innovative financing model for Glybera using an "annuity stream", so that hospitals would be charged a proportion of the total price each year over certain amount of years. 

Even if Glybera’s path through the regulatory authorities has been anything but smooth sailing, it denotes a major step forward in making gene therapies available for a large number of orphan diseases that have a remarkable unmet medical need.  There is no doubt that, with the regulatory authorities being strict and watchful and after all the trials and tribulations experienced by the gene therapy field over the years, the approval of Glybera represents a key milestone.  The European authorities still continue looking into the regulatory framework for advanced therapies, which currently needs alignment for orphan drugs.  Following the experience with Glybera, it will be interesting to see whether in the future (a) the European Commission streamlines its processes for the approvals of gene therapies and treatments for orphan diseases in general; and (b) the Committee for Medicinal Products for Human Use (CHMP) will be more ready to recommend other such therapies under the ‘exceptional circumstances’ approach (under Article 14(8) of Regulation (EC) No 726/2004 and in line with the new European pharmacovigilance framework). 

uniQure plans to roll-out Glybera’s commercialisation in Europe in the summer of 2013. The company has already announced its plans to apply for regulatory approval of Glybera in the US, Canada and other markets next year – we remain curious to see whether such markets will follow the European example.