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Uncertainty for gene therapy following withdrawal from market of Europe’s first gene therapeutic

Dutch biotechnology company uniQure B.V., (NASDAQ:QURE), Amsterdam, The Netherlands, has announced that it will not pursue the renewal of its Glybera (alipogene tiparvovec) marketing authorization in Europe, scheduled to expire on October 25, 2017. The withdrawal by uniQure has nothing to do with safety issues according to the company, instead matters of pricing, re-imbursement and market size appear to have determined the decision. The Glybera treatment costs an average of $1 million per patient per treatment. While several other companies have gene therapies in the pipeline, many for currently untreatable ophthalmic disorders, it is hoped that a similar fate may be avoided for several promising ocular treatments.


Glybera, a gene replacement therapy for the ultra-rare disorder, lipoprotein lipase deficiency, failed to win national re-imbursement in any European country and, to date, has been used in only a single patient, re-imbursed from the German employees’ sickness fund (DAK). The principle behind many gene therapy approaches is to treat the underlying cause, and not just the symptoms, as most current medicines function. As such, a one-off treatment that permanently treats a condition is seen as highly valuable by all stakeholders. However, key questions under debate are how “valuable” is valuable, what is the upper limit in value, and what happens if the treatment doesn’t work once payment has been made? Resolution to such issues will be critical if this new class of medicines are to become a standard of care, albeit in a niche area of medical practice.


Although Glybera was the first gene therapy approved by the EMA, it may not be representative of what is coming down the tracks. The treatment did not meet its primary endpoint in clinical trials and there were question marks over the duration of its effect. Approval of the drug in CHMP was practically split at 16 to 15 votes, following a long and torturous process, and the indication itself has a number of alternate treatment options for the estimated 350-700 patients worldwide. If you compare this with a number of ocular focused gene therapy initiatives it is clear that in general, no alternative ophthalmic treatments are available for several genetic retinopathies, patient numbers worldwide are far higher than those for Glybera, and most sponsors have worked quite diligently with regulators to demonstrate safety and long-term effects before market authorisation is applied for. Nevertheless, data is still thin on the ground from a payer’s perspective. Only two gene therapies have been approved in Europe and none in the United Sates. Consequently, there is little direct knowledge on the real-world efficacy or the duration of treatment effects, key variables required in any economic model that attempts to assess value. While Glybera may in hindsight be an outlier on the economic stage, there are routes to navigating a path that may benefit both patients and payers, a route worth pursuing if the goal of treating causes rather than symptoms is to be realized.