Paying for gene therapy. No easy terms.

An early promise of biotechnology was gene therapy- the correction of Nature’s mistakes by re-writing the genetic code to restore normal function. The complexity of the task, even for single gene defects, has proved immense and several decades on, only two gene therapies have received approval in developed economies.

Glybera®, a treatment for lipoprotein lipase deficiency developed by UniQure, received European approval in 2012 and Strimvelis®,  a treatment for severe combined immune deficiency in children (“bubble boy” disease) developed by the San Raffaele Telethon Institute for Gene Therapy (and licensed to GSK), received European approval in 2016.

In addition to being the first approved gene therapy, Glybera® has the distinction of being the most expensive drug in the world at €1.1 million. Only one patient has ever been treated and the prescribing physician had to personally call the CEO of a German health insurance provider to secure payment.  Strimvelis® is more modestly priced at just under €600,000.

As Glybera® has demonstrated, monetizing gene therapy treatments is a problem. While there are upwards of 4,000 genetic disorders, the number of treatable patients afflicted with any single disorder is minute. Only around 1 in a million individuals suffers from lipoprotein lipase deficiency, with 14 or so “bubble boy” patients in Europe.

A report from the UK’s Office of Health Economics released earlier this week covers a policy summit convened in December 2016 which brought together healthcare payers and companies developing gene therapies to discuss the challenges involved in gauging effectiveness and assigning value. Such therapies do not lend themselves to blinded clinical studies and, with such small patient numbers,  the degree of effectiveness (and cost-benefit) may not become apparent for several years after approval.

Mooted mechanisms include those used with other high cost treatments (discount and rebate arrangements, restricting eligibility or reserving as the treatment of last resort, or outcomes-based agreements, although the latter would seem to be impractical given the difficulty in assessing outcomes. However, this has not prevented GSK offering a money back guarantee on Strimvelis®. Healthcare payers could lay off some of the risk through reinsurance although amortization, where the cost of treatment is spread over time could turn out to suit payers and developers alike.

Paying for gene therapy is far from abstract. Despite a history of failure and unknown commercial return, development continues and there are now over 20 gene therapies in Phase III development. At around €1 million or $1 million a pop, healthcare systems will feel the impact even on limited gene therapy approval. One of the front runners is Spark Therapeutics, which is on the cusp of submitting a rolling Biologics License Application to the FDA for its inherited retinal disease treatment, SPK-RPE65 (voretigene neparvovec) and could win approval this year.


Gene Therapy: Understanding the Science, Assessing the Evidence, and Paying for Value. Marsden, G et al. March 2017. Office of Health Economics Research Paper. http://tinyurl.com/hn7kxko

Two very readable pieces on Strimvelis and Glybera  from Antonio Regaldo in the MIT Technology Review: 

Gene Therapy’s First Out-and-Out Cure Is Here.  Online 6th May 2016. http://tinyurl.com/gtuy25a

The World’s Most Expensive Medicine Is a Bust. Online 4th May 2016. http://tinyurl.com/zvor29x

Updated 21st April 2017:

UniQure announced that they will not renew the Glybera European marketing authorisation after its expiry in October 2017 citing "extremely limited use" as the reason.

uniQure Announces It Will Not Seek Marketing Authorization Renewal for Glybera in Europe. Company press release online 20th April 2017. http://tinyurl.com/mzppt62