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UniQure to Yank Pioneering Gene Therapy From Market in Europe

Xconomy Boston — 

[Updated, 9:33 a.m. ET, see below] It took decades to get the first gene therapy in the Western world to market. And it will apparently take only five years since for that product, a treatment from UniQure for a rare metabolic disorder, to fizzle out after failing commercially.

UniQure (NASDAQ: QURE), with operations in Amsterdam and Lexington, MA, said this morning that it will not seek to renew marketing authorization of alipogene tiparvovec (Glybera), the Western world’s first approved gene therapy, in Europe. A five-year conditional approval of the therapy is set to expire on Oct. 25, after which time UniQure will pull the drug from the market and wind down all the related infrastructure. The product will still only be available for patients who were approved for treatment and reimbursement before Oct. 25, though that will be handled by UniQure partner Chiesi.

The decision was made after a “careful and thoughtful evaluation of patient needs and clinical use of the therapy,” said CEO Matthew Kapusta in a statement. “Glybera’s usage has been extremely limited and we do not envision patient demand increasing materially in the years ahead.”

UniQure expects to cut expenses by about $2 million per year after pulling the drug.

The decision ends a strange odyssey for UniQure, which was formed as Amsterdam Molecular Therapies in 1998 and has played an important, albeit now somewhat dubious role in the field of gene therapy. The company started out developing therapies for an ultra-rare genetic disease, familial lipoprotein lipase deficiency, and latched onto gene therapy—a method of providing a one-time, long-lasting, if not permanent treatment for a genetic disease—as its method to do it.

UniQure went through a series of ups and downs pushing alipogene tiparvovec through clinical testing and trying to get it approved in Europe—the product was rejected by regulators three times. And in the meantime, the field of gene therapy was going through its own roller coaster ride, trying to overcome past safety and other problems to prove its worth as a viable therapeutic option. Investments in gene therapy had all but dried up in the early 2000s due to such problems, but technological advances were made that improved the engineered viruses, or “vectors” that help deliver the treatment. Promising data began to emerge, and the field got a further jolt when in the midst of all of it, alipogene tiparvovec was finally approved in Europe in 2012.

Gene therapy has since pushed forward more rapidly. Another gene therapy, from GlaxoSmithKline for a rare immune deficiency, was approved in 2016. Gene therapy startups began attracting investments again, and many developers, like Spark Therapeutics (NASDAQ: ONCE), BioMarin Pharmaceutical (NASDAQ: BMRN), and Bluebird Bio (NASDAQ: BLUE), have amassed clinical data in humans suggesting the method could be useful in multiple diseases, like hemophilia, beta thalassemia, and sickle cell disease. A product from Spark for a genetic form of blindness could soon be the first ever approved in the U.S.

[Updated with info from UniQure spokesman] Yet UniQure’s therapy—the second ever approved gene therapy, next to a cancer treatment approved in China in 2003—was a commercial failure, as this profile from MIT Technology Review detailed last year. The drug was famously initially priced at around $1 million in Europe, but just didn’t have a large commercial market to make it worth continuing to sell. According to UniQure spokesman Tom Malone, just one patient has received Glybera since it was approved for reimbursement in 2014. That patient was treated at the Charité University Clinic in Berlin, Germany, in 2015.

In the meantime, UniQure had to build a global registry to track patients long-term, run a post-approval trial, file for annual regulatory reassessments, and more. Those activities, UniQure said in a statement today, required “significant infrastructure” and the company had to pay for all of it. Additionally, UniQure decided not to pursue approval in the U.S., because it would’ve had to run another trial, which didn’t make sense economically.

Add it all up and the program was more of a burden than a benefit to UniQure, one of the reasons in late 2016 the company restructured around programs for hemophilia B, Huntington’s disease, and heart disease. As Sander Van Deventer, a managing partner at Forbion Capital Partners and co-founder of UniQure, told Xconomy in 2016: “If you want to do something like a gene therapy and you want to make sure that there’s a paradigm shift in how you treat patients, it’s never easy—but I think one of the things I would have probably done differently is choose a different disease.”

Yet despite its failure commercially, the drug’s impact lasts, at minimum, as proof that gene therapy developers can make it to the finish line. Said Van Deventer in 2016, many of the gene therapy companies “I’m pretty sure wouldn’t have been there if there were not Glybera.”