For the second time, the company that owns Glybera, the only gene therapy approved in the West, has achieved a public listing. Netherlands-based UniQure got away on the Nasdaq exchange in February, marking the end of a period in which it was taken private to keep its gene therapy portfolio active.
A European launch is slated for mid-year by its partner Chiesi, and with its accounts topped up by $92m from its initial public offering UniQure believes it is funded through the launch as well as early-stage data readouts of gene therapy trials in haemophilia B, porphyria, Sanfilippo syndrome type B and Parkinson’s disease in 2014 and 2015. But it was the 2012 approval of Glybera that helped validate everything that UniQure is trying to do today, says its chief executive, Jörn Aldag.
“It has moved the industry significantly in the sense that people gained confidence that gene therapy will be a medicine for the future,” Mr Aldag tells EP Vantage.
Treating at the source
Glybera is approved in the ultra-rare condition familial lipoprotein lipase (LPL) deficiency, which prevents the body from breaking down fat from digested food. This has a prevalence of as few as one in a million patients. Pancreatitis, high triglyceride levels and enlarged livers are among the symptoms; treatment protocols have previously attempted to limit dietary fat to 20 grams a day.
The therapy delivers the LPL gene to cells, with a particular affinity toward muscle cells, and as a naturally occurring variant that produces the enzyme at higher levels. Glybera is administered as a one-time series of up to 60 intramuscular injections in the leg while patients are under sedation or anaesthetised.
As a gene therapy treating an incredibly uncommon condition, Glybera faced an unusual approval pathway – the pivotal trial that supported its eventual approval had only 27 patients, and it was reviewed by two European Union regulatory panels, the Committees for Advanced Therapies and the Committee for Medicinal Products for Human Use (CHMP).
The EU panels relented after initial rejection, but not before the publicly traded predecessor company Amsterdam Molecular Therapeutics had to be dissolved. A group of the company's backers, led by the venture capital firm Forbion, picked up AMT’s holdings under the newly created private group UniQure (Glybera gets happy surprise in form of European backing, July 20, 2012).
It is notable that Glybera has only managed to reach approval in the EU, but its developer has floated in the US on Nasdaq, a contradiction that speaks to the relative strengths of the regulatory regime and investment community in each region.
“The company is now up and listed on the Nasdaq, which we believe to be the major stock market in the world for biotech companies with the largest number of peers,” Mr Aldag says.
Rollout and planning
The partnership with the private Italian company Chiesi signed last year brought in €17m ($23.6m) up front and an equity investment of €14m for rights to Glybera in Europe and some countries in Asia and the Americas. Pricing has not been established as Chiesi is negotiating with national authorities – Germany is an initial focus – but it will no doubt have an effect on uptake, especially as a small-molecule competitor in the form of Novartis's LCQ908 is nearing the conclusion of phase III.
UniQure retains US rights, and believes a phase IV trial in 12 patients as part of its European post-marketing commitments, in addition to the data developed so far, should be sufficient to support a US BLA. UniQure should be able to file in 2017, Mr Aldag says.
In preparation for a potential rollout in the US, UniQure is building production capacity in the US near Boston that will allow it to manufacture commercial-grade adeno-associated virus (AAV) products, the vector on which its gene therapies are delivered. Mr Aldag describes it as the world’s largest such facility.
In the meantime, the group should have several more opportunities to let that AAV platform shine. The haemophilia B programme, which Chiesi has licensed in all of the Glybera territories except China, will begin a phase I/II dose-escalation trial in 2014 and should deliver results in the second half of 2015. If this is successful, a pivotal trial would follow immediately and a regulatory filing could come in 2017, Mr Aldag says.
As with Glybera, the aim is for a one-off treatment that would allow haemophiliacs to begin producing factor IX on their own, which would avert the need for repeated prophylactic infusion of factor IX. The most advanced products in haemophilia B require dosing at least once every 10 days.
The porphyria project should report phase I data later in 2014, while the Sanfilippo B syndrome therapy will report phase I/II data in 2015.
Mr Aldag said the IPO funding would support the company through the second half of 2015, by which time the clinical programmes will have read out. All are being developed with outside collaborators.
Even if disappointment has been the rule in gene therapy Mr Aldag believes the future is bright because of the evolution of diagnostic technologies to support the technology, which should encourage more companies to come into the field (Therapeutic focus – Gene therapy slowly rises from the ashes, February 26, 2014).
“If you understand what is genetically wrong with a certain disease you can treat at the source,” he says. “The overall environment will fuel a rapid and significant development of gene therapy.”