By Nuala Moran
LONDON – Glybera formally became the first gene therapy to be approved in a regulated market, as the European Commission gave the rubber stamp to the treatment for the ultra-rare inherited disorder lipoprotein lipase deficiency (LPL) on Friday.
"The world has been watching very skeptically, questioning if a gene therapy could ever be approved at all," said Jörn Aldag, CEO of uniQure BV, Glybera's developer. "We are now at the beginning of a significant growth path for the gene therapy market," he told BioWorld Today.
The first patient to receive the commercial product will be treated in Germany around the middle of 2013. While awaiting approval, uniQure has screened 319 patients and found 32 with the relevant mutation in the LPL gene. "We are now correlating genotype to phenotype because we can only treat patients with acute, recurring pancreatitis," Aldag said.
It has taken a mountain of investment to reach this point, but Aldag said Glybera (alipogene tiparvovec) will be a profitable product going forward. However, Amsterdam, the Netherlands-based uniQure is facing a short-term funding gap between now and when the revenues start to come in, and it is looking to raise €20 million (US$26.7 million) over the next five months.
"This won't be a problem," Aldag said. "Show me a biotech that has ever brought a drug to market; there aren't so many. With this regulatory approval, we have the potential for similar commercial development as with monoclonal antibodies."
Investors will not only be buying into Glybera, but also into four other gene therapy products that have approval to enter clinical trials in the next nine months. Those are: a treatment for hemophilia B in which the gene for the blood-clotting protein Factor IX will be delivered into patients' liver cells; a therapy for acute intermittent porphyria, in which uniQure will use its adeno-associated viral vector to deliver correct copies of the gene coding for porphobilinogen-deaminase, an enzyme involved in the production of heme; a treatment for Parkinson's disease in which it is planned to administer the gene for glial cell line-derived neurotrophic factor, a protein that stimulates production of dopamine and prevents further deterioration of dopaminergic neurons; and a gene therapy for the rare liposomal storage disorder Sanfilippo B, in which it is planned to deliver the gene for alpha-N-acetylglucosaminidase to arrest the progress of that inherited condition, which causes profound mental retardation and early death.
Of course, uniQure's level of profit hangs on what reimbursement bodies are to offer for Glybera as a one-off treatment with a profound and long-term impact. Aldag said the company is working with payers to set prices, with different countries preferring different schemes.
The target is to get a similar price tag to enzyme replacement therapies for treating lysosomal storage disorders, which currently are around €250,000 per annum. There could either be an annual price for Glybera, with patients being invited for a medical assessment before the fee is paid, or a single up-front charge. Aldag said some reimbursement bodies favor that approach, where it would be a case of multiplying the annual cost of treating a similar disease by the number of years Glybera is known to have an effect. Currently that is five years.
In total, uniQure estimated there are 400 to 500 patients in Europe eligible to receive Glybera. They will be assessed and the product for treating each of them individually manufactured at uniQure's Amsterdam facility.
Aldag expects there will be three clinical centers in Germany administering the product, with others in Turkey, the UK, France, Italy and elsewhere in Europe.
Now that it has European Medicines Agency approval for Glybera, uniQure intends to engage with the FDA, with the aim of a U.S. launch in 2014.
"I don't know at this point if the FDA will need any more data. As this is an ultra-rare orphan disease, I hope they won't request further trials. Most of the patients [in the submitted studies] were dosed in North America, in Canada," Aldag said.