• People in Europe with a rare, inherited blood disorder now have a shot at a one-time fix for their disease as the European Commission granted conditional approval to a gene therapy developed by Cambridge, Massachusetts-based Bluebird bio.
• Zynteglo, as Bluebird’s treatment will be sold, is approved for a type of transfusion-dependent beta-thalassemia, a genetic disease that results in reduced or missing hemoglobin. Without sufficient numbers of the crucial oxygen-carrying protein, patients require chronic blood transfusions for life.
• To produce its gene therapy, Bluebird uses an inactivated virus to insert a functional copy of a modified beta-globin gene into stem cells extracted from a patient’s body. In clinical testing, most patients infused with the therapy were able to stop receiving transfusions, with follow-up for some stretching out two to four years.

Zynteglo is Bluebird’s first drug to be approved and is the first gene therapy to be cleared for use in transfusion-dependent beta-thalassemia.

Its marketing authorization from the European Commission follows landmark approvals from the Food and Drug Administration for Novartis’ Zolgensma and Spark Therapeutics’ Luxturna, which respectively treat spinal muscular atrophy and a type of inherited eye disease.

Taken together, the therapies illustrate the rapid advances made in gene therapy over the past several years, as more and more diseases appear treatable by correcting dysfunctional genes. Commercializing such therapies is another question, though, given high costs of treatment and complex production.

The conditions all three drugs treat are rare, with only a few hundred to a few thousand patients diagnosed each year. In Bluebird’s case, estimates put the number of people in the EU who could initially receive Zynteglo at between 2,000 and 3,000.

The European Commission cleared Zynteglo for a specific genotype of transfusion-dependent beta-thalassemia, and for those patients aged 12 and older who are able to receive a stem cell transplant but have no matched donor.

Data supporting the approval come from two completed trials and two ongoing studies. In 11 of the 14 patients treated in the earlier clinical tests, Zynteglo spurred sufficient production of gene-therapy-derived hemoglobin to permit halting of blood transfusions.

That independence has now been maintained in all 11 through 21 to 56 months.

Such a benefit could also help avoid the iron buildup that commonly occurs in beta-thalassemia patients as a result of transfusions. Over time, excessive iron can lead to progressive multi-organ damage.

As with other gene therapies, one of the biggest questions about commercial use of Zynteglo is what it will cost and how it will be reimbursed. Bluebird has said the drug offers a “lifetime intrinsic value” of more than $2 million, and hopes to spread payments over five years.

No price was announced Monday, however. “We plan to provide an update on our plans, including price by the end of next week,” a company spokesperson wrote in response to BioPharma Dive.

Zolgensma’s price of $2.1 million per patient made it the most expensive drug ever brought to market. Luxturna, which is injected in each eye, costs $425,000 per eye.

Wall Street analysts don’t expect Zynteglo to become a big seller based on its approval in Europe. But the experience Bluebird gains in launching the therapy could prove critical for its pipeline of gene therapies for sickle cell disease, multiple myeloma and a metabolic disorder known as adrenoleukodystrophy.

Bluebird hopes to launch Zynteglo in the U.S. next year. In the EU, the company will roll out the therapy first in Germany, followed by Italy, the U.K. and France.