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Dive Brief:

• Bluebird bio, the Cambridge, Massachusetts-based drug developer, said Tuesday that its beti-cel gene therapy has been officially submitted for approval in the U.S., marking the latest step in what's become a protracted journey for the therapy.
• Beti-cel was tested in multiple early- and late-stage clinical trials as a one-time treatment for beta-thalassemia, a rare condition that impairs the production of hemoglobin, the oxygen-carrying protein in red blood cells. Bluebird is now asking the Food and Drug Administration to approve its therapy for adults and children with beta-thalassemia who need regular transfusions of red blood cells.
• Beti-cel is already cleared for market in Europe, where it's sold under the brand name Zynteglo. Bluebird has been trying to reach the same end in the U.S., but it's run into several obstacles. The company disclosed early last year, for example, that the FDA wanted more information about beti-cel before it would accept an approval application, a stance which stunted Bluebird's plans.

Dive Insight:

U.S. approvals are more important than ever for Bluebird, as the company announced in August plans to wind down its European business.

That decision was shaped by the challenges faced while trying to sell Zynteglo. Bluebird set the therapy's initial price at $1.8 million, making it one of the world's most expensive medicines and a lightning rod for criticism. Pushback from government payers in Europe, coupled with manufacturing setbacks, has resulted in very few patients getting treated with Zynteglo and, in turn, Bluebird recording immaterial revenue from the therapy.

"European payers have not yet evolved their approach to gene therapy in a way that can recognize the innovation and the expected life-long benefit of these products," Andrew Obenshain, Bluebird's president of severe genetic diseases, said in an Aug. 9 statement.

Bluebird may run into similar problems in the U.S., though stateside insurers have previously covered high-priced medicines for diseases with few treatment options. In one more recent example: Zolgensma, the Novartis gene therapy for a rare neuromuscular disorder, carries a list price of $2.1 million, yet the treatment is generally covered for eligible patients.

Before it comes to the U.S. market, though, beti-cel must get the FDA's stamp of approval.

Bluebird's application includes data from four clinical studies, two of which are Phase 3 trials. Altogether, these studies offer 220 patient-years worth of data and, as of March 9, span 63 pediatric, adolescent and adult patients of various genotypes who've been treated with beti-cel.

Should beti-cel ultimately come to the U.S. market, it would join a short list of available therapies for beta-thalassemia. It wasn't until 2019 that the FDA first approved a drug, Celgene's Reblozyl, to treat anemia in adult patients with beta thalassemia who require regular red blood cell transfusions.

The National Organization for Rare Disorders estimates that approximately 1 in every 100,000 people in the U.S. have beta-thalassemia, though rates appear higher in other areas of the world like the Mediterranean, Middle East, Africa and parts of Asia.

An OK for beti-cel would also add to the list of approved gene therapies for inherited diseases, following Spark Therapeutics' Luxturna and Zolgensma. Other companies are also working on gene replacement and gene editing therapies for beta-thalassemia and the related blood disorder sickle cell.