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Bluebird, Regulators Map Out Approval Plan For Gene Therapy

Xconomy Boston — 

One of gene therapy’s major unanswered questions is just what it’ll take to convince U.S. regulators to approve one of these treatments. With a gene therapy that’s already produced promising results in a few patients in clinical trials, Bluebird Bio has a chance to pave the way. And today it’s cut a deal with the FDA to figure out how to get that treatment to the regulatory finish line.

Bluebird (NASDAQ: BLUE) said this morning that it’s come to an agreement with regulatory agencies both in the U.S. and in Europe on an approval path for LentiGlobin, its gene therapy for beta-thalassemia, a crippling blood disorder. The agreements map out potential approval on an accelerated basis for the therapy—based on less of a body of data than is typically required.

If Bluebird were to succeed, it would have the chance to own the first gene therapy approved in the U.S., a major milestone for the field. Only Europe has an approved gene therapy, Glybera, from Uniqure (NASDAQ: QURE) for a rare metabolic disorder, and that product hasn’t been launched yet.

Approval is still a ways away, of course. To this point, Bluebird has produced very promising data, but in just four patients. With past gene therapies falling short of expectations in clinical trials, a lot more proof is needed. And then there’s the question of how much LentiGlobin would cost (would it be paid for in one large, lump sum? On an annuity basis?).

Nonetheless, Bluebird has an unusual opportunity in front of it. Here’s what the Cambridge, MA-based company needs to do to get LentiGlobin to market:

In the U.S., Bluebird will have to run two additional trials, called HGB-207 and HGB-208. These are each 15-patient, open-label studies—not placebo-controlled, randomized trials. Adults and adolescents with beta-thalassemia will be enrolled in HGB-207, and children in HGB-208. Bluebird will track these patients’ results for two years, and the goal will be to free the subjects of the blood transfusions they normally require to prevent anemia for 12 months.

Bluebird says that based on its talks with the FDA, data from these two studies and the two existing trials underway (known as Northstar and HGB-205), will form the basis for a regulatory filing. Northstar and HGB-205 are enrolling patients in the U.S. and Europe, respectively, with either beta-thalassemia or sickle cell disease. If LentiGlobin hits its goal, Bluebird believes it could seek accelerated approval, and conduct post-approval long-term follow up studies of these patients.

In Europe, Bluebird has been working with the European Medicines Agency and others, and based on those discussions, believes that it can win conditional approval of LentiGlobin based on the data from HGB-205 and Northstar studies alone. That conditional nod could be converted to a full approval should Bluebird successfully complete HGB-207 and HGB-208, and obtain more long-term follow-up and post-approval monitoring data.

“This feedback brings us closer to achieving our vision of delivering one-time, potentially transformative gene therapy to patients,” Bluebird chief medical officer David Davidson said in a statement.

Bluebird is holding a conference call this morning to discuss the news.

Patients with beta-thalassemia inherit a faulty gene that codes for beta globin, a subunit of hemoglobin, the protein in red blood cells that carries oxygen. Without the ability to make hemoglobin, these patients get severe anemia and need frequent blood transfusions to survive. They also need iron chelation therapy to deal with the iron overload those transfusions cause; that buildup of iron often kills patients.

About 15,000 people in the U.S. and Europe and 280,000 worldwide are estimated to be living with the disorder, and a majority of them have beta-thalassemia major, the severe form, according to Bluebird.

For more about Bluebird’s history, LentiGlobin, and the company’s ongoing gene therapy trials, check out this piece. And for an overview of gene therapy’s ups and downs, see this piece on its battle to cure hemophilia.

Beta-thalassemia is just the start for Bluebird, meanwhile. The company will soon present data from the first test of a gene therapy in a patient with sickle cell, the most common genetic disorder in the world. Investor anticipation that LentiGlobin might successfully treat sickle cell as well as beta-thalassemia has sent Bluebird’s shares skyrocketing this year. Shares closed at $156.40 apiece on Monday. Bluebird priced its IPO at $17 per share in 2013.