Bluebird Bio’s development of a gene therapy to treat transfusion-dependent β-thalassemia (TDT) has been far from easy, but the final path to market is finally coming into view for the 27-year-old company.

On Friday, the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) issued a positive opinion (PDF) on the product, Zynteglo (formerly LentiGlobin), setting up a likely approval from the European Commission during the second quarter. The European Commission generally follows the CHMP’s recommendations.

Zynteglo is designed to add functional copies of an altered form of the β-globin gene into TDT patients’ own blood stem cells. The inserted genes then produce hemoglobin at normal levels, reducing or eliminating the need for the frequent blood transfusions that TDT patients generally receive. The positive CHMP decision "is a crucial step toward providing what would be the first one-time gene therapy for people living with TDT," said David Davidson, M.D., Bluebird’s chief medical officer, in a statement.

If Zynteglo is given the green light in the EU in the second quarter as predicted, it will be Bluebird’s first marketed product—and a major achievement in a multiyear development program marked by a fair share of disappointments.

In 2015, data from an early trial of the product showed wide variations in responses, which raised questions about whether the gene therapy was really that effective. So the company changed the manufacturing process, as well as the protocol for preparing patients for the therapy.

The value of those changes showed last summer, when Bluebird presented data from a phase 1/2 trial of Zynteglo at the European Hematology Association conference. The data showed that the therapy cuts the sickling of red blood cells—a hallmark of TDT—by 30% to 60%, which Bluebird considered to be above the threshold of a clinically significant response.

Bluebird has told investors to expect it will file for FDA approval of Zynteglo by the end of this year. It hasn’t announced pricing for either the U.S. or Europe yet, but the company has suggested that the "intrinsic value" of the product is $2.1 million.

At the J.P. Morgan Healthcare Conference in January, Bluebird said it is developing a reimbursement model for the gene therapy that might include an upfront fee and installment payments spread over five years.

No doubt pricing will be a matter of intense focus as Bluebird moves closer to becoming a commercial-stage biotech. But Wall Street analysts are clearly expecting the company to find pricing solutions that will drive its growth without alienating insurance companies, not to mention U.S. legislators who are fixated on high drug prices.

Analysts at Jefferies estimate that sales of Zynteglo in thalassemia will peak at $696 million in 2026. Bluebird is also testing the product in sickle cell disease, and if it works, sales could hit $1.1 billion in that indication in 2027, Jefferies estimates.

SVB Leerink analyst Mani Foroohar, who issued a note to investors after the CHMP announced its positive opinion, has similar peak sales estimates for Zynteglo. Foroohar noted that Bluebird will be holding an analyst event on May 9, during which it will be expected to provide more details on pricing plans for the product, as well as the "tempo of launch and the rollout of qualified treatment centers in the EU."

Bluebird has been preparing for a steep growth curve, investing $80 million in its first gene therapy manufacturing facility in Durham, North Carolina. It’s designed to produce clinical supplies of the lentiviral vector that’s a key element of gene and cell therapies, but it will be able to scale up to handle commercial production as soon as a Bluebird product candidates wins approval in the U.S. Bluebird has a European manufacturing agreement with Novasep to produce gene therapies at a site in Gosselies, Belgium.

Several physicians who treat TDT in Europe hailed the positive CHMP decision.

"The present management of TDT, including regular blood transfusions every two to four weeks and daily iron chelation therapy has many psychological and social consequences, including marginalization and isolation," said Androulla Eleftheriou, executive director of the Thalassaemia International Federation, in the statement from Bluebird.

The potential approval of the gene therapy product, she added, "brings hope that we can dramatically change the course of this disease and the health and quality of lives of patients with TDT."

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