Once again, manufacturing concerns are delaying access to a new, highly anticipated, and very expensive gene therapy. Bluebird Bio, which this month got conditional European approval for its first gene therapy, says the launch will not occur until 2020 because regulators required it to "tighten up" its manufacturing before treating its first commercial patient.
The news of the delay beyond analyst expectations was overshadowed on Friday by Bluebird’s announcement that it would price Zynteglo in Europe at €1.575 million ($1.77 million), a cost that is amortized over five years and only if it works on patients treated for transfusion-dependent beta-thalassemia. The delay was first reported by Biopharma Dive.
“We have strong momentum and our plans for launch are well under way. At the same time, we are working in collaboration with the EMA to finalize and narrow commercial drug product specifications and our commercial drug manufacturing process,” Bluebird Chief Commercial Officer Alison Finger said Friday, according to a recording of the investor call. “We have agreed to evaluate our drug specifications following our conditional approval and we have decided to tighten our drug product specifications and manufacturing process prior to treating our first commercial patient.”
She said the company will work on the changes in “parallel” while also qualifying and training the staff and facilities that will handle the treatments. She said Bluebird expects to have the first patients enrolled by the end of the year and to begin treatments in early 2020.
"Post approval conditions are common for advanced therapies of this nature, like Zynteglo, given the complexities of these products,” Finger said.
It was always assumed that manufacturing of these kinds of treatments would be tricky because of the exacting procedures needed to genetically code a patient’s cells. The processes require that cells be taken from a patient, cryopreserved, and shipped to a facility where they are genetically reprogrammed and new cells manufactured in the lab. They are then shipped back for infusion into the patient, all in the shortest time possible.
Novartis’ initial jump into gene therapies with pioneering CAR-T drug Kymriah for acute lymphoblastic leukemia ran into manufacturing difficulties from the get-go. Real-world product has not always matched the specifications the FDA required on the label for cell variability. The company hopes to convince the FDA to change the drug’s label to be more in line with the specifications it has seen in the clinical setting so that it can be provided to more patients.
Meanwhile, the manufacturing issue has slowed expansion in the U.S. because Novartis is confining use to certain pediatric and young adult patients. The one-time treatment produced just $45 million in sales in the first quarter despite its list price of $475,000.
Bluebird Bio’s manufacturing journey has had its own twists and turns. It tweaked its processes after early data for the drug showed a highly variable response to treatment that made it difficult to analyze its effectiveness. Patients treated with the drug produced since Bluebird altered its initial manufacturing process started showing the kinds of results that led to European approval.
Bluebird has infrastructure ready to go for the launch. It is using Apceth's site in Munich, Germany, to produce Zynteglo in Europe. In the U.S., where it expects a 2020 approval for the treatment, it is qualifying an $80 million, 125,000-square-foot lentiviral vector facility in Durham, North Carolina. It will also work with a couple of CDMOs in the U.S.