Andrew Obenshain officially took over as bluebird bio’s CEO when the company split into two back in November. But there’s one item from his prior desk that's still on his mind: the removal of Zynteglo from the European market.
“That was one of the hardest decisions,” Obenshain told Fierce Pharma on the virtual sidelines of the annual J.P. Morgan Healthcare Conference. “It certainly ran against everything we stand for, which is getting the products to the patient.”
Obenshain would not, of course, say when or if bluebird bio might try to get Zynteglo back to Europe. The company has begun the process to withdraw (PDF) the marketing authorization with regulators there and operations have officially been wound down in the region. But as work for the treatment moves on with a focus on the U.S. market, some projects in the works could boost scalability that could ultimately help if they do opt to return in the future.
Zynteglo is an ex vivo gene therapy, meaning cells are taken from the patient, boosted in a lab and then returned to the patient later. Patients’ cells are collected and must be shipped to a manufacturing plant within 48 hours. So, bluebird is working on improving the cryopreservation process, called cryopreserved apheresis, which could allow the company to expand the patient population it already serves.
That could ultimately help bluebird reenter Europe while keeping manufacturing in the U.S., but the company has no plans as of now to do so.
“It's off the table for now until we bring down the delivery costs of the therapy and get some scale,” he said.
Obenshain, who has been helming the company for a bit longer than that November cutoff as the 2seventy bio spinout was underway last year, spoke as bluebird is expecting two regulatory decisions with a new, slimmed-down operation that is “laser focused” on those regulatory milestones.
And yet, that Europe decision still stings. “That is unfinished business for myself,” Obenshain said of the European market. “I'm also the one that made the decision to withdraw from Europe.”
Once the therapy is approved for beta thalassemia, an FDA decision due by May 20, Obenshain expects bluebird will be able to provide a much higher volume and therefore scale.
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Obenshain joined bluebird in 2016 as head of Europe before becoming president of the severe genetic diseases unit. Then bluebird spun out its oncology operations into 2seventy bio, and he moved into the CEO role for the rare-disease-focused company.
That means he was at the head of negotiations when bluebird opted to remove the blood disorder gene therapy from the European market last year. He said the company and regulators simply failed to come to an agreement on fair pricing and market access. Zynteglo was approved in the region in June 2019 for beta thalassemia and was priced at $1.8 million for the one-and-done treatment.
Obenshain said the discussions began in Germany, where regulators quoted them 630,000 euros, which would not cover the cost of production and delivering the therapy to patients in Europe.
“We simply couldn’t make the math work,” he said.
Bluebird tried to find partners to help mitigate the costs, but the math still didn’t add up. So for now, Obenshain said they are treating nine patients in Germany who had already signed up to receive the therapy when the discussions broke down—which shows that the patient demand was there.
The U.S. market, meanwhile, is different, and payers recognize value, according to Obenshain. Zynteglo is being considered by the FDA right now for beta thalassemia, under the name beti-cel. The CEO said the gene therapy can reduce hospital visits, which takes some of the burden off the medical system.
RELATED: Bluebird bio hits FDA clinical hold—again—for gene therapy in sickle cell disease
That means bluebird has a jam-packed 2022 ahead. The company has long been focused on drug development, but now Obenshain says it's shifting gears into a commercial organization. The FDA is also nearing a decision for a cerebral adrenoleukodystrophy gene therapy, which is due on June 17.
“It's been a long wait for a lot of gene therapies. It's finally here,” the CEO said. “We're in a different phase of the company. Historically, we're doing tough science things. Science doesn't follow timelines.”
That couldn’t be more true for bluebird’s ongoing work with lovo-cel, the treatment formerly known as LentiGlobin, which is inching toward the FDA for sickle cell disease and has had several bumps along the way. In late December, the treatment was placed on a clinical hold for pediatric patients after a patient experienced a “persistent, nontransfusion-dependent anemia.” That hold came a few months after the FDA lifted a hold on the treatment in sickle cell and beta thalassemia.
Treatment of adult patients has continued. Obenshain said they already have the data they need for an approval application with the FDA, but the ongoing trials are aiming to prove comparability on the manufacturing side.
The FDA—so far—has not provided questions surrounding the hold, which bluebird needs to form its response. Bluebird was originally planning to file the therapy in the first quarter of 2023, and, “out of an abundance of caution, we’re not going to re-up that” right now until the questions are received from the agency, Obenshain said. In a release issued ahead of bluebird's J.P. Morgan presentation Wednesday, the company said that they are examining what, if any, impact the ongoing partial clinical hold may have on that 1Q 2023 timeline.
RELATED: Bluebird’s Zynteglo safety snag could spell trouble for other gene therapies: analysts
Amid broader discussions at the FDA around gene therapy safety, Obenshain believes that one thing that sets bluebird apart is the company’s ability to track the DNA changes or gene insertions made by its therapies. Traceability is key to safety in the field, but it’s also allowed bluebird to respond quickly to FDA inquiries and the clinical trial holds.
“That's where the FDA starts to get very nervous, is when you can’t actually explain what is happening with what you're doing,” Obenshain said.
Editor's Note: This story was updated on 1:25 p.m. ET on Jan. 1, 2022, to reflect that bluebird is awaiting an approval in beta thalassemia, not sickle cell disease. Additional context on the Europe withdrawal was also added.