Bluebird bio may finally get a gene therapy approved in the US
Bluebird bio may, at long last, get a gene therapy approved in the US.
The Cambridge, MA biotech announced Monday that the FDA had accepted and given priority review for Zynteglo, its gene therapy for the rare blood disorder beta-thalassemia. The announcement sets up an expedited FDA decision by May 20, 2022.
A priority review doesn’t guarantee approval, and more than a few recent biotechs have been spurned after receiving the designation, including Incyte, Sesen, and Provention. But it represents a substantial step forward for a therapy that has seen repeated setbacks and a company that not long ago had an application slapped down with a refuse-to-file letter.
The approval rate for candidates given FDA priority review hovered between around 70% and 90% between 2011 and 2019, compared to a little over 60% for drugs given the 10-month standard reviews.
The acceptance is a long time coming for bluebird. The company showed its first results from a Phase III trial in beta-thalassemia back in June 2017 and it first won conditional approval in Europe in June 2019. Bluebird at the time also showed dramatic data on a similar one-time treatment for sickle cell disease, and then-CEO Nick Leschly said the company planned to launch the therapy for beta-thalassemia in 2020 and for sickle cell disease in 2022.
But the company then faced repeated delays for both candidates, struggling to finalize its manufacturing process or reach an agreement with regulators on how best to measure the quality of its product. Bluebird’s arc became a parable for the importance of manufacturing in gene therapy, where treatments are so technically complex that reliably producing it at scale can be as sophisticated a challenge as proving it works.
The delays appeared to be part of what pushed the company to split into two, spinning off its cancer division to a biotech called 2seventy, so bluebird could put most of its resources behind getting its gene therapies for rare genetic diseases approved.
Beta-thalassemia, affecting about 1 in 100,000 Americans, isn’t expected to be a huge market for bluebird in the US. But an approval would be a key step toward bluebird delivering on the promise it’s flashed for years.
It’s particularly important after the biotech decided to withdraw Zynteglo, along with the rest of its gene therapy portfolio, from the European market, where there is a significantly larger population of beta-thalassemia patients. The company said European governments were unwilling to pay a fair price for the treatment.
In Germany, the only country for which bluebird has disclosed details, authorities offered $790,000 for the one-time treatment, with the payout moving to $950,000 if the therapy is still working after five years. The figures are roughly in line with the $900,000 price tag analysts expected bluebird to put on the therapy prior to launch. Bluebird wanted $1.8 million paid over 5 years, with payouts conditioned on a patient’s response.
A spokesperson for bluebird, alluding to the company’s turbulent history with pricing, said the company has not yet set a price for Zynteglo in the US and won’t comment on payment structure.
”We’ve learned firsthand there is no one-size-fits-all approach to access and reimbursement for gene therapy and are willing to try a number of payment structures that respond to the unique needs and priorities of patients, providers and payers without creating added barriers or complexities,” she said.
She added that “several” patients had been dosed with Zynteglo prior to its withdrawal in Europe and several more who had already consented to treatment will still receive it. Rollout there was disrupted by manufacturing delays and an (ultimately not born out) safety scare; bluebird said in quarterly filings it began receiving revenue from the drug but that the revenue was “immaterial.”
A US approval would make Zynteglo the third gene therapy approved in the US, after Spark’s Luxturna and Novartis’ Zolgensma. It would be the first approved ex-vivo gene therapy, where cells are removed from a patient, modified and then reinfused — as opposed to in vivo gene therapies, where a patient’s cells are modified directly in their body.
Although not a universal cure, Zynteglo has proven a highly effective treatment for beta-thalassemia, a disease marked by monthly blood transfusions that can be debilitating over time. Out of 36 evaluable patients in the company’s trials, 32 no longer needed transfusions for at least 12 months.