Bluebird Bio’s $1.8 million gene therapy Zynteglo is the latest such therapy to suffer from manufacturing issues, causing a delay to its EU launch.
The European Medicines Agency (EMA) approved orphan drug Zynteglo (autologous CD34+ cells encoding βA-T87Q-globin gene) – previously known as LentiGlobin – as a one-off treatment for beta-thalassaemia in June. Developer Bluebird Bio has priced the therapy at €1.58 million ($1.8 million).
However, a setback due to manufacturing problems means Bluebird is delaying launch to at least 2020.
Specifically, Bluebird lacks “manufacturing readiness,” SVB Leerink analyst Mani Foroohar said, commenting on the firm’s post-approval presentation at the European Hematology Association (EHA) Congress.
“Like any cell therapy [sic], ‘process is the product’ for Zynteglo, and whether the ultimate commercial product will live up to the clinical data seen to date is unclear due to necessary manufacturing changes,” he wrote. “More concerning is that Bluebird was unable to execute on the manufacturing process development that is the critical core competency of any cell therapy franchise.”
In a follow-up note, Foroohar said: “While the high price-point of Zynteglo is a tailwind for the company, the unanticipated delay due to required changes to manufacturing processes introduces new uncertainty into the Zynteglo launch and execution across the broader Bluebird Bio platform,”
Bluebird did not respond when contacted by this publication for more information on the manufacturing problems.
Rushing to get ahead
In the autologous cell and gene therapy space, Bluebird is not alone in being tripped up by manufacturing problems.
Speaking to Bioprocess Insider at Phacilitate 2019, Dominik Clark, global head of Cell Therapy at supplier of human-derived biological products firm Hemacare, said that in these pioneering days of cell and gene therapies “everyone is rushing to get ahead,” and “inevitably there will be problems.”
In 2018, Novartis identified some issues in the manufacturing of Kymriah (tisagenlecleucel), the first marketed chimeric antigen receptor (CAR) T-cell therapy, centered around the variability in the product’s specifications for its diffuse large B-cell lymphoma (DLBCL) indication.
And before that, Provenge (sipuleucel-T) – an autologous cell therapy initially approved in the US in 2010 for the treatment of prostate cancer – suffered from a complex and costly manufacturing and administrative process leading to its developer Dendreon filing for bankruptcy in 2014.
It is “not necessary that the product failed, just the manufacturing challenges of having stability and making them available to the patients which added complexity,” Clark told us.
“We’re learning valuable lessons from Novartis to look at that process and as the next generations come through, we will all learn and improve from this,” he continued. “We know we are going to see some issues because you can only test so many patient products before you go commercial, because of that variability.”
However, he continued, for curative and sometimes last hope medicines, a product being slightly out-of-spec is not the end of the world.
“The worst case is it’s not as good as it could have been but it’s still [patients’] only product and their only chance, so there lies the difference between some other industries: there are no alternative.”