FDA scuttles bluebird's accelerated plans for sickle cell gene therapy, as higher CMC bar forces 1-year delay
In yet another smudge on bluebird bio’s track record for execution, the biotech is pushing back the filing for its gene therapy in sickle cell disease by a year due to a new data requirement from the FDA.
With the setback, bluebird joins a league of gene therapy developers — from BioMarin to Voyager — that have been hampered by CMC issues. While somewhat unexpected, the regulators’ request highlights their stringency around manufacturing and quality control.
According to bluebird, while the FDA is happy to base its review on promising data from Group C of the HGB-206 study, it wanted more information on the refined manufacturing process the biotech is planning to use for the commercial batch of bb1111. In short, bluebird will need to prove “analytical comparability” as it transitions from clinical-grade to commercial-grade manufacturing.
“(FDA) requested the use of drug product manufactured from sickle cell disease (SCD) patient cells in addition to healthy donors as well as commercial lentiviral vector to demonstrate drug product comparability,” the company noted.
That requires bluebird to get drug product from its commercial contract manufacturing organization, which is itself experiencing 4 to 6 month delays related to Covid-19. Once they secure a slot, the whole process is expected to take 6 months — meaning the BLA filing will happen in late 2022 the earliest.
The implications of this delay will reverberate across bluebird’s entire pipeline, wrote Yaron Werber at Cowen.
“As BLUE is a SCD story longer-term, this puts pressure on ide-cel’s launch in Q2:21 to perform,” he wrote, adding: “The FDA’s request in SCD appears unlikely to impact the filing in TDT which remains on track for mid-’21.”
Both the sickle cell disease and transfusion-dependent beta-thalassemia programs are built upon LentiGlobin, which delivers a functional copy of the HBB gene into a patient’s own hematopoietic stem cells using a lentiviral vector.
Despite nabbing approval in Europe for TDT last June, the company postponed the launch until the beginning of 2020 in order to finalize commercial specifications. Marketed as Zynteglo in Europe, the gene therapy has yet to treat its first commercial patients. The pandemic has held it back even more, alongside a US filing originally planned for earlier this year.
“When asked if different disease characteristics of SCD vs TDT trigger this level of complexity of regulatory path, mgmt agreed upon and also brought up scale-up of manufacturing for larger market oppy of SCD as another factor, and the need to transition to a more commercial friendly process in SCD,” Jefferies’ Biren Amin noted.
But manufacturing struggles have long been an issue at bluebird. Back in March the agency had also punted back an application for ide-cel, the BCMA CAR-T partnered with Bristol Myers Squibb via Celgene, because of a faulty section on CMC. The teams have since refiled and scored priority review.
Some investors, though, are not waiting around for bluebird to figure out the sickle cell program. Shares $BLUE tumbled 13.63% pre-market to $ 50.57.