LentiGlobin continues to deliver in latest sickle cell update as bluebird outlines path to accelerated approval, despite patient death
Still reeling from the FDA’s stunning refusal to file its CAR-T therapy ide-cel, bluebird is eager to win back some credibility with a new slice of the LentiGlobin data they will be taking to the FDA for an accelerated approval.
To be sure, the BLA submission won’t happen until the second half of 2021 — giving bluebird plenty of time to figure out the manufacturing. But an update presented at the EHA virtual congress has apparently helped them reach “general agreement” with regulators and boosted execs’ confidence.
Building on previously reported data, the presentation centers around Group C of the HGB-206 study, comprising a total of 25 patients who received a gene therapy produced on a “refined manufacturing process that was designed to increase vector copy number (VCN) and improve engraftment potential of gene-modified stem cells.”
Among 14 patients with at least six months of follow-up and a history of vaso-occlusive crises and acute chest syndrome — five more than the last disclosure — the mean reduction in annualized rate of those painful episodes was 99.5%. It marks a slight improvement from the already stellar 99% investigators observed at ASH last December.
These were patients who had a median of eight events in the two years prior to treatment, according to bluebird.
One of the patients who had complete resolution of vaso-occlusive events died suddenly 20 months after treatment, although it was attributed to cardiovascular and other underlying issues and thus deemed “unlikely related” to LentiGlobin.
Zooming out to the 16 who made the six-month cutoff point, median levels of a key biomarker known as gene therapy-derived hemoglobin were maintained and contributed at least 40% of all hemoglobin.
At last visit reported, total hemoglobin ranged from 9.6 – 16.2 g/dL and HbAT87Q levels ranged from 2.7 – 9.4 g/dL. At Month 6 the production of HbAT87Q was associated with a reduction in the proportion of HbS in total hemoglobin. Patients had a median of ≤ 60% HbS. All patients in Group C were able to stop regular blood transfusions and remain off transfusions at three months post-treatment.
What matters most, though, will be the rate of complete resolution of severe vaso-occlusive events at 18 months post-treatment — which bluebird said would cement the planned BLA submission.
Then there’s the commercial manufacturing issues that led to previous delays for the launch of its other EU-approved gene therapy, Zynteglo, and review of ide-cel.
In an earnings call last month, CEO Nick Leschly promised analysts that they have “learned a lot” and are prepared for the transitions into new production methods, including suspension lentiviral vector. “(Q)uite honestly, we would not be signing up for a regulatory time line or range of time line if we didn’t feel that we had the execution infrastructure behind it,” he said.