Positive outcomes for Lenti-D trial, bluebird chasing regulatory approvals
Long-term results from the Phase 2/3 Starbeam study (ALD-102/LTF-304) focused on patients with Cerebral Adrenoleukodystrophy (CALD) were presented at the recent virtual meeting of the European Society for Blood and Marrow Transplantation (EBMT 2020).
Eighty-seven percent of patients in the Phase 2/3 Starbeam study of Lenti-D are alive and free of major functional disabilities (MFDs) at 24 months or more of follow-up. Importantly, there were no reports of graft failure, graft rejection, or graft-versus-host disease (GVHD), noted bluebird.
And 31 out of 32 CALD patients in ALD-102 had stable neurologic function scores following treatment with the company's candidate ALD cell therapy.
ALD is a rare, X-linked metabolic disorder that is estimated to affect one in 21,000 male newborns worldwide.
CALD is a type of adrenoleukodystrophy (ALD), a serious neurological disorder caused by mutations in the ABCD1 gene. Stem cell therapy is the current standard of care for those in the early stages of the disease. Although it cannot repair the damage already done, it can in some cases prevent further damage. Not all patients can receive stem cell transplants.
There are also a number of experimental treatments under development - gene therapy is a modification of stem cell therapy, which allows transplantation of the patient’s own cells following a genetic correction of the disease-causing mutation. Lenti-D is such a treatment.
There are associated risks with stem cell transplantation (allo-HSCT) including transplant-related mortality, graft failure or rejection, and GVHD.
The Phase 2/3 Starbeam study (ALD-102) for that therapy has completed enrollment and is longer recruiting, said bluebird bio. As regards further trial work being undertaken in relation to Lenti-D, a company spokesperson told us:
“We are currently enrolling patients for a Phase 3 study (ALD-104) designed to assess the efficacy and safety of eli-cel after myeloablative conditioning using busulfan and fludarabine in patients with CALD.
“In ALD-102 and ALD-104, patients are followed for two years post-eli-cel infusion. After they have completed the primary study - 24 months after infusion with eli-cel - they will be asked to participate in the long-term follow-up study, LTF-304.
“In the long-term study, patients will be evaluated every six months through five years after drug product infusion, and then annually, thereafter, through 15 years following infusion.”
Bluebird bio is currently on track to submit a Marketing Authorization Application (MAA) in the EU for Lenti-D for CALD by year-end 2020, and a Biologics License Application (BLA) in the US in mid-2021.
“We cannot speculate on timing of regulatory decisions,” commented the bluebird representative when pressed on likely commercial timelines.
In May, the company signed a deal with Hitachi Chemical Advanced Therapeutics Solutions and Apceth Biopharma, both subsidiaries of Hitachi Chemical Company, for an expanded, long-term development and manufacturing agreement for a range of its therapies including Lenti-D.
“Our partnership with Hitachi Chemical is a significant example of our continued progress as we work to bring transformative therapies to patients in need,” said the spokesperson.
Citing the fact that its applications have not yet been submitted, the company also declined to comment on existing or potential Lenti-D manufacturing capacity.