Phase II/III Starbeam study of Lenti-D shows efficacy in cerebral adrenoleukodystrophy.- bluebird bio

bluebird bio announced updated results from the clinical development program for its investigational Lenti-D gene therapy in patients with cerebral adrenoleukodystrophy (CALD). The Phase II/III Starbeam study (ALD-102) is assessing the efficacy and safety of Lenti-D in boys 17 years of age and under with CALD. Updated data from the ongoing observational study (ALD-103) of allogeneic hematopoietic stem cell transplant (allo-HSCT) in boys 17 years of age and under with CALD were also presented. Of those patients who have or would have reached 24 months of follow-up and completed the study, 88 percent (N=15/17) continue to be alive and MFD-free in a long-term follow-up study. The 14 patients currently on study have less than 24 months of follow-up and have shown no evidence of MFDs. The longest follow-up of the additional 14 patients was 20.4 months.

Three out of the 32 treated patients did not or will not meet the primary efficacy endpoint; two patients withdrew from the study at investigator discretion, and one experienced rapid disease progression early on-study resulting in MFDs and death. Secondary and exploratory efficacy outcomes included: changes in neurologic function score (NFS), a 25-point score used to evaluate the severity of gross neurologic dysfunction across 15 symptoms in six categories; resolution of gadolinium enhancement (GdE), an indicator of active inflammation in the brain; and change in Loes score, an MRI measurement of white matter changes in CALD. Of the 32 patients treated, 30 had stable NFS following treatment with Lenti-D, defined as NFS less than 4, without a change of more than 3 from baseline. Loes scores generally stabilized within 12-24 months and GdE+ enhancement resolved in most patients following Lenti-D treatment.

The primary safety endpoint is the proportion of patients who experience acute (at least Grade 2) or chronic graft-versus-host disease (GvHD) by Month 24. GvHD is a condition that may occur after an allo-HSCT, where the donated cells view the recipient�s body as foreign and attack the body. No events of acute or chronic GvHD have been reported post-Lenti-D treatment and there have been no reports of graft failure, cases of insertional oncogenesis, or replication competent lentivirus. The safety profile of Lenti-D is generally consistent with myeloablative conditioning with busulfan and cyclophosphamide, the standard preparative regimen completed prior to HSCT.Data were presented at the 13th European Pediatric Neurology Society (EPNS) Congress.