CALD Gene Therapy Granted “Breakthrough Therapy Designation”
Reporter: Irina Robu, PhD
Bluebird Bio’s Lenti D has been granted as “breakthrough therapy designation” by FDA for the treatment of patients with cerebral adrenoleukodystrophy (CALD), or Lorenzo’s Oil disease due to optimistic data from current ongoing Phase 2/3 study. This therapy contains using patient’s own immature bone marrow cells and modifying them to include a functional copy of ABCD1 gene which permits the expression of functional ALD, the deficient protein in the patient population.
In addition, the data indicated that the safety profile of Lenti-D remains consistent with myeloablative chemotherapy and no graft versus host disease or treatment related mortality were reported. Initial findings from the ongoing Starbeam Study (ALD-102) assessing the investigational gene therapy in boys with CALD aged 17 years or younger who do not have a matched sibling donor were published in the New England Journal of Medicine in October 2017 and indicated that the drug hit its main effectiveness endpoint. In the study, 88% (n=15) of patients infused with Lenti-D remained alive and free of major functional disabilities at 2 years post-treatment.
According to Mohammed Asmal, Vice President, Clinical Development at bluebird bio “The mechanism by which this would work is very much like how stem cell therapy transplantation is able to correct the disease. The theory was certainly there, it just relied on someone, essentially, being willing to develop the vector and then try it on patients who did not have any other feasible options for transplant, and who had poor predicted outcomes for transplant survival.”
Currently, the only available therapeutic option for patients with CALD is allogeneic hematopoietic stem cell transplant (HSCT). Whereas clinical benefit has been reported if made early during CALD progression, possible complications of allogeneic HSCT can be fatal. According to David Davison, chief medical officer at Bluebird Bio “FDA’s Breakthrough Therapy designation for Lenti-D brings new hope to the patients and families affected by this devastating disease”.
SOURCE
https://patientworthy.com/2018/05/29/gene-therapy-ald-breakthrough-therapy-fda/
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This is very insightful. There is no doubt that there is the bias you refer to. 42 years ago, when I was postdocing in biochemistry/enzymology before completing my residency in pathology, I knew that there were very influential mambers of the faculty, who also had large programs, and attracted exceptional students. My mentor, it was said (although he was a great writer), could draft a project on toilet paper and call the NIH. It can’t be true, but it was a time in our history preceding a great explosion. It is bizarre for me to read now about eNOS and iNOS, and about CaMKII-á, â, ã, ä – isoenzymes. They were overlooked during the search for the genome, so intermediary metabolism took a back seat. But the work on protein conformation, and on the mechanism of action of enzymes and ligand and coenzyme was just out there, and became more important with the research on signaling pathways. The work on the mechanism of pyridine nucleotide isoenzymes preceded the work by Burton Sobel on the MB isoenzyme in heart. The Vietnam War cut into the funding, and it has actually declined linearly since.
A few years later, I was an Associate Professor at a new Medical School and I submitted a proposal that was reviewed by the Chairman of Pharmacology, who was a former Director of NSF. He thought it was good enough. I was a pathologist and it went to a Biochemistry Review Committee. It was approved, but not funded. The verdict was that I would not be able to carry out the studies needed, and they would have approached it differently. A thousand young investigators are out there now with similar letters. I was told that the Department Chairmen have to build up their faculty. It’s harder now than then. So I filed for and received 3 patents based on my work at the suggestion of my brother-in-law. When I took it to Boehringer-Mannheim, they were actually clueless.