Anyone up for a lottery ticket biotech play? I mentioned this one before, but this week is game time with the FDA. Bluebio has been crushed with countless delays. The stock is so beaten down that if they get approvals in a few months, it may 5x or more very quickly. Or if the FDA denies them again, they may go to $0. LOL!
Update article:
bluebird bio Blazes Trail for Lentiviral Vectors at Upcoming FDA AdComm | BioSpace | June 6, 2022
For the first time in half a decade, the U.S. Food and Drug Administration’s Cellular, Tissue and Gene Therapies Advisory Committee will convene June 9-10 to address two therapies developed by bluebird bio in back-to-back meetings sure to draw the eyes of all companies developing lentiviral vectors as potential therapeutics for rare diseases.
For Cambridge, MA-based bluebird, the two-day meetings will be a huge moment in a watershed year for the beleaguered company that laid off nearly one-third of its employees in April. Not only will the advisory committee help shape the future for beti-cel and eli-cel, gene therapies that are already marketed in Europe, it could likely shape the future of the trailblazing company.
“Next week is going to be monumental, quite frankly,” Melissa Bonner, head of research at bluebird bio told BioSpace. “This is the first time a lentiviral vector will be considered in the United States. This will have a profound impact on the entire field of gene therapy because there are a lot of different products in development that use an LVV approach.”
Like a spelunker carefully exploring a newly-discovered cave, the bluebird team, along with the scientists who make up the advisory committee, will be navigating new regulatory territory in gene therapy. Because the discussions that will be had this week as eli-cel and beti-cel are carefully examined will have ripple effects across the industry, Bonner predicted the committee meeting will be closely watched by other companies following a similar program path.
“Everyone will tune in with their popcorn to see how this is going,” she quipped.
Eli-cel, also known as elivaldogene autotemcel, will be the first bluebird program discussed by the advisory committee. Eli-cel was previously approved in Europe under the brand name Skysona. It was approved last year as a treatment for juvenile patients with early cerebral adrenoleukodystrophy (CALD), a serious neurological disorder caused by mutations in the ABCD1 gene. CALD typically develops in a juvenile around the age of 7. The rare, progressive, x-linked disorder is ultimately fatal but not before sending the patient into a vegetative state.
Eli-cel uses ex vivo transduction with the Lenti-D lentiviral vector to add functional copies of the ABCD1 gene into a patient’s own hematopoietic stem cells (HSC). The addition of the functional ABCD1 gene allows patients to produce the ALD protein, which is thought to facilitate the breakdown of very long-chain fatty acids, which cause the breakdown of myelin, the protective sheath around nerve cells in the brain.
Throughout the course of its development, eli-cel has shown positive efficacy. But, at the same time, there have been some safety concerns, which the FDA advisory committee members will likely discuss in detail. The eli-cel study was hit with a clinical hold last year over safety concerns after a patient treated with the gene therapy developed a rare form of cancer, myelodysplastic syndrome.
Bonner said the company has been transparent about the safety of eli-cel. Throughout its development, three patients developed a malignancy that was likely related to the gene therapy. Bonner said the safety issues will have to be weighed against the overall positive efficacy seen throughout clinical development. The advisory committee members are expected to “have a lively discussion” to determine if the overall benefits of eli-cel outweigh the risks in a patient population that has few options beyond an allogeneic stem cell transplant from a matched donor.
“If you have a matched donor, your odds are good. If not, your odds are very different,” she said. “This is a life-saving therapy. We think there’s a positive benefit-risk.”
On day two, the advisory committee will assess beti-cel, which is being developed for the blood disorder beta-thalassemia. Beti-cel is marketed as Zynteglo in Europe. Pointing to the clinical data, Bonner said with beti-cel there have not been the same safety concerns seen with eli-cel, and also noted that it has had positive efficacy data that she called “transformative.” Beti-cel is one-time gene therapy intended to treat beta-thalassemia in patients who need regular transfusions of red blood cells. In Phase III trials of beti-cel, 89% of patients who could be evaluated achieved transfusion independence.
As the advisory committee meeting looms closer, Bonner said the bluebird team will prepare as well as possible for all potential questions brought up by the committee members. While the meeting is a new experience for bluebird, Bonner noted this is also a new experience for the advisory committee members who have not met since the 2017 meeting before the approval of Spark Therapeutics’ Luxturna, a gene therapy for a rare form of blindness.
Although Bonner admitted the advisory committee meetings are stress-inducing, especially given the recent layoffs at bluebird, she shared her hope for the vast potential gene therapies have for rare disease patients. There are approximately 7,000 known rare diseases that impact between 25 million and 30 million Americans. The vast majority of those rare diseases do not have any therapeutic options or have insufficient ones.
“This type of technology (lentiviral vectors) can be pretty useful for these patients. That’s why this will be such a momentous occasion,” she said.
Update on BLUE. Day 1 went very well. Hmm.....
FDA Advisory Committee Unanimously Endorses eli-cel Gene Therapy for Cerebral Adrenoleukodystrophy | bluebird bio | June 9, 2022
If approved, eli-cel will be the first and only gene therapy for the treatment of early active CALD, a rare neurodegenerative disease that primarily affects young children and leads to irreversible loss of neurologic function and death
PDUFA goal date is set for September 16, 2022
bluebird bio, Inc. (Nasdaq: BLUE) today announced the outcome of the U.S. Food and Drug Administration’s (FDA) Cellular, Tissue, and Gene Therapies Advisory Committee (CTGTAC) discussion of elivaldogene autotemcel (eli-cel) for the treatment of early active cerebral adrenoleukodystrophy (CALD) in patients less than 18 years of age who do not have an available and willing human leukocyte antigen (HLA)-matched sibling hematopoietic stem cell (HSC) donor.
On the question “Do the benefits of eli-cel outweigh the risks, for the treatment of any sub-population of children with early active cerebral adrenoleukodystrophy (CALD)?” the CTGTAC voted 15 (yes) to 0 (no).
“For decades, the CALD community has fought for the opportunity to stave off the rapid, irreversible decline associated with this devastating disease,” said Andrew Obenshain, chief executive officer, bluebird bio. “Today we are one step closer to delivering a potentially lifesaving therapy for CALD. We are grateful to the families, clinicians and committee members who participated in today’s advisory committee discussion and remain committed to working with the FDA as it completes its review of the eli-cel Biologics License Application.”
CALD is a rare, progressive, neurodegenerative disease that primarily affects young boys and causes behavioral, cognitive, and neurological deficits. Nearly half of patients who do not receive treatment die within five years of symptom onset. Allogeneic hematopoietic stem cell transplant (allo-HSCT) is currently the only effective treatment option but is associated with serious potential complications and mortality that increase in patients without a matched sibling donor. If approved, eli-cel will be the first approved gene therapy to address the underlying genetic cause of disease for patients living with CALD in the U.S. – offering the more than 70% of patients diagnosed with CALD who do not have a matched sibling donor an alternative to allo-HSCT.
The committee’s recommendation is based on the Biologics License Application (BLA) currently under priority review by the FDA with a PDUFA goal date set for September 16, 2022. The BLA for eli-cel is supported by efficacy and safety data from the completed Phase 2/3 Starbeam study (ALD-102) (N=32). Additionally, the BLA contains data for 35 subjects dosed in the Phase 3 ALD-104 study. In clinical studies, patients treated with eli-cel were more likely to achieve both overall and event-free survival than allo-HSCT patients without a matched sibling donor, with the clearest benefit for patients without a matched donor of any type.
The eli-cel clinical program was placed on a clinical hold following a Suspected Unexpected Serious Adverse Reaction (SUSAR) of myelodysplastic syndrome (MDS) in August 2021. Consistent with this known risk, two additional cases of MDS have subsequently been reported. All patients who received eli-cel in the clinical program continue to be closely monitored, per study protocols.
The CTGTAC also discussed the overall safety of lentiviral vector (LVV) gene therapies, concluding in a 13 to 1 vote that the safety data from lovo-cel for sickle cell disease is not relevant to the review of eli-cel. In addition to granting eli-cel BLA priority review, the FDA previously granted eli-cel Orphan Drug status, Rare Pediatric Disease designation, and Breakthrough Therapy designation. bluebird bio is eligible to receive a priority review voucher upon potential approval of eli-cel.
Tomorrow, June 10, 2022, the CTGTAC will convene to discuss the efficacy and safety of betibeglogene autotemcel (beti-cel), an investigational LVV gene therapy for patients with beta-thalassemia who require regular red blood cell transfusions.
