Bluebird's breakthrough gene therapy Lenti-D is on the market.

Adrenal whiteness malnutrition (adrenoleukodystrophy, ALD) is a deadly, neurodegenerative, X-chain recessive genetic disease with a incidence rate of 0.5 per 100,000 to 1/100,000, most commonly in young boys, affecting approximately 21,000 male newborns worldwide.
ALD is caused by mutations in the ABCD1 gene that cause changes or loss of function of the encoded adrenal white matter malnutrition protein (ALDP), which prevents the patient's extremely long chain of saturated fatty acids (VLCFA) from entering the peroxidase for β-oxidation. Thus accumulated in plasma and tissue cells, leading to mitochondrial dysfunction, oxidative stress, biofilm function destruction, and ultimately caused the nervous system demyelination and adrenal cortical function decline and other pathological changes.
brain-type adrenal white-blood malnutrition (cerebral adrenoleukodystrophy, CALD) is one of the most serious forms of ALD.
about 40 percent of ALD boys develop CALD, and most patients who are responsible for thinking and muscle control have severe loss of nerve function and, if left untreated, progress quickly and eventually die.
CALD is manifested in 6 major human dysfunctions (MFDs), including communication disorders, cortitis (complete loss of vision in both eyes), gastric tube feeding, complete incontinence, wheelchair dependence, and complete loss of autonomous movement, seriously impairing the patient's independent life function.
ALD currently does not have special effects therapy, allo-HSCT is the current clinical alD standard treatment, can correct VLCFA metabolic disorders, improve clinical symptoms, improve long-term survival rate.
However, allo-HSCT requires early treatment to be effective and is difficult to obtain due to the patient's bone marrow matching donor, and the risk of immune rejection, transplant-related death, and anti-host disease of grafts is significantly increased.
gene therapy is considered to be the most promising treatment for ALD.
October 2nd Bluebird announced that the European Medicines Agency (EMA) had formally accepted a listing application for its gene therapy, elivaldogene autotemcel (Lenti-D™, Eli-cel) for the treatment of cerebral adrenal white blood malnutrition (CALD).
July, Lenti-D entered the EMA's Human Medicines Board (CHMP) accelerated review channel, reducing the approval cycle for its EU listing applications from 210 to 150 days.
bluebird plans to file a Lenti-D listing application with the FDA in mid-2021.
previously, Lenti-D Therapeutic CALD was awarded orphan drug status by the FDA and EMA, and in May 2018 he was awarded breakthrough therapy (BTD) by the FDA, and in July 2018 he was granted priority development drug (PRIME) by the EMA.
Lenti-D has also been eligible for the FDA's rare pediatric disease treatment drug, and if approved for the market, Bluebird will receive a priority review voucher worth more than $100 million.
Lenti-D is the removal of self-made hematopoietic stem cells from the patient's body, the use of human ABCD1 gene in vitro lentiviral transductive modification, and then back to the patient.
the expression of ALDP proteins in the body, VLCFA can promote degradation and reduce its savings in the brain.
From the DATA from the FDA's granting of Lenti-D breakthrough therapy and the study data based on Bluebird's application for listing to the EMA, Lenti-D showed better therapeutic potential for delaying disease progression in patients with early CLADA, and did not report transplant anti-host disease, organ rejection, or donor organ failure.
as of January 2020, 32 patients in the ALD-102 study had been treated with Lenti-D, with a medium follow-up time of 30 months (9.1 to 70.7 months) and a stable neurosurgery score of 31 patients.
noted that 23 patients had completed 24 months of follow-up and that 87 per cent (20/23) of patients had survived without major dysfunction (MRD-free).
20 patients continued to enter the long-term follow-up study code-named LTF-304, of which 14 had completed at least 4 years of follow-up and 10 had completed at least 5 years of follow-up.
9 patients who followed for less than 24 months did not show major neurological dysfunction.
Bluebird is also conducting a Phase III study code-named ALD-104 to assess the efficacy and safety of CLADA patients who undergo pretreatment of white anti-an and fluorodalabinume before receiving Lenti-D treatment.
given that Lenti-D is also a better early treatment, early diagnosis of CALD is important because under existing treatment conditions, the clinical outcome of the patient depends on the clinical stage of disease development.
screening of newborns is a key factor in early diagnosis and successful treatment.
once a newborn is diagnosed with ALD, regular MRI scans to indicate changes in white matter are critical to determining whether progression is CALD.
the U.S., neonatal ALD screening was listed as a recommended universal screening in February 2016 and is currently available in 17 states and Washington, D.C., covering 58 percent of U.S. newborns.
outside the U.S., Dutch Health has approved alD for inclusion in its neonatal screening program.
although most EU countries have not yet implemented ALD neonatal screening, they are also trying to move forward in this regard.
original title: Bluebird's breakthrough gene therapy Lenti-D submitted for listing! Improves long-term survival outcomes in patients with fatal rare disease CALD.