Bluebird's breakthrough gene therapy Lenti-D is on the market! Improves long-term survival outcomes in patients with fatal rare disease CALD.

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 among young boys, affecting approximately 21,000 male newborns worldwide.
ALD is caused by mutations in the ABCD1 gene that cause changes or functional deficiencies in the structure of the adrenal white matter malnutrition protein (ALDP) encoded by the ABCD1 gene, which prevents the very 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 lead to nervous system demyelination and adrenal cortical function decline and other pathological changes.
adrenal brain white dystrophy (cerebral adrenoleukodystrophy, CALD) is one of the most severe 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, cortique blindness (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 has no special effect therapy, allo-HSCT is the current clinical alD standard treatment, can correct VLCFA metabolic disorders, improve clinical symptoms, improve long-term survival rate.
But allo-HSCT requires early treatment to be effective, and is limited by the patient's bone marrow matching donor is difficult to obtain, in addition to the immune rejection response, transplant-related death, transplant anti-host disease risk 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 its gene therapy, Lenti-D. , Eli-cel) is a listing application 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 was awarded breakthrough therapy (BTD) by the FDA, and in July 2018 was granted priority development drug (PRIME) status by the EMA.
Lenti-D has also been eligible for 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.
-D is the removal of self-hematopoietic stem cells from the patient's body, the in vitro use of human ABCD1 gene 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 to the EMA for listing, Lenti-D showed good therapeutic potential for early CLADA patients to delay disease progression, and no transplant anti-host disease, organ rejection or donor organ failure was reported.
as of January 2020, 32 patients in the ALD-102 study were treated with Lenti-D, with a medium follow-up time of 30 months (9.1 to 70.7 months) and a stable neurologic function score of 31 patients.
noted that 23 patients had completed 24 months of follow-up and that 87 per cent (20/23) 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 disorders.
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 United States, 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 newborns in the United States.
outside the U.S., Dutch Health has approved the inclusion of ALD 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.
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