EU go-ahead for bluebird bio gene therapy for CALD

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Bluebird’s Lenti-D, or elivaldogene autotemcel, has won approval from the European Commission to treat children with a rare neurodegenerative disease called early cerebral adrenoleukodystrophy (CALD).

The drug is branded as Skysona. The approval is restricted to patients less than 18 years old with an ABCD1 genetic mutation.

The one-time gene therapy is targeted at patients who do not have a matched sibling donor for hematopoietic stem cell (HSC) transplant.

The marketing authorization is supported by efficacy and safety data from the Phase 2/3 Starbeam study (ALD-102), where 90% of patients treated the drug met the primary endpoint of major functional disability (MFD)-free survival at two years follow-up, reported the biotech.

Positive review of Zynteglo

The go-ahead for that gene therapy follows the positive recommendation earlier this month from the EMA in its review of buebird bio’s Zynteglo.

The European Medicines Agency's (EMA) safety committee, Pharmacovigilance Risk Assessment Committee (PRAC), concluded, that there is no evidence betibeglogene autotemcel (beti-cel) gene therapy, licensed as Zynteglo in the EU, causes the blood cancer, acute myeloid leukemia (AML).

Based on the review of all available data, the PRAC said that the benefit-risk balance of medicinal products containing Zynteglo remains favorable.

As a result, Bluebird bio lifted the voluntary suspension on the drug.

Zynteglo is a gene therapy for the blood disorder beta thalassemia. It is a one-time treatment for patients that are 12 years and older who require regular blood transfusions. It was granted conditional marketing authorization in the EU in May 2019.

It uses a viral vector to deliver a working gene into the patient’s blood cells.

The PRAC reviewed two cases of AML in patients treated with an investigational medicine, for LentiGlobin for SCD or bb1111, in a clinical trial for sickle cell disease. Although there have been no reports of AML with Zynteglo, both medicines use the same BB305 lentiviral vector and there was a concern that the vector may be implicated in the development of the cancer.

Bluebird bio decided to temporarily suspend marketing of Zynteglo while the root cause of the safety events reported earlier this year for LentiGlobin for SCD were investigated by the company and assessed by the PRAC.

The EMA review found that the viral vector was unlikely to be the cause. In one of the patients, the viral vector was not present in the cancer cells, and in the other patient it was present at a site (VAMP4) that does not appear to be involved in cancer development.

After examining all the evidence, the PRAC concluded that more plausible explanations for the AML cases included the conditioning treatment the patients received to clear out bone marrow cells and the higher risk of blood cancer in people with sickle cell disease.