Bluebird bio, reeling from Zynteglo safety scare, snags EU nod for new gene therapy against rare neurodegenerative disease

Things are looking up for bluebird bio. Just as the company is resuming European marketing of blood disorder drug Zynteglo after a safety scare, it has won local clearance for another one-time gene therapy.

Bluebird’s Lenti-D, or elivaldogene autotemcel, has secured approval from the European Commission to treat children with a rare neurodegenerative disease called early cerebral adrenoleukodystrophy (CALD), the biotech said Wednesday. The drug is now branded under the name Skysona.

The go-ahead is restricted to patients less than 18 years old with an ABCD1 genetic mutation. The one-time gene therapy is allowed only for patients who don’t have a matched sibling donor for hematopoietic stem cell (HSC) transplant, who bluebird estimates make up about 80% of CALD cases.

Bluebird said it’s on track to file the drug with the U.S. FDA mid-2021. Drug regulators in the U.K. are already reviewing its application. The company will share Skysona pricing and EU launch plans at a later date, a bluebird spokesperson said.

Because of the disease’s rare nature, analysts at Jefferies recently projected only $74 million in peak sales for Skysona.

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ALD is caused by mutations in the ABCD1 gene, leading to toxic buildup of fatty acids in the adrenal gland, the brain and spinal cord. CALD, the most severe form of ALD, involves damage to the protective myelin sheath around nerve fibers. ALD primarily affects males, with an estimated diagnosis rate of one in 21,000 male newborns, and CALD constitutes about 40% of all ALD cases.

Skysona uses a lentiviral vector to incorporate functional copies of the ABCD1 gene into a patient’s own HSCs. The goal is that the new gene will produce the ALD protein, which helps break down the fatty acids and by doing so, preserves neurological function.

Zynteglo also uses a lentiviral vector, though different from the Lenti-D carrier. Zynteglo is approved to treat beta-thalassemia in the EU and is also being tested for sickle cell disease under the code name LentiGlobin.

After reports of blood cancer emerged earlier this year from LentiGlobin’s sickle cell disease clinical trial, concerns were that the viral vector was to blame. But an investigation later exonerated the vector, and bluebird has since resumed the drug’s clinical trials with permissions from regulators and has relaunched Zynteglo in EU.

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In 2019, Bluebird set Zynteglo's list price at about $1.8 million for beta thalassemia. For the one-time treatment, the company has offered an outcomes-based payment model that only requires payment if the therapy delivers on its promise over years. But reimbursement talks didn’t go as planned with regulators in Germany—the drug’s first launch country—and bluebird in April said it would withdraw Zynteglo from the country.

As for Skysona's clinical development, the gene therapy showed in two trials that it could help most patients live free of major functional disabilities without the need for a stem cell transplant or rescue cell administration in two years. Among 27 patients who rolled over into another long-term follow-up trial, 26 remained alive and major disability-free through their last follow-up, including 14 patients who reached at least their fifth year of follow-up.