FDA restricts use of bluebird's Skysona gene therapy

The FDA has added a warning label to bluebird bio's Skysona, after launching an investigation into cases of blood cancer in patients treated with the ex vivo gene therapy last November.

Skysona (elivaldogene autotemcel) was approved by the US regulator in 2022, becoming the therapy shown to slow the progression of neurologic dysfunction in boys with the rare neurological disorder cerebral adrenoleukodystrophy (CALD).

In a statement, the US regulator said its review had revealed haematological malignancies seem to occur in around 15% of clinical trial participants, roughly three times the rate recorded when Skysona was first approved. One death "related to treatment for malignancy has occurred," it added.

Haematological cancers are a recognised potential side effect with Skysona and were already mentioned in a boxed warning on the gene therapy's approved labelling. The new label restricts use of the therapy to patients who don't have a suitable donor for a haematopoietic stem cell transplant (HSCT), previously the only therapy for CALD.

The FDA said it has received additional reports, including life-threatening cases of myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML), that seem to occur between 14 months and 10 years after treatment with Skysona.

That involves using a lentiviral vector to replace the mutated ABCD1 gene in CALD patients with a functional copy in haematopoietic stem cells harvested from the patient. The modified cells are reinfused and can produce a functional version of the ALD protein that is lacking in CALD. However, it is thought that the cancer genes can sometimes be activated when the lentivirus carrying the genetic payload integrates into the patient's DNA.

"Skysona should only be used in CALD patients without suitable alternative treatment options, given the increased risk of haematologic malignancy," according to the regulator.

For bluebird, the restriction will cut into the revenue potential for $3-million product Skysona, one of three gene therapies sold by the loss-making company, which has struggled to build a commercially viable business.

Earlier this year, the formerly Nasdaq-listed company was bought by investment groups Carlyle and SK Capital Partners for just $29 million, and is now operating as a private company under the leadership of new chief executive David Meek.

It also sells Zynteglo (betibeglogene autotemcel) for beta thalassaemia and Lyfgenia (lovotibeglogene autotemcel) for sickle cell disease, and remains one of the few standalone commercial gene therapy companies, reflecting the challenges in winning the reimbursement coverage for the expensive, one-shot medicines needed to build a sustainable business.

In a Securities & Exchange Commission (SEC) filing published ahead of the takeover, bluebird revealed that its gene therapies were used to treat 70 patients last year, including 43 for Zynteglo, 21 for Lyfgenia, and six for Skysona. Meanwhile, between the start of the year and the end of March, there were 14 patient starts for Zynteglo and 11 for Lyfgenia, with none recorded for Skysona.

Photo by Markus Spiske on Unsplash