Betibeglogene autotemcel

The FDA decided that Skysona should not be used in patients with alternative treatment options due to concerns of an increased risk of blood cancer. After telegraphing an investigation in November, the FDA has moved to restrict the use of bluebird bio’s gene therapy Skysona in certain patients.The FDA has updated Skysona’s indication, allowing it to be used only in patients who do not have an available human leukocyte antigen (HLA)-matched donor for stem cell transplant. The one-time therapy is approved to treat cerebral adrenoleukodystrophy (CALD), a rare inherited neurological disorder in which the accumulation of harmful fatty acids in the bloodstream damages the protective myelin sheath around nerve fibers.The FDA decided that Skysona should not be used in patients with alternative treatment options due to concerns of an increased risk of blood cancer.Hematologic malignancies, including life-threatening cases of myelodysplastic syndrome and acute myeloid leukemia, are a known risk factor for Skysona since its approval in 2022 and are reflected in a boxed warning on the drug’s label. The malignant transformation is believed to be likely caused by an insertion of Skysona’s lentiviral vector into the human genome.But an increase in cancer cases triggered an FDA investigation in November 2024, with a regulatory request to update the label this April, according to bluebird. As of July 2025, hematologic malignancies have been diagnosed in 10 (15%) of 67 clinical trial participants, compared with three (4%) incidents at the time of Skysona’s initial approval, according to the FDA. There’s one death related to treatment for the cancer. Existing reports showed no obvious pattern as to when cancer might emerge, as diagnoses ranged from 14 months to 10 years after Skysona administration. However, as the FDA highlighted, some patients developed cancer even before experiencing any therapeutic benefit from the gene therapy.As such, patients are advised to be monitored for blood cancer their entire life. Skysona’s boxed warning asks that patients go through complete blood count checks at least every three months and thorough assessments for evidence of clonal expansion or predominance annually after the first year of treatment.Skysona, with a list price of $3 million per treatment, recorded no sales in the first three months of 2025. Beta-thalassemia therapy Zynteglo saw its sales rise to $26.3 million during the first quarter, compared with $18.6 million a year ago. The sickle cell disease gene therapy Lyfgenia brought in $12.4 million in sales during the period, while Vertex’s rival CRISPR-based treatment Casgevy pulled in $14.2 million.No cases of cancer caused by viral vector insertion have been identified in patients treated with Zynteglo or Lyfgenia, bluebird said in its quarterly report filed in May. As commercial progress of the three gene therapies fails to impress and a debt payment nears its due date, bluebird bio recently sold itself to Carlyle and SK Capital Partners for $49 million, or $5 per share, following some investor resistance to a previous lower offer price.The acquisition also offers an alternative payment method, which includes a $3-per-share payment upfront and $6.84-apiece contingence value rights, which are payable if bluebird’s three marketed products reach $600 million over a 12-month period by the end of 2027.

The FDA has ordered label changes for bluebird bio's Skysona (elivaldogene autotemcel), tightening its use to a narrower patient population after a review uncovered a marked increase in blood cancer cases among clinical trial participants. The move comes shortly after bluebird, beset by weak sales for its portfolio of gene therapies and mounting financial strain, was taken private in June by Carlyle and SK Capital.Approved in 2022 at a US list price of $3 million as a one-time treatment for boys with cerebral adrenoleukodystrophy (CALD), Skysona will now be indicated only for patients without a suitable human leukocyte antigen (HLA)-matched allogeneic stem-cell donor.The lentiviral vector-based therapy's US label already carried a boxed warning about haematologic malignancy, but the FDA launched a formal review last November after an NEJM report described seven children developing cancers – six cases of myelodysplastic syndrome (MDS) and one of acute myeloid leukemia (AML) – within 14 to 92 months post-treatment.At approval, MDS had been reported in three of 67 trial participants (4%), according to an FDA statement on Thursday. Updated data show malignancies in 10 of 67 patients (15%) as of July, more than tripling the previously reported incidence. So far, there has been one death related to treatment for malignancy, while another patient experienced a recurrence of MDS following initial therapy, necessitating re-treatment."Importantly, some patients developed malignancy before Skysona had time to potentially provide therapeutic benefit for their CALD," the FDA noted. Diagnoses of haematologic malignancy have occurred anywhere from 14 months to a decade after Skysona administration, the agency said.The FDA also urged close, long-term monitoring for Skysona recipients, recommending complete blood counts every three months, targeted checks for clonal expansion or predominance at least twice in the first year and annually thereafter, as well as bone marrow evaluations if clinically indicated.For bluebird, the safety decision compounds commercial challenges for Skysona, and its other two high-priced gene therapies – Zynteglo (betibeglogene autotemcel) for beta thalassemia and Lyfgenia (lovotibeglogene autotemcel) for sickle cell disease – that have struggled to meet revenue expectations despite high price tags.In 2024, bluebird initiated treatment for 70 patients across its gene therapy portfolio – 43 with Zynteglo, 21 with Lyfgenia, and six with Skysona. By March 25 of this year, the company had begun therapy for 14 Zynteglo and 11 Lyfgenia patients, with no new Skysona starts recorded.