The title of the world’s most expensive treatment has changed hands within one company in a month.
On the heels of an FDA go-ahead for gene therapy Zynteglo, bluebird bio has won an FDA accelerated approval for Skysona, or eli-cel, for the rare neurological disorder cerebral adrenoleukodystrophy (CALD), the company said Friday. The company is charging $3 million per treatment with Skysona, higher than Zynteglo’s $2.8 million, making it the priciest therapy in the world.
Unlike Zynteglo, a beta thalassemia therapy, bluebird won’t offer an outcomes-based payment for Skysona because the rarity and complexity of CALD makes such an arrangement “extremely challenging to implement for both bluebird and payers,” bluebird CEO Andrew Obenshain told investors during a conference call Monday.
The price tag reflects “the clinical benefit [Skysona] provides as an urgently needed treatment option to slow the progression of neurologic dysfunction in children impacted by progressive, irreversible and fatal rare disease,” Obenshain added.
Skysona is bluebird’s second gene therapy after Zynteglo in the U.S. Previously, the biotech had to pull both products in Europe and folded commercial activities in the region after failing to reach reimbursement agreements with local governments.
Because of their potential to treat life-threatening diseases with a one-dose treatment, gene therapies are very costly. Before Zynteglo and Skysona, the title of the world’s most expensive drug belonged to Novartis’ spinal muscular atrophy gene therapy Zolgensma, which carries a $2.1 million list price.
CALD is marked by neurologic decline, which can lead to complete loss of voluntary movement. Without treatment, about half of patients—primarily boys—die within five years of symptom onset. Skysona is allowed to treat boys 4 to 17 years of age with early, active CALD.
By bluebird’s estimate, ALD affect about 1 in 21,000 newborn males in the U.S., and 4 in 10 are expected to develop the cerebral form. This translates into, altogether, about 40 cases per year in the U.S.
The FDA handed out the accelerated approval based on data from two small clinical trials. The drug was found to be better than natural history data at preventing the emergence of functional disabilities or death after two years.
To confirm Skysona’s efficacy for a potential full approval, bluebird has rolled over the 67 patients treated with the gene therapy in the two clinical trials into a longer follow-up trial to continue monitoring safety and efficacy data through 15 years, bluebird Chief Medical Officer Rich Colvin, M.D., Ph.D., said on the call. Additional data from commercially treated patients will also be counted.
Right before granting the approval, the FDA also lifted a clinical hold that it previously issued in August 2021. The hold was in place after a patient who got Skysona developed myelodysplastic syndrome (MDS), a type of blood cancer. Altogether, three patients in Skysona’s clinical program showed MDS, which is believed to be caused by the Lenti-D viral vector that bluebird uses to deliver a functional ABCD1 gene into the human genome. Skysona comes with a boxed warning for hematologic malignancy.
“We are confident that the risks of Skysona will be weighed carefully with the risks of other treatment approaches and the CALD itself, as families and clinicians make these complex and deeply personal treatment decisions,” Obenshain said.
Bluebird plans to make Skysona commercially available by the end of 2022 at designated treatment centers, initially only at Boston Children’s Hospital and Children’s Hospital of Philadelphia.
Besides the previous clinical hold on Skysona, the FDA also has an ongoing partial clinical hold on Zynteglo’s sister med, lovo-cel, in sickle cell disease. The agency put the temporary suspension in place in late 2021 following one case of persistent, non-transfusion-dependent anemia. Bluebird is still “in correspondence with the FDA,” and the company has no estimate on when the hold might be resolved, Obenshain said.
The two back-to-back approvals give bluebird two priority review vouchers, which the company plans to sell for around $100 million each to keep operations running. The European commercial setback and the multiple clinical holds led to a restructuring that bluebird launched in April.
Bluebird expects the overhaul will reduce its annual cash burn to $240 million to $245 million in 2023, Chief Strategy and Financial Officer Jason Cole said on the call. The company believes it has “sufficient resources to successfully commercialize Zynteglo as well as Skysona and to file the lovo-cell [biologics application] on time in the first quarter of 2023,” Cole said.