Bluebird Bio recently won its second U.S. approval for a gene therapy in as many months, with Skysona, formerly known as eli-cel, crossing the regulatory finish line.
The Food and Drug Administration greenlighted the drug to slow the progression of neurologic dysfunction in boys 4-17 with early, active cerebral adrenoleukodystrophy (CALD), an ultra-rare neurodegenerative disease.
As the first and only FDA-approved treatment for CALD, Bluebird priced the Skysona at a wholesale acquisition price of $3 million. The price tops that of Bluebird’s other gene therapy, the $2.8 million Zynteglo, which was approved last month for the rare blood disorder transfusion dependent beta-thalassemia (TDT).
On a call with analysts Monday morning, CEO Andrew Obenshain said the price reflects the clinical benefit provided by Skysona along with the “urgent need” for treatment options that slow the progression of neurologic dysfunction in CALD, an irreversible and fatal disease.
Despite the drug’s hefty price tag, he said the company is confident that “payers recognize the significance.”
However, unlike with Zynteglo, where the biotech is offering payers an 80% money-back guarantee, “Bluebird doesn’t intend to offer outcome-based pricing for Skysona,” Obenshain said, “because the rarity and complexity make this extremely difficult for Bluebird and for payers.”
Given the progressive nature of CALD, patients’ motivation to seek treatment may also be higher. “With CALD, these boys and their families are urgently seeking treatment options,” said Tom Klima, Bluebird’s chief commercial officer. “It’s a different dynamic than with TDT.”
Skysona should become available later this year, with the first patient apheresis by early 2023, management said. The actual numbers of treated patients will be small given the ultra-rare nature of the condition, the company acknowledged, and the commercial approach is tailored accordingly.
CALD is estimated to affect one in 21,000 newborn males in the U.S., with four in 10 expected to develop the cerebral form of adrenoleukodystrophy, Obenshain noted. This results in an incidence of about 40 boys per year in the U.S. Without treatment, they lose the ability to walk, see and use the toilet. Nearly half die within five years.
The therapy was assessed in two trials – a Phase 2/3 study of 32 subjects (ALD-102) and a Phase 3 study (ALD-104) enrolling 35 – and was shepherded through FDA’s accelerated approval pathway. The proxy endpoint used was the patients’ ability to survive for two years free of six major functional disabilities (MFD). At two years following symptom onset, the treated patients were about 72% more likely to be alive and MFD-free compared to a 43% likelihood for untreated patients.
The biotech is building a comprehensive patient support program, staffed by patient navigators, to support children through all stages of the gene therapy journey, connect them with treatment centers and assist with benefits verification and financial services, Obenshain said.
Despite differences between its two marketed gene therapies, Obenshain said he expects to see some synergies between the two launches. Both therapies are manufactured in the same plant, administered in the same treatment centers, and utilize the biotech’s Lenti-D lentiviral vector to add functional copies of genes.
“It’s incremental resources on top of Zyteglo’s launch, which makes [the Skysona launch] more cost-effective,” Obenshain added.
Both therapies were given a unanimous thumbs-up by an FDA advisory committee in June. Skysona’s uniformly positive vote came as a surprise, given concerns the therapy may cause cancer. Just prior to Friday’s approval, the FDA lifted a clinical hold that it had put on eli-cel last August.
As an accelerated approval, Bluebird agreed to provide confirmatory long-term clinical data. Its long-term follow-up study (LTF-304) is tracking patients treated in clinical trials for 15 years.
The approval also netted Bluebird a second priority review voucher. The firm is in the process of selling both vouchers, worth about $110 million each, to secure non-dilutive financing. That should put the company, which had to lay off 30% of its staff earlier this year in order to stay afloat, in a much stronger cash position.
Bluebird could further solidify its transition to a commercial-stage company, Obenshain noted, as the expected BLA filing of its sickle cell gene therapy, lovo-cel, is still on track to be finalized in early 2023.