PharmaShots Interview: bluebird bio's Rich Colvin Shares Insights on the Skysona to Treat Early Cerebral Adrenoleukodystrophy

In an interview with PharmaShots, Rich Colvin, M.D., Ph.D., Interim Chief Medical Officer at bluebird bio shares his views on the Skysona and its working on CALD patients.

Shots:

If granted marketing authorization, Skysona would be the first approved one-time gene therapy for CALD which is a rare neurogenerative disease with typically childhood onset
The CHMP opinion is supported by data from the Starbeam trial, which showed that Skysona was safe, efficacious, and durable in treating CALD in most patients
The EMA has previously accepted Skysona into its Priorities Medicines scheme (PRIME) and granted it Orphan Medicinal Product designation, recognizing the importance of a new treatment option for the severe unmet need in the patient population

Tuba: Can you share information about the epidemiology, prevalence, and incidence of ALD and CALD?

Rich Colvin: Adrenoleukodystrophy (ALD) is a rare, X-linked metabolic disorder that primarily affects males; worldwide, an estimated one in 21,000 male newborns are diagnosed with ALD. The disorder is caused by mutations in the ABCD1 gene that affect the production of adrenoleukodystrophy protein (ALDP) and subsequently cause toxic accumulation of very-long-chain fatty acids (VLCFAs), primarily in the adrenal gland and white matter of the brain and spinal cord. Approximately 40% of boys with ALD will develop CALD, the most severe form of ALD. CALD is a progressive and irreversible neurodegenerative disease that involves the breakdown of myelin, the protective sheath of the nerve cells in the brain responsible for thinking and muscle control. The onset of symptoms of CALD typically occurs in childhood (median age 7).

Tuba: What is SKYSONA and how does it work?

Rich Colvin: SKYSONA is a one-time investigational gene therapy that uses ex vivo transduction with the Lenti-D lentiviral vector (LVV) to add functional copies of the ABCD1 gene into a patient's own hematopoietic (blood) stem cells (HSCs). The addition of the functional ABCD1 gene allows patients to produce the ALD protein, which is thought to facilitate the breakdown of VLCFAs. The goal of treatment with SKYSONA is to stabilize the progression of CALD and, consequently, preserve as much neurological function as possible, including the preservation of motor function and communication ability. Importantly, with SKYSONA, there is no need for donor HSCs from another person.

Tuba: Can we discuss the trial design and key features of the Starbeam (Ph2/3) Study?

Rich Colvin: The ongoing, pivotal Phase 2/3 Starbeam study (ALD-102) treated 32 patients with a median follow-up time of 38.6 months (13.4 82.7 months), as of the last data set reported at the EBMT 2021 virtual congress. Of the 32 patients who have received eli-cel in ALD-102, 27 have completed the study and enrolled in a long-term follow-up study (LTF-304). Two additional patients continue to be followed in ALD-102 and have not reached 24 months post-treatment.

The primary efficacy endpoint in the study is the proportion of patients who are alive and free of MFDs at Month 24. Of those patients who have reached Month 24, 90% (n=27/30) have met the primary endpoint and continue to be alive and MFD-free at two years of follow-up. There is no evidence of MFDs through nearly seven years (up to 82.7 months) of follow-up in the 27 patients who completed ALD-102. Fourteen patients in LTF-304 have reached at least their Year 5 follow-up visit, including seven patients who have reached at least their Year 6 follow-up visit. The two patients from ALD-102 that have not reached Month 24 have also shown no evidence of MFDs.

As previously reported, two patients withdrew from the study at the investigator's discretion, and one experienced rapid disease progression early on in the study, resulting in MFDs and subsequent death.

In ALD-102, 26/28 evaluable patients maintained a neurologic function score (NFS) less than or equal to 1 through Month 24, and 24 of those patients had no change in their NFS, which showed maintenance of neurological function in the majority of patients. All patients who completed ALD-102 enrolled for long-term follow-up in the LTF-304 study. The median duration of follow-up was 38.59 months (min.: 13.4; max.: 82.7).

The treatment regimen, comprising mobilization/apheresis, conditioning, and SKYSONA infusion, had a safety/tolerability profile primarily reflective of the known effects of mobilization/apheresis and conditioning.

See more information here: https://investor.bluebirdbio.com/news-releases/news-release-details/bluebird-bio-presents-long-term-data-elivaldogene-autotemcel-eli

Tuba: When can we expect the availability of SKYSONA in the market as it will be the first approved one-time gene therapy for CALD in pediatric patients (<18yrs)?

Rich Colvin: A final decision by the EC for SKYSONA is anticipated in mid-2021. Due to the highly coordinated and specialized nature of administering gene therapy in rare diseases, the company is partnering with institutions in Europe that have expertise in stem cell transplant as well as in treating patients with ALD to create qualified treatment centers that will administer SKYSONA. In addition, the company has submitted SKYSONA for a pan-European clinical assessment to facilitate access through cross-border healthcare pathways for patients who do not have local country access.

Tuba: When can we expect bluebird bio to submit SKYSONA for approval for CALD in the U.S.?

Rich Colvin: bluebird bio is currently on track to submit the Biologics License Application (BLA) in the U.S. by mid-2021.

Tuba: What are the digital and other initiatives taken by Bluebird bio to educate HCPs and patients?

Rich Colvin: bluebird bio worked with ALD families to develop this informational site, which includes support and resources for building a care team and connecting with the ALD community. This website is for residents of the United States only: https://www.navigatingald.com/

Additionally, the newborn screening for adrenoleukodystrophy advocacy tool kit is an empowering and educational resource created by bluebird bio in collaboration with patient advocacy organizations and advocacy leaders to raise awareness of adrenoleukodystrophy (ALD) and the life-saving opportunity newborn screening (NBS) can provide: https://www.bluebirdbio.com/patients-and-advocacy/newborn-screening-toolkit-for-ALD

Image Source: Adrenoleukodystrophy News

About Rich Colvin:

Rich Colvin serves as Vice President, Head Severe Genetic Diseases Clinical Research and Development. He joined bluebird bio in 2018 after nine years with the Novartis Institutes for BioMedical Research (NIBR). Colvin has also spent 14 years as a physician at Massachusetts General Hospital in the MGH Chelsea Healthcare Center.