- Fresh data on Bluebird Bio's Lenti-D reinforced the encouraging efficacy and safety profile the gene therapy demonstrated in the clinic last year, adding support to regulatory filings planned for 2019.
- Bluebird is testing Lenti-D in boys with a rare metabolic disorder called cerebral adrenoleukodystrophy, or CALD. Last year, early results from the Phase 2/3 STARBEAM trial showed 15 of 17 patients treated with the therapy were alive and free of major functional disabilities (MFDs) after two years. As of April 25, an additional 12 boys were given Lenti-D, none of whom experienced MFDs by a median follow-up of 4.2 months, the company said in a Wednesday statement.
- STARBEAM's primary safety endpoint is the proportion of patients with grade 2 or higher acute graft-versus-host disease (GvHD) or chronic GvHD two years after treatment. None of the 29 patients on Lenti-D have experienced such diseases as of April 25, though there have been three adverse events potentially related to treatment with the therapy, including a grade 3 case of bladder inflammation caused by a virus.
Bluebird has a few busy years ahead. The Massachusetts-based biotech expects to file three therapies, including Lenti-D, for approval by the end of 2019. And by 2022, the aim is to have at least two products on the market.
In a Sept. 5 statement, Bluebird said it reached agreements with the Food and Drug Administration and the European Medicines Agency on regulatory pathways for Lenti-D. Meeting STARBEAM's primary endpoints — MFD-free survival for efficacy, GvHD occurrence for safety — will be key to any approval decisions.
While proponents of gene therapy often tout it as an ultra-effective, one-time remedy for difficult-to-treat diseases, regulators have held some apprehension, particularly when it comes to safety. The FDA halted 27 gene therapy trials in 2003, for instance, after leukemia-like symptoms arose in two children enrolled in a gene therapy study. More recently, investors have been spooked by safety too. Spark Therapeutics lost around $1 billion in its market capitalization earlier this year as data on its hemophilia gene therapy raised some safety concerns.
"Even when there may be uncertainty about some questions, we need to make certain we assure patient safety and adequately characterize the potential risks and demonstrated benefits of these products," FDA Commissioner Scott Gottlieb said in a July statement on new agency guidance for gene therapies.
To the point on safety, Bluebird is running an observational study that looks at outcomes of boys 17 and younger who have CALD and received allogeneic hematopoietic stem cell transplants (HSCTs). The biotech intends to compare data from that study with STARBEAM's safety results.
In that study, 34% of the 41 patients who received allogeneic HSCTs experienced grade 2 or higher acute GvHD or chronic GvHD.
What's more, it's also conducting a long-term safety and efficacy follow-up study for STARBEAM participants treated with Lenti-D.
Bluebird said Lenti-D's safety profile has so far been consistent with certain conditioning therapies used to suppress the immune system before allogeneic HSCTs.
"Data from the Phase 2/3 Starbeam study suggest that Lenti-D, which utilizes a child’s own cells and does not require a matched donor, may be a potential treatment for CALD," Paul Gissen, a consultant in pediatric metabolic diseases at London's Great Ormond Street Hospital and an investigator in the STARBEAM study, said in the Sept. 5 statement.