Bluebird Bio’s Rare Disease Gene Therapies Recommended for FDA Approval

Last week, the FDA Cellular, Tissue, and Gene Therapies Advisory Committee (CTGTAC) voted 15 – 0, concluding that the benefits of bluebird bio’s gene therapy to treat cerebral adrenoleukodystrophy (CALD) outweighed its risks. One day after that decision, the same panel voted 13 – 0 in favor of bluebird’s beta-thalassemia gene therapy. The company is now waiting for final FDA approval for both drugs that will likely make or break their business.

CALD is a rare neurodegenerative disease usually striking within the first decade of life and often resulting in death within a few years of diagnosis. Support for elivaldogene autotemcel (eli-cel) in the treatment of CALD was based on Phase 2/3 Starbeam clinical trial results that found patients treated with eli-cel were more likely to achieve survival than those not treated with the drug.

The trial had previously been put on hold after a patient treated with the gene therapy suffered a serious adverse reaction resulting in myelodysplastic syndrome. Two additional reactions of this type were recorded after the trial was resumed. 

Bluebird’s treatment for beta-thalassemia — a rare blood disease — was recommended based on Northstar, a three-phase clinical trial. Beti-cel was shown to eliminate the long-term need for blood transfusions in 64% of Phase 1 patients and 90% of Phase 3 patients. Severe adverse events recorded in the trial included gonadotropic insufficiency, ectopic pregnancy, gall bladder wall thickening/polyp, bacteremia, neutropenia, and major depression.

The FDA has been known to approve medications despite serious adverse reactions. Occasionally, these approvals are limited in scope to specific groups of patients.

As it stands, bluebird desperately needs FDA approval for both drugs after it discontinued its program for a sickle cell treatment in 2021 and backed out of the European pharmaceutical market entirely. The decision to end clinical trials of LentiGlobin for treating sickle cell disease came after a patient developed myelodysplastic syndrome. Bluebird’s then CEO proceeded to leave the company soon afterward.

Since its sickle cell treatment failed and its former CEO disembarked, bluebird doubled down on its one-time gene therapies. It progressed in the clinical trial pipeline with its eight genetic therapies, but the company will face irreconcilable loss if its eli-cel and beti-cel treatments do not reach the market.

Both of bluebird’s gene therapies currently under evaluation are eligible for priority review vouchers. The FDA may decide on approval as soon as August for the firm’s beti-cel therapy and September for its eli-cel treatment.