As bluebird bio (“bluebird”) waited on FDA feedback regarding the manufacturing process for lovotibeglogene autotemcel (lovo-cel) genetherapy, the company disclosed that it would most likely miss its Q1 submission deadline at the end of March 2023. While this did happen, it isn’t all bad news for bluebird. Despite the brief delay, the company shared on April 24, 2023, that they had submitted a Biologics License Application (BLA) to the FDA for lovo-cel gene therapy. This product is being developed as a treatment for sickle cell disease (SCD) in people aged 12+ who have a history of vaso-occlusive events (VOEs). VOEs, as explained by Change for SCD, are:
a group of acute complications that are associated with SCD and include vaso-occlusive pain crises, acute chest syndrome (ACS), stroke, and splenic sequestration.
VOEs can be difficult to deal with and can have a detrimental effect on patients, families, and their daily lives. Finding ways to manage, reduce, or even prevent VOEs could significantly improve how someone feels both physically and mentally.
What is Lovo-Cel Therapy – and Why Do They Submit a BLA?
This investigational lentiviral gene therapy imbues a functional, but modified, βA-T87Q-globin gene to hematopoietic stem cells from the patient being treated. Providing functional βA-T87Q-globin prompts red blood cells to create anti-sickling hemoglobin (HbAT87Q). Ultimately, the goal of lovo-cel gene therapy is to prevent the formation of sickle-shaped red blood cells and red blood cell death. This therapy has received Rare Pediatric Disease, Regenerative Medicine Advanced Therapy, Orphan Drug, and Fast Track designations.
Studies performed on lovo-cel gene therapy show its promise. Included in the BLA is efficacy data from 38 participants between the Phase 1/2 HGB-206 study and Phase 3 HGB-210 study. The company also included safety data from 50 patients treated throughout the entire clinical development program. Lovo-cel gene therapy was shown to reduce pain crises and improve red blood cell health and function in those treated. Side effects did occur, such as low blood pressure, anemia, and flushed skin.
bluebird submitted a Biologics License Application because, if approved, the company can introduce lovo-cel gene therapy for use and sale. Learn more about the BLA process here.
As part of their submission, bluebird asked the FDA for Priority Review of their BLA. The FDA may choose whether or not to grant this based on the information that they have been given. If the FDA chooses to grant Priority Review, the FDA must provide bluebird with a decision within 6 months after filing. This is 4 months shorter than the standard review process for BLAs.
The Facts of Sickle Cell Disease (SCD)
Sickle cell disease refers to a group of inherited red blood cell disorders. SCD develops when the gene responsible for hemoglobin, which carries oxygen through the body, mutates. This causes hemoglobin S to become rigid, sticky, and sickle-shaped. As these sickle-shaped blood cells move through the body, they can block capillaries, restrict blood flow, and cause a number of painful symptoms. Sickle cell anemia is considered to be the most common and most severe form of SCD. In many cases, SCD is diagnosed at or near birth; it is included on the newborn screening panel. People of African American descent are at a higher risk of developing SCD. Symptoms may be constant for adults and only experienced during pain crisis for children, but this is not always the case. These symptoms, which may appear in the first few months of life, can include:
- Fatigue
- Anemia (low red blood cell count)
- Splenic sequestration
- Painful swelling of the hands and feet
- Fussiness (in infants)
- Jaundice (yellowing of the skin, eyes, and mucous membranes)
- Pain crisis
- Organ damage
- Stroke
Right now, there are no cures for sickle cell disease.
