Sickle cell disease (“SCD”) is an inherited blood cell disorder that causes red blood cells (“RBCs”) to be sickle shaped, which in turn affects how they carry oxygen throughout the body. This can easily block blood flow and cause a variety of complications varying in severity, such as: severe pain crises (e.g., vaso-occlusive crises), infections, organ damage, strokes, and painful swelling throughout the body. SCD disproportionally affects people of African descent. One in 13 African American children are born with the Sickle Cell Trait and 1 in 365 are born with actual sickle cell.[1] The average life expectancy for people living with this disease is about 20-years shorter than the national average of 79 years old.[2] To combat this crippling disease, Pfizer developed a promising drug named Oxbryta (Voxelotor).
What was so promising about Oxbryta (Voxelotor)?
Oxbryta was the very first of its kind: a sickle cell drug that targets the root cause of the disease on a cellular level. Until Voxelotor was developed, existing treatments focused on prevention of painful episodes, symptom management and reducing the need for blood transfusions.
How does it work?
Oxbryta prevents Hemoglobin S polymerization—the process which prevents RBCs from becoming sickle-shaped.
In November 2019, Oxbryta was initially approved for clinical trials in patients 12 years or older. In December 2021, that approval was expanded to include children ages 4 and up.[3] This occurred during Phase 3 of drug development where the goal is to establish safety, efficacy for the indication, and prove the drug can transition into the open market. On September 25, 2024, Pfizer voluntarily withdrew Oxbryta due to the benefits no longer outweighing the risks. Oxbryta was recalled for dangerous adverse events; specifically, vaso-occlusive crises, fatal events, and in 16 cases, death.[4] Vaso-occlusive crises are not only the most common complication from sickle cell disease, but they are also responsible for the majority of hospitalizations. During the crises, the RBCs get stuck in small blood vessels, restricting blood flow throughout the body and cause significant pain and inflammation. If left untreated, or not treated promptly, these crises can lead to organ damage that may also be irreversible.
What can we take away from this?
When a drug introduces new pharmacology, especially by targeting a disease on a mechanistic level, this impact can change the course of how providers manage the disease entirely! The truth of the matter is funding research for pharmaceuticals is essential to moving healthcare forward. In 2021, it was estimated by the World Health Organization (WHO) that approximately 7.74 million people worldwide are living with sickle cell disease, and it is the 12th leading cause of death in those under 5 years old.[5] There are also several barriers to treatment as this disease can be multifaceted and manifest differently in patients. Imagine the impact of having a drug on the market that can actually treat the disease itself, and save countless people from going through “trial and error” with their medication regimen.
[1] https://www.cdc.gov/sickle-cell/data/index.html
[2] https://www.cdc.gov/sickle-cell/data/index.html
[3] https://sicklecellanemianews.com/news/fda-approves-oxbryta-1st-treatment-targeting-root-cause-sickle-cell/
[4] https://sicklecellanemianews.com/oxbryta-voxelotor-gbt440-sickle-cell-anemia/
[5] https://www.who.int/news-room/fact-sheets/detail/sickle-cell-disease
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