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Why do some FDA-approved drugs get a Black Box Warning (BBW)?

Last Friday, the U.S. Food and Drug Administration (FDA) approved two gene therapies for sickle cell disease. This marks a significant milestone as one of these therapies is the first treatment in the United States that utilizes the CRISPR gene editing technology. Sickle cell disease is an inherited blood disorder where the body produces abnormal, sickle-shaped hemoglobin, causing red blood cells to have difficulty carrying oxygen to the body's tissues.

Lyfgenia and Casgevy are two different approaches. Lyfgenia delivers modified genes into the body by disabled viruses, while Casgevy uses molecular "scissors" to remove faulty gene parts and either disable or replace them with normal DNA strands.

Even though both drugs were approved on the same day, Lyfgenia was given a Black Box Warning (BBW). A BBW is the highest warning that can be issued for a drug by the FDA, indicating a severe risk to patient health linked to the drug. This is highlighted in a black box on the medication package insert.

Why approve the drug if it comes with a big warning?

There are currently 400 drugs approved with BBW’s. It is a necessary precaution. These medications are often administered to patients who are critically ill as the final line of treatment when others haven’t worked. However, the drug is still approved because the effectiveness of these drugs has proven to be greater than the associated risks. Still, a BBW is provided because patients must be fully informed about the potential risks and make informed decisions regarding the medications they will be taking.

The UK equivalent is the Medicines and Healthcare products Regulatory Agency’s (MHRA) Black Triangle warning.

  • Leo, L. and Satija, B. (2023) 'US FDA approves two gene therapies for sickle cell disease,' Reuters, 8 December.
  • Box warning - statpearls - NCBI bookshelf. Available at: (Accessed: 11 December 2023). 
  • Medicines and Healthcare products Regulatory Agency (no date) The Black Triangle Scheme (▼ or ▼*).