ICYMI: Exa-cel for Beta Thalassemia, Sickle Cell Disease Accepted for Priority Review by Health Canada

On December 13, 1996, Health Canada issued a policy statement called Priority Review of Drug Submissions which:

provided for the “fast-tracking” of eligible New Drug Submissions (NDS) and Supplemental New Drug Submissions (SNDS) intended for the treatment, prevention or diagnosis of serious, life-threatening or severely debilitating diseases or conditions.

Though the processes have shifted over time, Priority Review is now granted to submitted NDS and SNDS applications and reduced the review timeline of these applications from 300 to 180 days. An article in The Malaysian Reserve shared that, in April 2024, Health Canada accepted an NDS for Priority Review. This NDS, submitted by global biotechnology company Vertex Pharmaceuticals (“Vertex”), centers around exagamglogene autotemcel (exa-cel) for individuals ages 12+ with either transfusion-dependent beta thalassemia or sickle cell disease with recurrent vaso-occlusive crises. Vaso-occlusive crises occur when sickled red blood cells block blood flow, depriving tissue of oxygen and causing significant pain.

What is Transfusion-Dependent Beta Thalassemia?

Beta thalassemia is an inherited blood disorder caused by HBB gene mutations. These mutations lead to lower levels of hemoglobin (an iron-rich protein in red blood cells that carries oxygen throughout the body). There are three forms of beta thalassemia: minor, intermediate, and major. People with the minor form often have (as you might expect) minor symptoms, and some may experience no symptoms at all. However, people with major beta thalassemia typically require regular blood transfusions and iron chelation therapy, as well as lifelong care. This can lead to transfusion-dependent beta thalassemia, where individuals do not produce enough hemoglobin and must have blood transfusions to maintain levels of hemoglobin in the body. Symptoms of transfusion-dependent beta thalassemia can include:

  • Anemia (low red blood cell count)
  • Fatigue and general weakness
  • Headaches
  • Failure to thrive in infants
  • Jaundice (yellowing of the skin, eyes, and mucous membranes)
  • Dizziness
  • Feeding difficulties
  • Diarrhea
  • Irritability
  • Thinning and brittle bones
  • Shortness of breath
  • Extremely pale skin
  • Hypersplenism (an overactive spleen)
  • An enlarged spleen and liver (hepatosplenomegaly)
  • Distinctive facial features such as an abnormally prominent forehead, full cheekbones, and upper jaw overgrowth

Without treatment, people with this disorder can experience severe health complications and reduced life expectancy. Iron chelation therapy is needed alongside transfusions as frequent transfusions lead to iron overload, which can cause organ damage.

NDS Support

A Vertex news release on the approval of exa-cel in the US explains that exa-cel is a gene therapy which uses someone’s own hematopoietic stem and progenitor cells. This contributes to heightened production of fetal hemoglobin in red blood cells, allowing for increased blood oxygenation.

Prior study data has shown that exa-cel reduces or eliminates the occurrence of vaso-occlusive crises in sickle cell disease and reduces or eliminates the burden of transfusion requirements in transfusion-dependent beta thalassemia.

To support the New Drug Submission in Canada, Vertex submitted data on exa-cel from the ongoing Phase 3 CLIMB-111 and CLIMB-121 studies, alongside data from the CLIMB-131 study. The first two studies are evaluating how safe and effective a singular exa-cel dose is in patients between ages 12-35, with the latter study evaluating how safe and effective exa-cel is in patients who have previously been treated with this therapy.

Jessica Lynn

Jessica Lynn

Jessica Lynn has an educational background in writing and marketing. She firmly believes in the power of writing in amplifying voices, and looks forward to doing so for the rare disease community.

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