“said lead author Hanny Al-Samkari, MD, a hematologist and clinical investigator at MGH and an assistant professor of Medicine at Harvard Medical School.
“Furthermore, most patients develop other potentially serious complications, such as iron retention in the liver and/or heart (which can cause cancer or death), osteoporosis, gallbladder disease, blood clots, and other complications. Other problems. “
Pyruvate kinase deficiency is characterized by mutations in the PKLR gene that encodes the enzyme pyruvate kinase in red blood cells. This enzyme is important for maintaining the energy levels of red blood cells and, therefore, their normal lifespan.
Mitapivat is able to activate and stabilize the mutated pyruvate kinase expressed in the patient’s red blood cells, thereby restoring enzyme activity.
“It is a ‘disease-modifying’ therapy because it targets the underlying problem to improve or eliminate anemia and has the potential to prevent or reverse many of the other complications associated with pyruvate kinase deficiency.Al-Samkari said.
“It is the first disease-modifying drug for pyruvate kinase deficiency, which has so far been treated only with supportive measures such as blood transfusions or removal of the patient’s spleen.. “
In the ACTIVATE trial designed and conducted by Al-Samkari and his colleagues, 80 patients were randomized to receive mitapivat (5 mg twice daily, potentially increased to 20 or 50 mg twice daily). days) or placebo for 24 weeks.
The primary endpoint was sustained hemoglobin response at two or more scheduled assessments at weeks 16, 20, and 24.
16 of the 40 patients (40%) who received mitapivat had a hemoglobin response, compared with none who received placebo.
Patients who received mitapivat also responded better than patients who received placebo for secondary endpoints, including other markers of red blood cell health.
Mitapivat-treated patients also had a significant improvement in quality of life compared with placebo-treated patients as measured by disease-specific instruments.
The most common adverse events were nausea (in 18% of patients in the mitapivat group and 23% of the patients in the placebo group) and headache (in 15% of the patients in the mitapivat group and 33% of the patients in the sham group). pharmacy).
“The opportunity to develop a disease-modifying therapy for a disease like pyruvate kinase deficiency could not only help patients with the condition, but also offer hope to patients with other similar disorders.Al-Samkari said.
“Since energy is everything to red blood cells, this drug can help patients with more common ischemic conditions such as sickle cell disease and thalassemia. We are looking at this right now in other clinical trials and early studies are very promising. “