The outcomes of the randomised placebo-controlled ACTIVATE trial were released in the New England Journal of Medicine and were carried out by a global team that included researchers from Massachusetts General Hospital.
The majority of people who have pyruvate kinase deficiency experience potentially fatal complications such iron overload in the liver and/or heart, osteoporosis, gallbladder disease, blood clots, and other problems as a result of their lifelong anaemia.
The results of a phase 3 clinical trial, which showed that the oral medication “mitapivat” is safe and effective for treating adults with pyruvate kinase deficiency, a genetic disorder that results in hemolytic anaemia or the destruction of red blood cells, were recently approved by the U.S. FDA.
80 patients were randomised to receive either mitapivat (5 mg twice day, with a potential increase to 20 or 50 mg twice daily) or a placebo for 24 weeks in the ACTIVATE experiment created and carried out by Al-Samkari and his colleagues.
A sustained haemoglobin response (a marker of red blood cell levels) at two or more of the scheduled evaluations at weeks 16, 20, and 24 served as the primary outcome. In comparison to none of the patients who received placebo, 16 of the 40 patients (or 40%) who took mitapivat experienced an increase in haemoglobin(Hb). Patients who got mitapivat also responded better to secondary objectives, such as other indicators of red blood cell health, than patients who received a placebo.
When compared to patients who received a placebo, patients treated with pitapat also exhibited a significant improvement in quality of life, as determined by instruments designed for each individual ailment. The most frequent side effects were headache and nausea (18% of patients in the mitapivat group and 23% of patients in the placebo group, respectively) (in 15 percent of patients in the mitapivat group and 33 percent of patients in the placebo group).
Because it targets the underlying issue to alleviate or eliminate anaemia and potentially prevent or reverse many of the other consequences associated with pyruvate kinase deficit, the researchers said the trial resulted in the first disease-modifying medicine for pyruvate kinase deficiency.