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Trial Co-led by Mass General Leads to Oral Drug Approval for Red Blood Cell Disorder

In This Article

  • Pyruvate kinase deficiency is a rare genetic condition that leads to the destruction of red blood cells, or hemolytic anemia
  • The condition has previously been treated only with supportive measures such as blood transfusion or splenectomy
  • A recent phase 3 trial conducted by Massachusetts General Hospital researchers and an international team investigated the use of an oral drug, mitapivat, for treatment of the condition
  • The trial's results indicate that mitapivat is safe and effective for treating adults with pyruvate kinase deficiency, leading to its approval by the FDA

Pyruvate kinase deficiency is a rare genetic condition that manifests as hemolytic anemia, leading to the destruction of red blood cells. Affected individuals can experience anemic symptoms like chronic fatigue, but most patients develop other complications such as osteoporosis, gallbladder disease, blood clots and more. Despite these serious complications, previous treatments for pyruvate kinase deficiency involved only supportive measures such as blood transfusion or removal of the spleen.

A recent phase 3 clinical study, the ACTIVATE trial, investigated the effectiveness of a potential disease-modifying oral drug, mitapivat. The trial was designed and conducted by an international team of researchers that included Hanny Al-Samkari, MD, hematologist and clinical investigator in the Center for Hematology at the Massachusetts General Hospital Cancer Center.

The results, published in the New England Journal of Medicine, indicate that mitapivat is safe and effective for treating adults with pyruvate kinase deficiency. Following those results, the FDA approved the drug for use in treating adults with this condition.

Pyruvate kinase deficiency is characterized by mutations in the PKLR gene that encodes the pyruvate kinase enzyme responsible for maintaining the normal lifespan of red blood cells. Mitapivat can stabilize the mutated pyruvate kinase and restore the enzyme's normal activity, leading to a hemoglobin response as an indicator of red blood cell health.

In this global, placebo-controlled trial, 80 patients were randomized to receive either mitapivat (5 mg twice daily, with the potential to escalate to 20 or 50 mg twice daily) or placebo for 24 weeks. The primary end point was a hemoglobin response sustained at two or more assessments, scheduled at weeks 16, 20 and 24.

Of the 40 patients who received mitapivat, 16 (40%) had a hemoglobin response. None of the patients who received placebo had a hemoglobin response. The mitapivat patients had a significant improvement in quality of life compared to placebo patients. Patients who received mitapivat also experienced a greater response to other markers of red blood cell health, compared to patients who received placebo.

The most common adverse events were:

  • Nausea—in 18% of mitapivat patients vs. in 23% of placebo patients
  • Headache—15% vs. 33%

Other clinical trials are currently investigating the drug's potential for the treatment of other common anemias, such as sickle cell disease and thalassemia.

Learn more about the Center for Hematology

Explore research at the Mass General Cancer Center


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Hanny Al-Samkari, MD, is a classical hematologist and clinical investigator at the Center for Hematology at the Mass General Cancer Center. Here he discusses his research on the use of systemic therapies to treat hereditary hemorrhagic telangiectasia.