• blood cell disorder

    From ScienceDaily@1:317/3 to All on Thursday, April 14, 2022 22:30:44
    blood cell disorder
    ACTIVATE trial generated positive safety and efficacy data for mitapivat.


    Date:
    April 14, 2022
    Source:
    Massachusetts General Hospital
    Summary:
    Results from a phase 3 clinical indicate that the oral drug
    mitapivat is safe and effective for treating adults with pyruvate
    kinase deficiency, a genetic condition that causes red blood cell
    destruction. The trial's results led to the drug's approval by
    the U.S. Food and Drug Administration in February.



    FULL STORY ========================================================================== Researchers have published the results of a clinical trial that led
    the U.S.

    Food and Drug Administration to recently approve mitapivat for
    the treatment of adults with pyruvate kinase deficiency -- a rare
    genetic condition that leads to the destruction of red blood cells,
    or hemolytic anemia. The primary results from the global, phase 3,
    randomized, placebo-controlled ACTIVATE trial, which was conducted by
    an international team including investigators at Massachusetts General
    Hospital (MGH), are published in the New England Journal of Medicine.


    ==========================================================================
    "The lifelong anemia associated with pyruvate kinase deficiency results
    in chronic fatigue, reduced exercise tolerance, and a reduced ability
    to concentrate at work or school, which can make it a challenge to
    get through even a normal day," says lead author Hanny Al-Samkari,
    MD, a hematologist and clinical investigator at MGH and an assistant
    professor of Medicine at Harvard Medical School. "Moreover, most patients develop other potentially serious complications, like iron overload in
    the liver and/or heart (which can cause cancer or death), osteoporosis, gallbladder disease, blood clots, and other issues." Pyruvate kinase deficiency is characterized by mutations in the PKLRgene that encodes the pyruvate kinase enzyme in red blood cells. This enzyme is critical for maintaining red blood cells' energy levels and, therefore, their normal
    life span. Mitapivat can activate and stabilize the mutated pyruvate
    kinase that's expressed in patients' red blood cells, thereby restoring
    the enzyme's activity.

    "This is a 'disease modifying' therapy because it targets the underlying problem to improve or eliminate anemia and potentially prevent or
    reverse many of the other complications associated with pyruvate
    kinase deficiency," says Al-Samkari. "It is the first disease-modifying medication for pyruvate kinase deficiency, which up until now has been
    treated only with supportive measures like blood transfusion or removing
    a patient's spleen." In the ACTIVATE trial designed and conducted by Al-Samkari and his colleagues, 80 patients were randomized to receive
    either mitapivat (5 mg twice daily, with potential escalation to 20 or
    50 mg twice daily) or placebo for 24 weeks. The primary end point was
    a hemoglobin response (an indicator of red blood cell levels) that was sustained at two or more scheduled assessments at weeks 16, 20, and 24.

    Sixteen of the 40 patients (40%) who received mitapivat had a
    hemoglobin response, compared with none of the patients who received
    placebo. Patients who received mitapivat also had a greater response
    than those who received placebo with respect to secondary end points,
    which included other markers of red blood cell health. Patients treated
    with mitapivat also had a significant improvement in quality of life
    compared with patients receiving placebo as measured by disease-specific instruments.

    The most common adverse events were nausea (in 18% of patients in the
    mitapivat group and 23% of patients in the placebo group) and headache
    (in 15% of patients in the mitapivat group and 33% of patients in the
    placebo group).

    "The opportunity to develop a disease-modifying therapy for a disease
    like pyruvate kinase deficiency not only helps patients with this
    disease but also brings hope to patients with other similar disorders,"
    says Al-Samkari.

    "Because energy is everything to red blood cells, this drug may
    help patients with more common anemias like sickle cell disease
    and thalassemia. We are looking at this right now in other clinical
    trials, and early studies have been very promising." Additional study
    authors include Fre'de'ric Galacte'ros, MD, PhD, Andreas Glentho/j, MD, Jennifer A. Rothman, MD, Oliver Andres, MD, Rachael F. Grace, MD, Marta Morado-Arias, MD, D. Mark Layton, M.B., BS, Koichi Onodera, MD, Madeleine Verhovsek, MD, Wilma Barcellini, MD, Satheesh Chonat, MD, Malia P.

    Judge, BS, Erin Zagadailov, PharmD, Rengyi Xu, PhD,?Peter Hawkins, PhD,
    Vanessa Beynon, MD, Sarah Gheuens, MD, PhD, and Eduard J. van Beers, MD.

    This work was supported by Agios Pharmaceuticals.


    ========================================================================== Story Source: Materials provided by Massachusetts_General_Hospital. Note: Content may be edited for style and length.


    ========================================================================== Journal Reference:
    1. Hanny Al-Samkari, Fre'de'ric Galacte'ros, Andreas Glentho/j,
    Jennifer A.

    Rothman, Oliver Andres, Rachael F. Grace, Marta Morado-Arias,
    D. Mark Layton, Koichi Onodera, Madeleine Verhovsek, Wilma
    Barcellini, Satheesh Chonat, Malia P. Judge, Erin Zagadailov,
    Rengyi Xu, Peter Hawkins, Vanessa Beynon, Sarah Gheuens, Eduard
    J. van Beers. Mitapivat versus Placebo for Pyruvate Kinase
    Deficiency. New England Journal of Medicine, 2022; 386 (15):
    1432 DOI: 10.1056/NEJMoa2116634 ==========================================================================

    Link to news story: https://www.sciencedaily.com/releases/2022/04/220414110900.htm

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