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<label for="email-citation-format" class="action-panel-label">
Format:
</label>
<select id="email-citation-format" name="citation-format" class="action-panel-selector email-citation-format">
<option selected="selected" value="summary">Summary</option>
<option value="summary-text">Summary (text)</option>
<option value="abstract">Abstract</option>
<option value="abstract-text">Abstract (text)</option>
</select>
</div>
<div class="include-supplemental-container">
<input type="checkbox" aria-label="Include MeSH and other data" name="include-supplemental" id="email-include-supplemental" class="email-include-supplemental">
<label for="email-include-supplemental" class="email-include-supplemental-label">MeSH and other data</label>
</div>
<div class="form-field recaptcha ">
<div class="g-recaptcha" id="id-recaptcha" data-sitekey="6LfsWHMdAAAAAClKbtOpjQ2pMjgsGxvv7NdZW9uI"></div>
</div>
<div id="captcha-error-message" class="usa-input-error-message captcha-validation-message" role="alert"></div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Sending..."
data-ga-category="save_share"
data-ga-action="email"
data-ga-label="send">
Send email
</button>
<button class="action-panel-cancel"
aria-label="Close 'Email citations' panel"
ref="linksrc=close_email_panel"
aria-controls="email-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="email"
data-ga-label="cancel">
Cancel
</button>
</div>
<input type="hidden" name="email-search-details" value="" />
<input type="hidden" name="email-search-details-hash" value="0e42663a6c3bd85498fcb88798998fed7bfdc45d457db35281e41afe13cc0524" />
</form>
</div>
</div>
<div id="collections-action-panel"
class="collections-action-panel action-panel in-progress-dots-panel"
aria-hidden="true"
data-collections-open-panel-enabled="false"
data-collections-open-panel-url-hash="#open-collections-panel">
<div class="inner-wrap">
<h3 class="action-panel-heading">
Add to Collections
</h3>
<form id="collections-action-panel-form"
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-existing-collections-url="/list-existing-collections/"
data-add-to-existing-collection-url="/add-to-existing-collection/"
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
data-myncbi-max-collection-name-length="100"
data-add-to-collection-max-amount="1000"
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/">
<input type="hidden" name="csrfmiddlewaretoken" value="L80nPrUxOQO3YEcYASiXP7f5lwIUPg1B2VKsshnTorBxS5iOdbVZjfLJTAq6IRzV">
<div class="choice-group" role="radiogroup">
<ul class="radio-group-items">
<li>
<input type="radio"
id="collections-action-panel-new"
class="collections-new"
name="collections"
value="new"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="collections_radio_new">
<label for="collections-action-panel-new">Create a new collection</label>
</li>
<li>
<input type="radio"
id="collections-action-panel-existing"
class="collections-existing"
name="collections"
value="existing"
checked="true"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="collections_radio_existing">
<label for="collections-action-panel-existing">Add to an existing collection</label>
</li>
</ul>
</div>
<div class="controls-wrapper">
<div class="action-panel-control-wrap new-collections-controls">
<label for="collections-action-panel-add-to-new" class="action-panel-label required-field-asterisk">
Name your collection:
</label>
<input
type="text"
name="add-to-new-collection"
id="collections-action-panel-add-to-new"
class="collections-action-add-to-new"
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/"
maxlength="100"
data-ga-category="save_share"
data-ga-action="create_collection"
data-ga-label="non_favorties_collection">
<div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
Name must be less than 100 characters
</div>
</div>
<div class="action-panel-control-wrap existing-collections-controls">
<label for="collections-action-panel-add-to-existing" class="action-panel-label">
Choose a collection:
</label>
<select id="collections-action-panel-add-to-existing"
class="action-panel-selector collections-action-add-to-existing"
data-ga-category="save_share"
data-ga-action="select_collection"
data-ga-label="($('#collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'">
</select>
<div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your collection due to an error<br>
<a href="#">Please try again</a>
</div>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="add">
Add
</button>
<button class="action-panel-cancel"
aria-label="Close 'Add to Collections' panel"
ref="linksrc=close_collections_panel"
aria-controls="collections-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="bibliography-action-panel"
class="bibliography-action-panel action-panel in-progress-dots-panel"
aria-hidden="true"
data-bibliography-open-panel-enabled="false"
data-bibliography-open-panel-url-hash="#open-bibliography-panel">
<div class="inner-wrap">
<h3 class="action-panel-heading">
Add to My Bibliography
</h3>
<form id="bibliography-action-panel-form"
class="bibliography-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-add-to-bibliography-max-amount="100"
data-add-to-bibliography-batch-size="10"
data-bibliography-delegates-url="/list-bibliography-delegates/"
data-add-to-bibliography-url="/add-to-bibliography/"
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
data-mybib-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/">
<input type="hidden" name="csrfmiddlewaretoken" value="L80nPrUxOQO3YEcYASiXP7f5lwIUPg1B2VKsshnTorBxS5iOdbVZjfLJTAq6IRzV">
<div class="action-panel-control-wrap bibliographies-controls">
<div class="choice-group">
<ul class="bibliographies-action-add radio-group-items">
<li>
<input name="bibliography" id="my-bibliography" class="my-bibliography" type="radio" checked/>
<label for="my-bibliography">My Bibliography</label>
</li>
</ul>
</div>
</div>
<div class="bibliographies-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your delegates due to an error<br>
<a href="#">Please try again</a>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore>
Add
</button>
<button class="action-panel-cancel"
aria-label="Close 'Add to bibliography' panel"
ref="linksrc=close_bibliography_panel"
aria-controls="bibliography-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="mybib"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="saved-search-action-panel" class="saved-search-action-panel action-panel " aria-hidden="true"
data-saved-search-open-panel-enabled="false"
data-saved-search-open-panel-url-hash="#open-saved-search-panel">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Your saved search
</h2>
<form id="saved-search-action-panel-form"
class="saved-search-action-panel-form action-panel-content action-form"
data-create-saved-search-url="/create-saved-search/"
data-try-search-terms-url="/try-search-term/"
data-saved-search-root-url="https://www.ncbi.nlm.nih.gov/myncbi/searches/">
<input type="hidden" name="csrfmiddlewaretoken" value="L80nPrUxOQO3YEcYASiXP7f5lwIUPg1B2VKsshnTorBxS5iOdbVZjfLJTAq6IRzV">
<div class="action-panel-control-wrap">
<label for="saved-search-name" class="action-panel-label saved-search-name-label required-field-asterisk">
Name of saved search:
</label>
<input maxlength="200"
type="text"
name="saved-search-name"
id="saved-search-name"
class="saved-search-name"
value=""
required
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-term" class="action-panel-label required-field-asterisk">
Search terms:
</label>
<textarea name="saved-search-term" id="saved-search-term" class="saved-search-term" required></textarea>
</div>
<div class="test-search-term-wrap">
<a href="#" class="try-search-term">Test search terms</a>
</div>
<div class="choice-group action-panel-extra-margin-top">
<span class="action-panel-label" id="fieldset-label">
Would you like email updates of new search results?
</span>
<fieldset id="saved-search-alert" aria-describedby="fieldset-label">
<legend class="usa-sr-only">Saved Search Alert Radio Buttons</legend>
<ul class="radio-group-items">
<li>
<input type="radio" id="saved-search-alert-yes" class="saved-search-alert-yes" name="saved-search-alert" value="yes" checked>
<label for="saved-search-alert-yes" class="action-panel-label">Yes</label>
</li>
<li>
<input aria-label="No radio input" type="radio" id="saved-search-alert-no" class="saved-search-alert-no" name="saved-search-alert" value="no">
<label for="saved-search-alert-no" class="action-panel-label">No</label>
</li>
</ul>
</fieldset>
</div>
<div class="alert-schedule-wrap">
<div class="action-panel-control-wrap">
<label class="action-panel-label">
Email:
</label>
<span aria-label="Email address" id="saved-search-email" class="action-panel-label"><span class="action-panel-label-bold"></span> (<a class="myncbi-account-settings" href="https://www.ncbi.nlm.nih.gov/account/settings/">change</a>)</span>
</div>
<div class="action-panel-control-wrap action-panel-extra-margin-top">
<label for="saved-search-frequency" class="action-panel-label">
Frequency:
</label>
<select id="saved-search-frequency" class="no-border-panel-selector saved-search-frequency">
<option value="monthly">Monthly</option>
<option value="weekly">Weekly</option>
<option value="daily">Daily</option>
</select>
</div>
<div class="action-panel-control-wrap saved-search-monthly-additional">
<label for="saved-search-monthly-on-day" class="action-panel-label">
Which day?
</label>
<select id="saved-search-monthly-on-day" class="no-border-panel-selector">
<option value="Sunday">The first Sunday</option>
<option value="Monday">The first Monday</option>
<option value="Tuesday">The first Tuesday</option>
<option value="Wednesday">The first Wednesday</option>
<option value="Thursday">The first Thursday</option>
<option value="Friday">The first Friday</option>
<option value="Saturday">The first Saturday</option>
<option value="day">The first day</option>
<option value="weekday">The first weekday</option>
</select>
</div>
<div class="action-panel-control-wrap saved-search-weekly-additional">
<label for="saved-search-weekly-on-day" class="action-panel-label">
Which day?
</label>
<select id="saved-search-weekly-on-day" class="no-border-panel-selector saved-search-weekly-on-day">
<option value="Sunday">Sunday</option>
<option value="Monday">Monday</option>
<option value="Tuesday">Tuesday</option>
<option value="Wednesday">Wednesday</option>
<option value="Thursday">Thursday</option>
<option value="Friday">Friday</option>
<option value="Saturday">Saturday</option>
</select>
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-report" class="action-panel-label">
Report format:
</label>
<select id="saved-search-report" class="no-border-panel-selector saved-search-report">
<option value="DocSum">Summary</option>
<option value="DocSumText">Summary (text)</option>
<option value="Abstract">Abstract</option>
<option value="AbstractText">Abstract (text)</option>
<option value="MEDLINE">PubMed</option>
</select>
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-amount" class="action-panel-label">
Send at most:
</label>
<select id="saved-search-amount" class="no-border-panel-selector saved-search-amount">
<option value="1">1 item</option>
<option value="5" selected>5 items</option>
<option value="10">10 items</option>
<option value="20">20 items</option>
<option value="50">50 items</option>
<option value="100">100 items</option>
<option value="200">200 items</option>
</select>
</div>
<div>
<input type="checkbox" id="saved-search-send-if-no-result" class="saved-search-send-if-no-result" name="saved-search-send-if-no-result">
<label for="saved-search-send-if-no-result" class="action-panel-label smaller-checkbox">
Send even when there aren't any new results
</label>
</div>
<div class="action-panel-control-wrap option-text-in-email-wrap">
<label for="saved-search-email-text" class="action-panel-label">
Optional text in email:
</label>
<textarea name="saved-search-email-text"
id="saved-search-email-text"
class="saved-search-email-text"></textarea>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Saving..."
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="save">
Save
</button>
<button class="action-panel-cancel"
aria-label="Close 'Your saved search' panel"
ref="linksrc=close_saved_search_panel"
aria-controls="saved-search-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="citation-manager-action-panel" class="citation-manager-action-panel action-panel" aria-hidden="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Create a file for external citation management software
</h2>
<form id="citation-manager-action-panel-form"
class="action-panel-content action-form"
action="/results-export-ids/"
data-by-search-action="/results-export-search-data/"
data-by-ids-action="/results-export-ids/"
method="post"
data-by-search-method="post"
data-by-ids-method="post">
<input type="hidden" name="csrfmiddlewaretoken" value="L80nPrUxOQO3YEcYASiXP7f5lwIUPg1B2VKsshnTorBxS5iOdbVZjfLJTAq6IRzV">
<input name="results-format" type="hidden" value="pubmed"/>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Sending..."
data-ga-category="save_share"
data-ga-action="citation_manager"
data-ga-label="save">
Create file
</button>
<button class="action-panel-cancel"
aria-label="Close 'Send citations to citation manager' panel"
ref="linksrc=close_citation_manager_panel"
aria-controls="citation-manager-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="citation_manager"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="rss-action-panel" class="rss-action-panel action-panel " aria-hidden="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Your RSS Feed
</h2>
<form id="rss-action-panel-form"
class="rss-action-panel-form action-panel-content action-form"
data-create-rss-feed-url="/create-rss-feed-url/"
data-search-form-term-value="">
<input type="hidden" name="csrfmiddlewaretoken" value="L80nPrUxOQO3YEcYASiXP7f5lwIUPg1B2VKsshnTorBxS5iOdbVZjfLJTAq6IRzV">
<div class="action-panel-control-wrap">
<label for="rss-name" class="action-panel-label required-field-asterisk">
Name of RSS Feed:
</label>
<input maxlength="200"
placeholder="Name"
type="text"
name="rss-name"
id="rss-name"
class="rss-name"
value=''
required
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</div>
<div class="rss-limit-wrap">
<div class="action-panel-control-wrap action-panel-extra-margin-top">
<label for="rss-limit" class="action-panel-label">
Number of items displayed:
</label>
<select id="rss-limit" class="no-border-panel-selector rss-limit">
<option value="5">5</option>
<option value="10">10</option>
<option value="15" selected="selected">15</option>
<option value="20">20</option>
<option value="50">50</option>
<option value="100">100</option>
</select>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Creating..."
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="save">
Create RSS
</button>
<button class="action-panel-cancel"
aria-label="Close 'Your RSS' panel"
ref="linksrc=close_rss_panel"
aria-controls="rss-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="cancel">
Cancel
</button>
</div>
<div class="action-panel-control-wrap rss-link-copy-wrap">
<label for="rss-link" class="usa-sr-only">RSS Link</label>
<input placeholder="Your RSS Feed Link" type="text" name="rss-link" id="rss-link" class="rss-link" title="RSS Link">
<button
type="button"
disabled
class="rss-link-copy-button disabled"
data-ga-category="save_share"
data-ga-action="rss"
data-ga-label="copy">
Copy
</button>
</div>
</form>
</div>
</div>
</div>
</div>
<div class="article-page" id="article-page" data-article-pmid="38573482">
<aside class="page-sidebar">
<div class="inner-wrap">
<div class="full-text-links">
<div class="full-view">
<h3 class="title">
Full text links
</h3>
<div class="full-text-links-list">
<a class="link-item
dialog-focus"
href="https://dx.doi.org/10.1007/s12325-024-02827-8"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=False&amp;PrId=3055&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=38573482&amp;db=pubmed&amp;nlmid=8611864"
title="See full text options at Springer"
data-ga-category="full_text"
data-ga-action="Springer"
data-ga-label="38573482"
><img src="https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--production.springer.de-OnlineResources-Logos-springerlink.gif" alt="Springer full text link"><span class="text">
Springer
</span></a><a class="link-item
pmc
"
href="https://pmc.ncbi.nlm.nih.gov/articles/pmid/38573482/"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=True&amp;PrId=3494&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=38573482&amp;db=pubmed&amp;nlmid=8611864"
title="Free full text at PubMed Central"
data-ga-category="full_text"
data-ga-action="PMC"
data-ga-label="38573482"
><span class="text">
Free PMC article
</span></a>
</div>
</div>
<div class="short-view">
<a href="#" class="full-text-links-button full-text-links-dialog-trigger">
Full text links
</a>
</div>
</div>
<div class="actions-buttons sidebar"><h3 class="title">Actions</h3><div class="inner-wrap"><button class="citation-button citation-dialog-trigger"
aria-label="Open dialog with citation text in different styles"
data-ga-category="save_share"
data-ga-action="cite"
data-ga-label="open"
data-all-citations-url="/38573482/citations/"
data-citation-style="nlm"
data-pubmed-format-link="/38573482/export/"><span class="button-label">Cite</span></button><link type="text/css" href="ncbi-overlay-block/src/overlay-block.css"><div class="collections-button-container" data-article-id="38573482" data-article-db="pubmed"><button class="collections-button collections-dialog-trigger"
aria-label="Save article in MyNCBI collections."
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_button"
data-collections-open-dialog-enabled="false"
data-collections-open-dialog-url="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F38573482%2F%23open-collections-dialog"
data-in-collections="false"><span class="button-label">Collections</span></button><div class="overlay" role="dialog"><div id="collections-action-dialog"
class="dialog collections-dialog"
aria-hidden="true"><div class="title">Add to Collections</div><div class="collections-action-panel action-panel"><form id="collections-action-dialog-form"
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-existing-collections-url="/list-existing-collections/"
data-add-to-existing-collection-url="/add-to-existing-collection/"
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
data-myncbi-max-collection-name-length="100"
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/"><input type="hidden" name="csrfmiddlewaretoken" value="L80nPrUxOQO3YEcYASiXP7f5lwIUPg1B2VKsshnTorBxS5iOdbVZjfLJTAq6IRzV"><div class="choice-group" role="radiogroup"><ul class="radio-group-items"><li><input type="radio"
id="collections-action-dialog-new"
class="collections-new"
name="collections"
value="new"
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_radio_new"><label for="collections-action-dialog-new">Create a new collection</label></li><li><input type="radio"
id="collections-action-dialog-existing"
class="collections-existing"
name="collections"
value="existing"
checked="true"
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_radio_existing"><label for="collections-action-dialog-existing">Add to an existing collection</label></li></ul></div><div class="controls-wrapper"><div class="action-panel-control-wrap new-collections-controls"><label for="collections-action-dialog-add-to-new" class="action-panel-label required-field-asterisk">
Name your collection:
</label><input
type="text"
name="add-to-new-collection"
id="collections-action-dialog-add-to-new"
class="collections-action-add-to-new"
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/"
maxlength="100"
data-ga-category="collections_button"
data-ga-action="create_collection"
data-ga-label="non_favorties_collection"><div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
Name must be less than 100 characters
</div></div><div class="action-panel-control-wrap existing-collections-controls"><label for="collections-action-dialog-add-to-existing" class="action-panel-label">
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<h1 class="heading-title">
Safety and Efficacy of Pegcetacoplan in Adult Patients with Paroxysmal Nocturnal Hemoglobinuria over 48 Weeks: 307 Open-Label Extension Study
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><sup class="key">9</sup> Department of Hematology and Stem Cell Transplantation, West German Cancer Center, University Hospital Essen, Essen, Germany.</li>
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><sup class="key">10</sup> Department of Hematology, Ampang Hospital, Ampang, Malaysia.</li>
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><sup class="key">11</sup> Department of Clinical Haematology, The Royal Melbourne Hospital and Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.</li>
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><sup class="key">13</sup> Swedish Orphan Biovitrum AB, Stockholm, Sweden.</li>
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><sup class="key">14</sup> Lisa Tan Pharma Consulting Ltd, Cambridge, UK.</li>
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><sup class="key">15</sup> Center for Integrated Oncology, Aachen Bonn Cologne Düsseldorf (CIO ABCD), Aachen, Germany.</li>
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><sup class="key">16</sup> Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, University Hospital RWTH Aachen, Aachen, Germany.</li>
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<div class="publication-type" >Multicenter Study</div>
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Safety and Efficacy of Pegcetacoplan in Adult Patients with Paroxysmal Nocturnal Hemoglobinuria over 48 Weeks: 307 Open-Label Extension Study
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<span class="authors-list-item "><span class="full-name">Christopher J Patriquin</span><span class="citation-separator">&nbsp;et al.</span></span>
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</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Assistance Publique-Hôpitaux de Paris, Saint-Louis Hospital, Université Paris Cité, Paris, France." href="#short-view-affiliation-8" ref="linksrc=author_aff">
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><sup class="key">1</sup> Hematology &amp; Apheresis Medicine, University Health Network, Toronto General Hospital, Toronto, ON, Canada. Christopher.Patriquin@uhn.ca.</li>
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><sup class="key">2</sup> Clinic of Hematology, Clinical Center of Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.</li>
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><sup class="key">3</sup> Department of Haematology, St. James&#x27;s University Hospital, Leeds, UK.</li>
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><sup class="key">4</sup> Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.</li>
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id="short-view-affiliation-5"
><sup class="key">5</sup> Hematology Oncology of Indiana, Indianapolis, IN, USA.</li>
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id="short-view-affiliation-6"
><sup class="key">6</sup> Ascension St. Vincent Carmel, Carmel, IN, USA.</li>
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><sup class="key">7</sup> French Reference Center for Aplastic Anemia and Paroxysmal Nocturnal Hemoglobinuria, Paris, France.</li>
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><sup class="key">8</sup> Assistance Publique-Hôpitaux de Paris, Saint-Louis Hospital, Université Paris Cité, Paris, France.</li>
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id="short-view-affiliation-9"
><sup class="key">9</sup> Department of Hematology and Stem Cell Transplantation, West German Cancer Center, University Hospital Essen, Essen, Germany.</li>
<li data-affiliation-id="short-view-affiliation-10"
id="short-view-affiliation-10"
><sup class="key">10</sup> Department of Hematology, Ampang Hospital, Ampang, Malaysia.</li>
<li data-affiliation-id="short-view-affiliation-11"
id="short-view-affiliation-11"
><sup class="key">11</sup> Department of Clinical Haematology, The Royal Melbourne Hospital and Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.</li>
<li data-affiliation-id="short-view-affiliation-12"
id="short-view-affiliation-12"
><sup class="key">12</sup> Apellis Pharmaceuticals, Waltham, MA, USA.</li>
<li data-affiliation-id="short-view-affiliation-13"
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><sup class="key">13</sup> Swedish Orphan Biovitrum AB, Stockholm, Sweden.</li>
<li data-affiliation-id="short-view-affiliation-14"
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><sup class="key">14</sup> Lisa Tan Pharma Consulting Ltd, Cambridge, UK.</li>
<li data-affiliation-id="short-view-affiliation-15"
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><sup class="key">15</sup> Center for Integrated Oncology, Aachen Bonn Cologne Düsseldorf (CIO ABCD), Aachen, Germany.</li>
<li data-affiliation-id="short-view-affiliation-16"
id="short-view-affiliation-16"
><sup class="key">16</sup> Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, University Hospital RWTH Aachen, Aachen, Germany.</li>
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<p>
<strong class="sub-title">
Introduction:
</strong>
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, life-threatening disease characterized by complement-mediated hemolysis and thrombosis. Pegcetacoplan, the first targeted complement component 3 (C3) PNH therapy, was safe and efficacious in treatment-naive and pre-treated patients with PNH in five clinical trials.
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Methods:
</strong>
The 307 open-label extension (OLE) study (<a href="http://clinicaltrials.gov/show/NCT03531255" title="See in ClinicalTrials.gov">NCT03531255</a>) is a non-randomized, multicenter extension study of long-term safety and efficacy of pegcetacoplan in adult patients with PNH who completed a pegcetacoplan parent study. All patients received pegcetacoplan. Outcomes at the 48-week data cutoff (week 48 of 307-OLE or August 27, 2021, whichever was earlier) are reported. Hemoglobin concentrations, Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scores, and transfusion avoidance were measured. Hemoglobin &gt; 12 g/dL and sex-specific hemoglobin normalization (i.e., male, ≥ 13.6 g/dL; female, ≥ 12 g/dL) were assessed as percentage of patients with data available and no transfusions 60 days before data cutoff. Treatment-emergent adverse events, including hemolysis, were reported.
</p>
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<strong class="sub-title">
Results:
</strong>
Data from 137 patients with at least one pegcetacoplan dose at data cutoff were analyzed. Mean (standard deviation [SD]) hemoglobin increased from 8.9 (1.22) g/dL at parent study baseline to 11.6 (2.17) g/dL at 307-OLE entry and 11.6 (1.94) g/dL at data cutoff. At parent study baseline, mean (SD) FACIT-Fatigue score of 34.1 (11.08) was below the general population norm of 43.6; scores improved to 42.8 (8.79) at 307-OLE entry and 42.4 (9.84) at data cutoff. In evaluable patients, hemoglobin &gt; 12 g/dL occurred in 40.2% (43 of 107) and sex-specific hemoglobin normalization occurred in 31.8% (34 of 107) at data cutoff. Transfusion was not required for 114 of 137 patients (83.2%). Hemolysis was reported in 23 patients (16.8%). No thrombotic events or meningococcal infections occurred.
</p>
<p>
<strong class="sub-title">
Conclusion:
</strong>
Pegcetacoplan sustained long-term improvements in hemoglobin concentrations, fatigue reduction, and transfusion burden. Long-term safety findings corroborate the favorable profile established for pegcetacoplan.
</p>
<p>
<strong class="sub-title">
Trial registration:
</strong>
ClinicalTrials.gov identifier, <a href="http://clinicaltrials.gov/show/NCT03531255" title="See in ClinicalTrials.gov">NCT03531255</a>.
</p>
</div>
<p>
<strong class="sub-title">
Keywords:
</strong>
Clinical trial; Complement inhibitor; Eculizumab; FACIT-Fatigue; Hemoglobin; Open-label extension; Paroxysmal nocturnal hemoglobinuria (PNH); Pegcetacoplan; Thrombosis; Transfusion.
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<p xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:p1="http://pubmed.gov/pub-one">Michael Yeh is an employee of Apellis and holds stock options. Mohammed Al-Adhami was an employee of Apellis at the time of study completion. Christopher J. Patriquin reports relationships with Alexion, Apellis, Regeneron, Takeda, BioCryst, Swedish Orphan Biovitrum AB, Amgen, and Novartis. Andrija Bogdanovic reports relationships with Novartis, Takeda, Pfizer, and Apellis. Morag Griffin reports consultancy at Biocryst and Regeneron; honoraria from Alexion and Swedish Orphan Biovitrum AB; advisory board member at Novartis, Biocryst, Alexion, Amgen, and Swedish Orphan Biovitrum AB; and educational work sponsored by Apellis with unrestricted grant paid to Medscape. Richard J. Kelly has received research funding from Novartis, reports consultancy for Swedish Orphan Biovitrum AB, sat on advisory boards for Alexion, AbbVie, Amgen, Jazz, Novartis, and Swedish Orphan Biovitrum AB, and received lecture fees from Alexion, Astellas, Amgen, Biologix, Jazz, and Swedish Orphan Biovitrum AB. Jaroslaw P. Maciejewski has nothing to disclose. Brian Mulherin has nothing to disclose. Régis Peffault de Latour has nothing to disclose. Alexander Röth reports personal fees from Alexion, Apellis, Kira, Novartis, Roche, Swedish Orphan Biovitrum AB, Sanofi, Bioverativ, and Grifols; and grants from Roche. Veena Selvaratnam has received consultant fees from Apellis. Jeffrey Szer reports consultancy at Novartis, Alexion, and Apellis; honoraria from Takeda, Pfizer, Novartis, Prevail Therapeutics, and Alexion; speakers bureau at Takeda, Pfizer, Novartis, and Alexion; and membership on an entitys board of directors or advisory committees at Prevail Therapeutics and Alexion. Regina Horneff is an employee of Swedish Orphan Biovitrum AB. Lisa Tan is a consultant for Swedish Orphan Biovitrum AB. Jens Panse reports consultancy and honoraria at Blueprint Medicines, Amgen, F. Hoffmann-La Roche, MSD, Bristol Myers Squibb, Alexion, AstraZeneca, Novartis, Pfizer, Gilead, Boehringer Ingelheim, Swedish Orphan Biovitrum AB, and Apellis; and honoraria from Swiss Biopharma.</p>
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Figures
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<p> Fig. 1 </p>
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<div class="figure-caption-contents"><p> Summary of the parent study… </p></div>
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<p> Fig. 1 </p>
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<div class="figure-caption-contents"><p> Summary of the parent study background and the subsequent 307-OLE of pegcetacoplan in… </p></div>
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Fig. 1
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<div class="figure-caption-contents">Summary of the parent study background and the subsequent 307-OLE of pegcetacoplan in patients with PNH. <i>C5</i> complement component 5, <i>OLE</i> open-label extension, <i>PNH</i> paroxysmal nocturnal hemoglobinuria, <i>SC</i> subcutaneous. <sup>a</sup>Source: de Castro and colleagues [27]. <sup>b</sup>Source: Wong and colleagues [28]. <sup>c</sup>Sources: Hillmen and colleagues [24], de Latour and colleagues [25]. <sup>d</sup>Patients had not received complement inhibitor treatment within 3 months prior to screening. <sup>e</sup>Source: Wong and colleagues [26]. <sup>f</sup>Supportive care included blood transfusions, anticoagulants, corticosteroids, and supplements (iron, folate, and vitamin B<sub>12</sub>). <sup>g</sup>Dosage increases were considered for patients with LDH&gt;2×the upper limit of normal on one occasion while receiving pegcetacoplan. Eculizumab and ravulizumab were permitted as rescue treatments for acute breakthrough hemolysis</div>
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<p> Fig. 2 </p>
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<div class="figure-caption-contents"><p> Concentrations of hemoglobin at baseline… </p></div>
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<div class="figure-caption-contents"><p> Concentrations of hemoglobin at baseline of the PALOMINO, PADDOCK, PEGASUS, and PRINCE parent… </p></div>
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Fig. 2
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<div class="figure-caption-contents">Concentrations of hemoglobin at baseline of the PALOMINO, PADDOCK, PEGASUS, and PRINCE parent studies and from 307-OLE entry to week 48 in the total and parent study populations of patients with PNH. <i>LLN</i> lower limit of normal, <i>NA</i> not available, <i>OLE</i> open-label extension, <i>PNH</i> paroxysmal nocturnal hemoglobinuria, <i>SD</i> standard deviation. <sup>a</sup>Hemoglobin LLN for female patients: 12 g/dL. <sup>b</sup>Patients in PALOMINO, PADDOCK, and PRINCE were complement inhibitor-naive at baseline. <sup>c</sup>Includes PHAROAH patients (<i>N</i>=4), unless noted. <sup>d</sup>Does not include PHAROAH patients</div>
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<p> Fig. 3 </p>
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<div class="figure-caption-contents"><p> Concentrations of LDH at baseline… </p></div>
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<p> Fig. 3 </p>
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<div class="figure-caption-contents"><p> Concentrations of LDH at baseline of the PALOMINO, PADDOCK, PEGASUS, and PRINCE parent… </p></div>
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Fig. 3
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<div class="figure-caption-contents">Concentrations of LDH at baseline of the PALOMINO, PADDOCK, PEGASUS, and PRINCE parent studies and from 307-OLE entry to week 48 in the total and parent study populations of patients with PNH. <i>IQR</i> interquartile range, <i>LDH</i> lactate dehydrogenase, <i>LLN</i> lower limit of normal, <i>NA</i> not available, <i>OLE</i> open-label extension, <i>PNH</i> paroxysmal nocturnal hemoglobinuria, <i>ULN</i> upper limit of normal. <sup>a</sup>Error bars for parent study baseline values were not included to maintain the scale. Patients in PALOMINO, PADDOCK, and PRINCE were complement inhibitor-naive at baseline. <sup>b</sup>Includes PHAROAH patients (<i>N</i>=4), unless noted. <sup>c</sup>Does not include PHAROAH patients</div>
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<p> Fig. 4 </p>
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<div class="figure-caption-contents"><p> Scores for FACIT-Fatigue at baseline… </p></div>
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<p> Fig. 4 </p>
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<div class="figure-caption-contents"><p> Scores for FACIT-Fatigue at baseline of the PALOMINO, PADDOCK, PEGASUS, and PRINCE parent… </p></div>
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Fig. 4
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<div class="figure-caption-contents">Scores for FACIT-Fatigue at baseline of the PALOMINO, PADDOCK, PEGASUS, and PRINCE parent studies and from 307-OLE entry to week 48 in the total and parent study populations of patients with PNH. <i>FACIT-Fatigue</i> Functional Assessment of Chronic Illness TherapyFatigue, <i>NA</i> not available, <i>OLE</i> open-label extension, <i>PNH</i> paroxysmal nocturnal hemoglobinuria, <i>SD</i> standard deviation. <sup>a</sup>Defined by Cella and colleagues [29]. A FACIT-Fatigue score increase5 points is considered a clinically meaningful improvement [31]. <sup>b</sup>Patients in PALOMINO, PADDOCK, and PRINCE were complement inhibitor-naive at baseline. <sup>c</sup>Includes PHAROAH patients (<i>N</i>=4), unless noted. <sup>d</sup>Does not include PHAROAH patients</div>
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<div class="figure-caption-contents"><p> Percentage of patients with transfusion… </p></div>
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<div class="figure-caption-contents"><p> Percentage of patients with transfusion avoidance <sup> a </sup> from 307-OLE entry to data cutoff… </p></div>
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<div class="figure-caption-contents">Percentage of patients with transfusion avoidance<sup>a</sup> from 307-OLE entry to data cutoff in the total and parent study populations of patients with PNH. <i>OLE</i> open-label extension, <i>PNH</i> paroxysmal nocturnal hemoglobinuria. <sup>a</sup>Patients who avoided transfusion did not require a transfusion during the treatment period to the data cutoff (i.e., the earliest of week 48 of the 307-OLE or August 27, 2021)</div>
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Three Years On: The Role of Pegcetacoplan in Paroxysmal Nocturnal Hemoglobinuria (PNH) since Its Initial Approval.
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<span class="docsum-journal-citation full-journal-citation">Int J Mol Sci. 2024 Aug 9;25(16):8698. doi: 10.3390/ijms25168698.</span>
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Kulasekararaj AG, Lazana I. Paroxysmal nocturnal hemoglobinuria: where are we going. Am J Hematol. 2023;98(Suppl 4):S33S43. doi: 10.1002/ajh.26882.
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Brodsky RA. Paroxysmal nocturnal hemoglobinuria. Blood. 2014;124:28042811. doi: 10.1182/blood-2014-02-522128.
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Hill A, Kelly RJ, Hillmen P. Thrombosis in paroxysmal nocturnal hemoglobinuria. Blood. 2013;121:49855105. doi: 10.1182/blood-2012-09-311381.
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Hillmen P, Hall C, Marsh JC, et al. Effect of eculizumab on hemolysis and transfusion requirements in patients with paroxysmal nocturnal hemoglobinuria. N Engl J Med. 2004;350:552559. doi: 10.1056/NEJMoa031688.
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