A SUPER-powered WP Engine Atlas Test Site

Joe&#039;s Atlas Experimentation Site

<a href="https://apellis.com/">Apellis Pharmaceuticals</a>’ investigational therapy <a href="https://apellis.com/our-science/our-pipeline/">pegcetacoplan</a> (APL-2) has failed to improve a combined assessment of function and survival in people with <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS), according to top-line data from the MERIDIAN Phase 2 clinical trial.
While the treatment was well tolerated, consistent with its established safety profile, the findings mean MERIDIAN failed to meet its primary goal. Other key secondary goals, including disease progression and changes in muscle strength and lung function, also were not met.
Apellis and <a href="https://www.sobi.com/en">Sobi</a>, which owns exclusive rights to the medication outside the U.S., plan to discontinue pegcetacoplan&#8217;s development for ALS, based on its lack of effectiveness.
The announcement follows a recent <a href="https://alsnewstoday.com/news/apellis-discontinues-dosing-pegcetacoplan-als-trial-data-review/">decision to discontinue</a> pegcetacoplan treatment in MERIDIAN&#8217;s open-label portion after the trial&#8217;s independent data monitoring committee concluded the available results didn&#8217;t support its continuation.
“We are disappointed in the outcome of the MERIDIAN study, especially on behalf of the ALS community who has been waiting for new treatments for this complex and unrelenting disease,” Jeffrey Eisele, PhD, chief development officer at Apellis, said in a <a href="https://www.globenewswire.com/news-release/2023/05/25/2675976/0/en/Apellis-Reports-Top-Line-Results-from-Phase-2-MERIDIAN-Study-in-ALS.html">company press release</a>. “We would like to sincerely thank the study participants and their caregivers from around the world who contributed to this important research.&#8221;
<a href="https://alsnewstoday.com/causes-of-als/">ALS is caused</a> by the progressive damage and loss of motor neurons, the nerve cells that control voluntary movement. The exact mechanisms leading to the disease aren&#8217;t fully understood, but inflammation is believed to be a key driver of its progression.
[recommended-reading id=38010]
<h3>Main, secondary goals in pegcetacoplan study</h3>
Pegcetacoplan is an inhibitor of the complement protein 3 (C3), a component of the complement system. This is a part of the immune system that&#8217;s normally involved in fighting infections.
In ALS, high levels of C3 are present at the neuromuscular junctions — the sites where nerve cells communicate with muscles – contributing to inflammation and the death of motor neurons.
The <a href="https://www.clinicaltrials.gov/ct2/show/NCT04579666">MERIDIAN Phase 2  trial (NCT04579666)</a> was designed to test pegcetacoplan in <a href="https://alsnewstoday.com/forms-of-als/sporadic-als/">sporadic ALS</a> patients whose <a href="https://alsnewstoday.com/als-symptoms/">symptoms</a> had started in the past 18 months.
A total of 249 participants were enrolled at dozens of sites in the U.S., Europe, Australia, and Japan. They were randomly assigned to receive pegcetacoplan or a placebo via injections under the skin twice a week for a year. All the participants were able to continue receiving their standard of care <a href="https://alsnewstoday.com/approved-treatments-for-als/">treatment for ALS</a> during the trial.
The trial&#8217;s main goal was to determine pegcetacoplan&#8217;s impact on a combined assessment of function and survival (CAFS), which ranks patients’ clinical outcomes based on survival time and changes in the ALS Functional Rating Scale–Revised (ALSFRS-R) score, a measure of functional decline.
Secondary goals included safety, changes in lung function and muscle strength, and functional decline. The time to death or needing respiratory support as well as the number of patients with suicidal thoughts were also assessed.
The study failed to met its primary and secondary goals, according to the company. Full MERIDIAN data is now being analyzed and is expected to be presented at a future medical meeting.
“Our hope is that the data generated from this study will continue to support future research and development in ALS,” Eisele said.

Pegcetacoplan fails to improve ALS outcomes in MERIDIAN trial

<a href="https://apellis.com/">Apellis Pharmaceuticals</a> has discontinued treatment with <a href="https://apellis.com/our-science/our-pipeline/">pegcetacoplan</a> (APL-2), its investigational therapy for <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS), in the open-label stage of the MERIDIAN trial.
The <a href="https://investors.apellis.com/news-releases/news-release-details/update-open-label-portion-meridian-study-investigating-systemic">decision</a> follows a review of trial data by an independent data monitoring committee, which concluded that the available results did not support treatment continuation. No safety concerns were behind the committee’s decision.
The company now will continue to examine the full dataset from the randomized part of MERIDIAN, which was completed by all participants. Top-line results are expected in the coming months, and the data will help inform the next steps for pegcetacoplan in ALS, Apellis said in a <a href="https://www.globenewswire.com/news-release/2023/05/04/2662038/0/en/Apellis-Pharmaceuticals-Reports-First-Quarter-2023-Financial-Results.html">press release</a> announcing its first quarter results.
[recommended-reading id=83790]
<h3>Trial was testing safety, efficacy of pegcetacoplan</h3>
Pegcetacoplan is an inhibitor of the complement protein 3, known as C3, a key component of the complement system.
This system is a part of the body’s immune system, which is normally involved in fending off infections. However, an abnormal complement activation is linked with excessive inflammatory responses, which underlie multiple health conditions.
In ALS, high levels of C3 are present in the neuromuscular junctions, the sites where nerve cells and muscles communicate. This contributes to chronic inflammation and the death of motor neurons, the cells that control voluntary movement and are progressively lost in ALS.
The <a href="https://clinicaltrials.gov/ct2/show/NCT04579666?term=APL-2&amp;draw=3&amp;rank=14">MERIDIAN Phase 2  trial (NCT04579666)</a>, which <a href="https://alsnewstoday.com/news/dosing-begins-in-phase-2-study-of-pegcetacoplan-als/">began dosing</a> in late 2020, was designed to test pegcetacoplan in <a href="https://alsnewstoday.com/forms-of-als/sporadic-als/">sporadic ALS</a> patients whose <a href="https://alsnewstoday.com/als-symptoms/">symptoms</a> had started less than 18 months before enrollment.
A total of 249 participants were included and randomly assigned to receive 1,080 mg of pegcetacoplan or a placebo, given via under-the-skin (subcutaneous) injections twice a week for one year. All were allowed to continue on their current <a href="https://alsnewstoday.com/als-treatment/">ALS treatments</a>.
The trial’s main goal was to determine the impact of pegcetacoplan on a combined assessment of survival and changes in ALS Functional Rating Scores Revised (ALSFRS-R) scores, indicative of functional declines.
Secondary goals included measures of safety, and changes in physical ability, muscle strength, and lung function, as well as time to death or the need for ventilatory support. The proportion of patients with suicidal thoughts also was assessed.
Those who completed the trial’s randomized part could then join an open-label extension part, in which all received pegcetacoplan for one year. However, the data gathered so far has led the trial&#8217;s monitoring committee to recommend treatment discontinuation in that part.
MERIDIAN was registered as a potentially registrational trial. That means its results could potentially be used to support a request to regulatory agencies asking for the approval of pegcetacoplan for ALS.
&#8220;We want to thank all the people living with ALS and their caregivers who participated in the study and appreciate the partnerships built with the broader ALS community. We are committed to continuing our work together as we analyze the data generated from this study,&#8221; Apellis stated.
&#8220;A decision on next steps for the program will be made following the planned analysis of the full data,&#8221; the company added.

Tag: pegcetacoplan

Pegcetacoplan fails to improve ALS outcomes in MERIDIAN trial

Apellis stops dosing of pegcetacoplan in ALS trial after data review