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<a href="https://alsnewstoday.com/amx0035">Relyvrio</a> (sodium phenylbutyrate and taurursodiol), an approved treatment for people with <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS), has failed to meet its primary goal of slowing disease progression in an ongoing Phase 3 clinical trial designed to confirm its effectiveness.
That&#8217;s according to new data from the trial, dubbed PHOENIX, released today by the therapy&#8217;s developer, <a href="https://www.amylyx.com/">Amylyx Pharmaceuticals</a>.
Essentially, the data show that patients who received Relyvrio in addition to their standard ALS medications in PHOENIX experienced a similar rate of disease progression as did those given a standard treatment alone.
Based on the data, Amylyx is voluntarily pausing promotion of Relyvrio, and said it will work with regulatory authorities and the broader ALS community to determine the appropriate next steps for the therapy — which may include voluntarily withdrawing it from the market, according to a <a href="https://www.businesswire.com/news/home/20240308462671/en/Amylyx-Pharmaceuticals-Announces-Topline-Results-From-Global-Phase-3-PHOENIX-Trial-of-AMX0035-in-ALS">company press release</a>.
Until then, the therapy will remain available to ALS patients in the U.S. and in Canada, where it&#8217;s marketed under the brand name Albrioza. The company also will continue running its support programs to help patients on the medication, formerly known as AMX0035 for ALS, which has been <a href="https://alsnewstoday.com/news/relyvrio-amx0035-approved-us-als-treatment/">approved since 2022</a> in both countries.
[quote=&#8221;center&#8221;]Over the next eight weeks, our team will continue to engage with regulatory authorities and the ALS community to discuss the results from PHOENIX.[/quote]
Justin Klee and Joshua Cohen, co-CEOs of Amylyx, said they were &#8220;surprised and deeply disappointed by the PHOENIX results.&#8221;
&#8220;Our main priority at the moment is sharing the information with people living with ALS and their treating physicians; this is part of our continued commitment to them and our mission. Over the next eight weeks, our team will continue to engage with regulatory authorities and the ALS community to discuss the results from PHOENIX,&#8221; Klee and Cohen said.
The CEOs said their discussions with regulators will be informed by &#8220;two key principles: doing what is right for people living with ALS, informed by regulatory authorities and the ALS community, and by what the science tells us.&#8221;
[recommended-reading id=87478]
<h3>Regulators in Europe had recommended against therapy&#8217;s approval</h3>
Relyvrio was approved in the U.S. and Canada based mainly on data from a Phase 2 study called <a href="https://clinicaltrials.gov/ct2/show/NCT03127514">CENTAUR (NCT03127514)</a>. It tested the therapy against a placebo in 137 adults with recently-diagnosed, rapidly progressing ALS.
The results showed that, after six months, patients given Relyvrio had <a href="https://alsnewstoday.com/news-posts/2020/09/03/amx0035-safe-effective-in-slowing-als-functional-decline-trial-data-shows/">significantly less decline in physical function</a> than those on a placebo<a href="https://alsnewstoday.com/news-posts/2020/09/03/amx0035-safe-effective-in-slowing-als-functional-decline-trial-data-shows/">,</a> as measured by scores on the ALS Functional Rating Scale-Revised (ALSFRS-R).
Data from the Phase 2 study even hinted Relyvrio <a href="https://alsnewstoday.com/news/amx0035-survival-als-patients-centaur-clinical-trial-analysis-amylyx/">might extend survival</a> for ALS patients. The robustness of the results were questioned, however, with authorities in Europe recommending against approval based on data from the Phase 2 study alone.
The <a href="https://clinicaltrials.gov/ct2/show/NCT05021536">Phase 3 PHOENIX trial (NCT05021536)</a> was launched with the hope of definitively confirming that Relyvrio was effective as an ALS treatment. The study enrolled <a href="https://alsnewstoday.com/news/phoenix-trial-approved-als-therapy-relyvrio-amx0035-enrolled/">664 people with early ALS</a> who were randomly assigned to take Relyvrio or a placebo for about one year.
Because the Phase 3 trial included more patients and followed them for a longer period of time, it was expected that the results would be statistically more robust than in the smaller, shorter Phase 2 study.
The main goal of the PHOENIX trial was to show that patients given Relyvrio had less decline in ALSFRS-R scores, just as was seen in the Phase 2 CENTAUR study. However, the results showed that the Phase 3 trial failed to meet this goal: Rates of ALSFRS-R decline were not significantly different for patients given the therapy or the placebo.
[recommended-reading id=89981]
<h3>PHOENIX trial tested Relyvrio vs. a placebo in over 650 ALS patients</h3>
According to Amylyx, Relyvrio also failed to outperform the placebo across several secondary endpoints, or trial goals, which included patient-reported quality of life, assessments of lung function, and overall survival.
Still, Relyvrio was generally well tolerated in PHOENIX, and no unexpected safety issues were reported in the trial.
Full results from the Phase 3 trial are expected to be presented at an upcoming meeting and published in detail later this year. The company also is continuing to run an extension to the study in which European participants who completed PHOENIX could continue to receive Relyvrio.
The Amylyx CEOs thanked all those who took part in the therapy&#8217;s development, regardless of this trial&#8217;s outcome.
&#8220;On behalf of the entire Amylyx team, we are grateful to the ALS community and for the dedication of trial participants, investigators, and study site teams,&#8221; Klee and Cohen said.
&#8220;With data collected from 664 participants in PHOENIX, we are certain there will be important learnings that will help inform future ALS research,&#8221; they added.
While the next step for Relyvrio in ALS remain to be determined, the therapy will continue to be developed for other neurological disorders. Amylyx also will continue to advance its experimental ALS treatment <a href="https://alsnewstoday.com/news/als-mnd-2023-clinical-tests-aso-treatment-als-happen-next-year/">AMX0114</a>, which targets the calpain-2 protein.
&#8220;We are steadfast in our commitment to the ALS community and our mission, including with AMX0035 where it has shown potential in neurodegenerative diseases such as Wolfram syndrome and progressive supranuclear palsy, and with AMX0114, our investigational antisense oligonucleotide targeting calpain-2, in ALS,&#8221; Klee and Cohen said.

ALS treatment Relyvrio fails trial, may be withdrawn from market

On the heels of promising HEALEY-ALS Phase 2 trial data, <a href="https://www.prilenia.com/">Prilenia Therapeutics</a> plans to launch a pivotal Phase 3 study of <a href="https://alsnewstoday.com/pridopidine-experimental-treatment-als/">pridopidine</a>, its candidate <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS) treatment, in the second half of this year.
Relative to a placebo, pridopidine was associated with slower disease progression, a better life quality, and a potential to prolong survival in patients in early disease stages. These recently<a href="https://alsnewstoday.com/als-diagnosis/"> diagnosed ALS</a> patients with rapidly progressing symptoms saw particular benefit in terms of respiratory health and speech, although better speech was evident across all treated patients.
Prilenia reports it has completed discussions with global regulatory agencies regarding the next stage of pridopidine’s development.
“Based on the clinical data generated to date, pridopidine has the potential to become a meaningful treatment for ALS,” Michael R. Hayden, PhD, a physician, and CEO and founder of Prilenia, said in a <a href="https://www.businesswire.com/news/home/20240118053094/en/Prilenia-Announces-Clinical-Data-in-Support-of-its-Plans-to-Initiate-Global-Phase-3-Study-in-ALS">company press release</a>.
[recommended-reading id=89257]
<h3>&#8216;Active planning&#8217; underway for global clinical trial in ALS patients</h3>
“We believe it is important for Prilenia to advance our clinical program in ALS, and we are actively planning a single, global, pivotal Phase 3 clinical trial,” Hayden said.
Pridopidine is an oral small molecule designed to selectively bind to and activate the sigma-1 receptor (S1R), a protein involved in several processes critical to the function and survival of nerve cells.
Essentially, pridopidine aims to slow ALS progression by boosting the clearance of toxic molecules, increasing energy production, reducing cellular stress, and limiting inflammation.
The <a href="https://clinicaltrials.gov/ct2/show/NCT04297683">HEALEY ALS (NCT04297683)</a> platform trial is designed to simultaneously evaluate multiple experimental ALS treatments against a shared placebo group. It is being led by researchers at the Sean M. Healey &amp; AMG Center for ALS at Massachusetts General Hospital in Boston.
The <a href="https://clinicaltrials.gov/ct2/show/NCT04615923">Phase 2/3 pridopidine arm (NCT04615923)</a> enrolled 163 adults with clinically possible, probable, or definite ALS, whose symptoms had started within the last three years.
Participants were randomly assigned to oral pridopidine (45 mg) or a matched placebo taken twice daily for 24 weeks, or about six months. This was followed by an open-label extension study, where all participants received pridopidine.
The <a href="https://alsnewstoday.com/news/pridopidine-shows-some-potential-in-healey-trial-but-misses-main-goal/">pridopidine trial failed to meet its main goal</a> of demonstrating that treatment could slow functional decline relative to a placebo, reflected by changes in ALS Functional Rating Scale-Revised (ALSFRS-R) scores. Secondary goals related to muscle strength, respiratory function, and survival also were not met.
However, pridopidine led to significant improvements in certain speech measures, including speaking rate (how fast a person can speak) and articulation rate, or how quickly and clearly someone pronounces a word, after six months.
Additional analyses indicated that pridopidine&#8217;s use slowed ALSFRS-R declines in a subgroup of patients with definite ALS who were in an early disease course — within 1.5 years of symptom onset.
These patients experienced a significant, 2.4-point slower decline in ALSFRS-R scores compared with those given a placebo. Pridopidine was particularly effective at slowing changes on the ALSFRS-R respiratory domain, mainly on questions related to <a href="https://alsnewstoday.com/symptoms-of-als/#Breathing_difficulties">shortness of breath</a> (dyspnea).
Early ALS patients also experienced significantly slower declines in overall life quality compared with a placebo, with particular benefits in the eating/drinking and communication domains.
<h3>Particular benefit seen in HEALEY trial for those with fast progression</h3>
Even greater benefits were observed in the subset of probable or definite ALS patients who were early in the disease course but also considered to have fast-progressing disease. In this group, pridopidine was associated with a significant slowing of ALSFRS-R declines starting at week eight of treatment, and with a 5.2-point difference from a placebo after 24 weeks, corresponding to a 41% slower decline.
This subgroup of early, fast-progressing patients also showed the greatest improvements relative to a placebo in terms of changes on the ALSFRS-R respiratory domain, dyspnea, and speech.
Survival analyses spanning the main trial and its extension phase showed that pridopidine may increase survival time for those with definite or probable ALS in early disease phases.
Specifically, participants treated with pridopidine from the main trial&#8217;s start experienced a median survival of about 600 days (around 1.5 years), compared with a 300-day median survival for patients first randomized to a placebo, amounting to a 57% lower risk of death.
Pridopidine also was well tolerated with no serious treatment-related side effects reported.
Support for pridopidine’s continued development also may come from an <a href="https://alsnewstoday.com/news/nih-grant-supports-als-expanded-access-program-pridopidine/">ongoing expanded access program</a>. This study, <a href="https://clinicaltrials.gov/study/NCT06069934?term=pridopidine&amp;rank=1">(NCT06069934)</a>, is enrolling about 200 ALS patients in the U.S. who are not eligible to participate in clinical trials of pridopidine, all of whom will receive the therapy for up to two years.
&#8220;Our sincere appreciation to the many ALS patients, caregivers and healthcare providers who have contributed so much to our clinical studies as well as to those who will participate in future trials,&#8221; Hayden said.
Pridopidine has been designated an orphan drug in the U.S. and Europe for the treatment of ALS, a status that intends to help speed its clinical development. Prilenia is also developing pridopidine for <a href="https://huntingtonsdiseasenews.com/what-is-huntingtons-disease">Huntington’s disease</a>.

Phase 3 trial of oral pridopidine in treating ALS likely this year

Note: This story was updated Jan 24, 2024, to correct that Radicava and Radicava Oral Suspension are available in Switzerland but not in other European countries.
FAB122, an oral formulation of edaravone developed by <a href="https://www.ferrer.com/en">Ferrer</a>, failed to slow disease progression or extend survival in adults with <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS) who took part in a Phase 3 clinical trial.
The <a href="https://www.clinicaltrials.gov/study/NCT05178810">ADORE trial (NCT05178810)</a>, running across dozens of sites in Europe, was testing the formulation against a placebo, given as a daily dose of 100 mg for 48 weeks, on top of the standard of care for ALS.
“We are disappointed with this outcome and would like to thank the people with ALS, caregivers, investigators, and clinical trial staff for their participation in [the] ADORE clinical trial,” Tatjana Naranda, PhD, Ferrer’s chief research and development officer, said in a <a href="https://www.ferrer.com/en/results-study-ADORE-ALS">company press release</a>.
The company will terminate <a href="https://clinicaltrials.gov/study/NCT05866926">ADOREXT (NCT05866926)</a>, an open-label extension to the ADORE trial that was testing the long-term safety of FAB122 <a href="https://alsnewstoday.com/news/fnp122-oral-formulation-edaravone-enters-phase-3-extension/">for up to three years</a>.
“Although the results are not what we hoped for, our work to advance potentially transformative therapies in areas of high unmet need for people living with ALS will not stop,” Naranda said.
Edaravone protects nerve cells by neutralizing unstable molecules produced during metabolism called reactive oxygen species. When those unstable molecules build up in excess, they can damage nerve cells and contribute to the neurodegeneration seen in ALS.
The medication is available in the U.S. as <a class="c-link" href="https://alsnewstoday.com/radicava-edaravone-for-als/" target="_blank" rel="noopener noreferrer" data-stringify-link="https://alsnewstoday.com/radicava-edaravone-for-als/" data-sk="tooltip_parent">Radicava</a>, which is infused into the bloodstream, and as Radicava ORS, an oral suspension taken by mouth or via a feeding tube. Except for Switzerland, no European countries have approved either of these therapies.
[recommended-reading id=86605]
<h3>What were the goals of the ADORE trial?</h3>
FAB122, also called FNP122 and TWoo1, is a distinct formulation of edaravone that&#8217;s made of granules packaged in sachets to be dissolved in water. It was developed by the Dutch company <a href="https://treeway.nl/">Treeway</a>, who <a href="https://treeway.nl/ferrer-and-treeway-enter-into-licence-agreement-for-the-development-and-commercialisation-of-tw001-fnp122-for-amyotrophic-lateral-sclerosis/">licensed it to Ferrer</a> for clinical testing in Europe and some Asian countries.
ADORE recruited about 300 adults, ages 18-80, who&#8217;d had their first ALS symptoms within the last two years. It was conducted with the support of <a href="https://www.tricals.org/en/">Treatment Research Initiative to Cure ALS</a> (TRICALS), an European research initiative.
The trial&#8217;s main goal was to determine if adding FAB122 to standard ALS treatment could significantly slow disease progression, as assessed with the Revised ALS Functional Rating Scale (ALSFRS-R). Safety and the treatment&#8217;s impact on the Combined Assessment of Function and Survival (CAFS) were secondary measures. CAFS is a composite measure that ranks clinical outcomes based on survival and the rate of ALSFRS-R decline.
The treatment was safe and well tolerated, but failed to slow disease progression at 48 weeks compared with a placebo and didn&#8217;t improve CAFS outcomes at 48 and 72 weeks.
“At TRICALS, we had hoped for a different outcome of the ADORE study and are disappointed that this is not the positive result we all wanted,” said Leonard van den Berg, MD, PhD, chair of TRICALS. “We will continue to do our utmost to find a treatment for ALS as soon as possible.” Van den Berg is also professor of neurology at the University Medical Centre Utrecht in the Netherlands and was the trial’s principal investigator.
<a href="https://www.mt-pharma-america.com/">Mitsubishi Tanabe Pharma America</a>, the developer of Radicava and Radicava ORS, said FAB122 contains a distinct formulation of edaravone than that found in its products.
The clinical trial also had &#8220;many significant differences&#8221; from the Phase 3 trial that supported Radicava&#8217;s approval, so &#8220;any data and/or conclusions relative to FNP122 (FAB122) cannot be directly compared to [Radicava] or Radicava ORS,&#8221; the company said in a <a href="https://www.mt-pharma-america.com/media/news/press-releases/2024/01/17/mitsubishi-tanabe-pharma-america-inc-mtpa-statement-on-ferrers-phase-3-adore-clinical-trial-of-fnp122-fab122">press release</a>.

Edaravone formulation FAB122 fails to slow ALS progression

The U.S. Food and Drug Administration (FDA) has signed off on the chemistry, manufacturing, and controls (CMC) clinical development plan for <a href="https://www.neurosense-tx.com/">NeuroSense Therapeutics</a>&#8216; lead candidate for <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS) ahead of a planned Phase 3 study.
The Phase 3 trial of PrimeC is <a href="https://alsnewstoday.com/news/primec-potential-als-therapy-earns-patents-in-europe-japan-israel/">due to start in 2024</a> pending positive results from the company&#8217;s ongoing <a href="https://classic.clinicaltrials.gov/ct2/show/NCT05357950">PARADIGM Phase 2b clinical trial (NCT05357950)</a>, whose results are <a href="https://alsnewstoday.com/news/results-paradigm-trial-primec-als-expected-years-end/">expected in December</a>. CMC refers to the manufacturing practices and product specifications that must be followed and met to ensure product safety and consistency between batches.
&#8220;This confirmation from the FDA of our CMC strategy for a future pivotal Phase 3 clinical trial and commercial launch of PrimeC in the treatment of ALS marks a critical milestone in our drug development program,” Alon Ben-Noon, CEO of NeuroSense, said in a <a href="https://www.prnewswire.com/news-releases/neurosense-receives-us-fda-confirmation-of-cmc-strategy-for-primec-in-preparation-for-pivotal-phase-3-in-als-and-commercial-readiness-301986040.html">company press release</a>. “It sets the stage for a smooth transition, particularly as we anticipate clinical efficacy top-line results (secondary endpoints) from our Phase 2b trial very soon.&#8221;
<a href="https://www.neurosense-tx.com/primec/">PrimeC</a> is an oral, fixed-dose combination of ciprofloxacin, an antibiotic, and celecoxib, an anti-inflammatory. Both are approved in the U.S. for other indications. The compound&#8217;s combined action would block key mechanisms in ALS to slow <a href="https://alsnewstoday.com/stages-of-als/">disease progression</a>.
[recommended-reading id=86968]
<h3>What is PARADIGM trial assessing?</h3>
An initial formulation of PrimeC was deemed <a href="https://alsnewstoday.com/news/primec-safe-lowers-als-disease-biomarkers-phase-2-clinical-study/">safe and well tolerated</a>, in a <a href="https://clinicaltrials.gov/study/NCT04165850">Phase 2a clinical trial (NCT04165850)</a> with 15 ALS patients. After treatment, patients saw a slower decline in their functional and respiratory abilities over a historical group of untreated patients. Key ALS blood biomarkers, particularly TDP-43, also were reduced.
PARADIGM is assessing the safety and effectiveness of a longer-acting formulation of PrimeC, which would release the medications over time, requiring less frequent dosing.
A total of 69 ALS patients from Canada, Italy, and Israel were randomly assigned to a placebo or PrimeC for six months, while continuing with their standard <a href="https://alsnewstoday.com/als-treatment/">ALS treatments</a>. PrimeC was given at a total daily dose of 1,496 mg, taken as two tablets twice daily.
The trial will also measure PrimeC&#8217;s impact on key ALS blood biomarkers, TDP-43 and prostaglandin J2. Changes in functional disability, assessed by the ALS Functional Rating Scale-Revised (ALSFRS-R), as well as lung health, quality of life, and survival will also be assessed.
After completing six months of treatment in the trial&#8217;s randomized part, most patients (96%) joined an open label extension, where they are receiving PrimeC for a year.
The company plans to announce safety results and data from the trial&#8217;s secondary measures in December. Biomarker analyses, including those conducted in collaboration with Roche, are due in the first half of 2024.
PrimeC has received <a href="https://alsnewstoday.com/news/als-combination-therapy-primec-receives-fdas-orphan-drug-designation-enters-clinical-trials/">orphan drug status in the U.S.</a> and <a href="https://alsnewstoday.com/news/primec-orphan-drug-designation-europe-treatment-als/">the European Union</a>. The designation is meant to accelerate the development and regulatory review of rare disease therapies.

NeuroSense’s CMC earn FDA OK ahead of PrimeC Phase 3 trial

Treatment with <a href="https://alsnewstoday.com/ultomiris-ravulizumab-cwvz/">Ultomiris</a> (ravulizumab-cwvz) — a therapy approved for several rare diseases that works by blocking activation of part of the immune system called the complement cascade — failed to slow the progression of <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS) in a Phase 3 clinical trial that had been launched in 2020, a new study shows.
The study, which details the findings from the full 50-week trial data, supports the decision, made in 2021, to terminate that trial early.
&#8220;This trial rapidly showed that terminal complement &#8230; inhibition with [Ultomiris] did not slow functional decline in participants with ALS,&#8221; the researchers wrote.
<a href="https://alexion.com/">Alexion</a>, the therapy&#8217;s developer, ultimately stopped the trial in October 2021 after a pre-specified interim analysis failed to demonstrate any signs of efficacy from Ultomiris.
Titled &#8220;<a href="https://jamanetwork.com/journals/jamaneurology/fullarticle/2809453">Efficacy and Safety of Ravulizumab, a Complement C5 Inhibitor, in Adults With Amyotrophic Lateral Sclerosis: A Randomized Clinical Trial</a>,&#8221; the study was published in <a href="https://jamanetwork.com/journals/jamaneurology">JAMA Neurology</a>. The work was funded by Alexion, a subsidiary of AstraZeneca.
[recommended-reading id=72320]
<h3>CHAMPION-ALS study had enrolled 382 adults</h3>
The complement cascade is composed of a group of immune proteins that can become activated to destroy threats — but in some disorders, such activation can help to drive disease-causing inflammation.
Ultomiris, which works by blocking a complement protein called C5, is approved to treat several diseases that are driven by overactivation of the complement cascade, including <a href="https://myastheniagravisnews.com/ultomiris-ravulizumab-for-myasthenia-gravis/">myasthenia gravis</a> and <a href="https://pnhnews.com/ultomiris-ravulizumab-for-pnh/">paroxysmal nocturnal hemoglobinuria</a>, known as PNH.
Although the causes of ALS aren&#8217;t well understood, abnormal inflammation is thought to play a role, and some studies had suggested that complement activity may be increased in people with ALS.
Thus, Alexion sponsored a Phase 3 clinical trial called <a href="https://clinicaltrials.gov/ct2/show/NCT04248465">CHAMPION-ALS (NCT04248465</a>) to test whether Ultomiris treatment might be beneficial in ALS. The trial enrolled 382 adults with ALS, whose symptoms had started up to three years prior, and who were randomly assigned to receive Ultomiris or a placebo.
After two loading doses given two weeks apart, patients received treatment every eight weeks for up to 50 weeks, or nearly one year. All participants could then enroll in an open-label extension part and receive Ultomiris for up to 106 weeks, or a little more than two years.
The study&#8217;s main goal was to test whether Ultomiris could slow disease progression, measured by scores on the ALS Functional Rating Scale-Revised (ALSFRS-R).
[recommended-reading id=86121]
<h3>Initial preterm analysis had predicted failure of Ultomiris</h3>
In large studies like this, independent data monitoring committees will regularly conduct interim analyses testing for futility. Simply put, this involves looking at the available data to calculate whether there&#8217;s a reasonable likelihood the trial might have positive results.
In an interim analysis conducted after half of participants had completed their 26-week assessment, researchers found that the average ALSFRS-R score had worsened by 14.67 points for patients on Ultomiris — in fact showing slightly more worsening than the average of 13.33 points seen in the placebo group.
Statistical analyses suggested that the odds the trial would show slower progression with Ultomiris compared with the placebo was less than 0.1%, and the trial was ultimately terminated early.
[quote=&#8221;center&#8221;]There was a clear rationale for testing [Ultomiris] as a treatment for ALS based on preclinical and clinical evidence suggesting that C5 may be involved in disease progression. &#8230; However, the CHAMPION-ALS study was terminated when the week 26 interim analysis showed that the futility criterion had been met.[/quote]
The investigators now shared full analyses of all available trial data.
These results continued to show no effect of Ultomiris compared with a placebo on ALSFRS-R scores. There also was no benefit on other endpoints, including a combined assessment of survival and disease progression, changes in lung function, time to needing ventilatory support, and all-cause mortality.
Measures of muscle strength and markers of nerve damage also failed to improve with Ultomiris treatment.
A total of 80% of patients experienced side effects related to the therapy, the most common of which were headaches, falls, and constipation. Safety data showed no unexpected findings related to Ultomiris compared with what&#8217;s been seen with the therapy in people with other diseases.
&#8220;There was a clear rationale for testing [Ultomiris] as a treatment for ALS based on preclinical and clinical evidence suggesting that C5 may be involved in disease progression,&#8221; the researchers wrote.
&#8220;However,&#8221; they noted, &#8220;the CHAMPION-ALS study was terminated when the week 26 interim analysis showed that the futility criterion had been met.&#8221;
The researchers pointed that pharmacological data from the trial showed Ultomiris was blocking C5 as designed.
&#8220;It is unclear why C5 inhibition did not result in clinical benefit in patients with ALS and whether this lack of benefit might extend to other complement components,&#8221; they wrote.
The team concluded that this trial &#8220;highlights the unmet need for highly effective treatments to slow functional decline and extend survival in patients with ALS.&#8221;

Tag: Phase 3 clinical trial

ALS treatment Relyvrio fails trial, may be withdrawn from market

Phase 3 trial of oral pridopidine in treating ALS likely this year

Edaravone formulation FAB122 fails to slow ALS progression

NeuroSense’s CMC earn FDA OK ahead of PrimeC Phase 3 trial

Ultomiris failed to show benefit in ALS in clinical trial, per full data