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Up to about 2.5 years of treatment with <a href="https://alsnewstoday.com/cnm-au8/">CNM-Au8</a> in an open-label extension of the HEALEY ALS platform trial significantly reduced the risk of death for individuals with <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS) relative to a historical placebo group of patients from previous ALS clinical trials, according to new analyses.
These long-term analyses add to previous findings from the platform trial, which found the experimental therapy from <a href="https://clene.com/">Clene Nanomedicine</a> reduced the risk of death for these ALS patients by more than 90% compared with a placebo in the first six months.
Similar results were observed when pooled data from <a href="https://clinicaltrials.gov/ct2/show/NCT04414345">CNMAu8&#8217;s arm in HEALEY (NCT04414345)</a> and the <a href="https://clinicaltrials.gov/ct2/show/NCT04098406">RESCUE-ALS Phase 2 clinical trial (NCT04098406)</a> were compared with the historical placebo-treated patients.
“To show such profound survival improvement using the HEALEY ALS Platform Trial data set alone and a pooled HEALEY and RESCUE data set is remarkable,&#8221; Benjamin Greenberg, MD, head of medical at Clene, said in a <a href="https://www.globenewswire.com/news-release/2023/09/25/2748500/0/en/Clene-Reports-Significant-Long-Term-Survival-Improvement-From-CNM-Au8-Treatment-in-HEALEY-ALS-Platform-Trial-Compared-to-PRO-ACT-Historical-Controls.html">company press release</a>.
&#8220;Clene is extremely gratified to see this consistent long-term survival data from the HEALEY ALS Platform Trial [open-label extension], with a continued clean safety profile, adding to the totality of the survival evidence,” Greenberg added.
[recommended-reading id=83732]
<h3>New analyses also used data from RESCUE-ALS Phase 2 trial</h3>
CNM-Au8 is an oral liquid suspension of gold nanocrystals, which is expected to support the energetic needs of nerve cells and protect them against forms of cellular stress implicated in the neurodegenerative disease.
The ongoing <a href="https://clinicaltrials.gov/ct2/show/NCT04297683?term=HEALEY+ALS&amp;draw=2&amp;rank=1">HEALEY ALS Platform Trial (NCT04297683)</a>, launched in 2020, is designed to simultaneously test multiple <a href="https://alsnewstoday.com/experimental-treatments-for-als/">ALS treatment candidates</a> using a shared placebo group. This strategy helps to cut costs and accelerate therapeutic development.
Adults with ALS, with symptom onset in the prior three years, are screened through the trial&#8217;s master protocol, and if eligible, are randomly assigned to one of the trial arms that is actively enrolling. <a href="https://clinicaltrials.gov/ct2/show/NCT04297683?term=HEALEY+ALS&amp;draw=2&amp;rank=1#contacts">Recruitment</a> is ongoing across 67 study locations in U.S. sites.
A CNM-Au8 arm was among the trial&#8217;s first, and ultimately enrolled 161 patients. Of them, about 75% were randomly assigned to receive CNM-Au8 at doses of 30 mg or 60 mg for six months, while the other 25% were given a placebo. After the main trial, 92% of the participants continued on in an open-label extension (OLE) trial, where all were given CNM-Au8 at the 30 mg dose.
The main trial did not meet its main goal of slowing functional declines, nor did it demonstrate benefit in measures of lung function.
Still, exploratory analyses indicated that the 30 mg dose was associated with a more than 90% <a href="https://alsnewstoday.com/news/cnm-au8-found-lower-risk-death-als-healey-platform-trial/">lower risk of death</a> and combined risk of death or need for permanently assisted ventilation relative to a placebo after six months. It also was associated with a <a href="https://alsnewstoday.com/news/cnm-au8-delayed-clinical-worsening-als-patients-healey-trial/">74% lower risk</a> of overall clinical worsening.
Because the therapy&#8217;s placebo-controlled portion was just six months, it would be difficult to ascertain CNM-Au8&#8217;s potential long-term survival benefits for ALS patients across the OLE portion. A common solution to this issue is to compare the therapy to an external, historical placebo group.
In the new analyses, the researchers compared CMN-Au8 treatment data from the HEALEY trial with placebo-treated patients from PRO-ACT, the largest U.S. clinical database of previous ALS trials.
The database contains data from 29 completed Phase 2 and 3 ALS clinical trials, including records from more than 11,600 ALS patients.
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<h3>Treatment with CNM-Au9 led to 49% lower risk of death for patients</h3>
For the analysis, 59 people who were originally treated with CNM-Au8 30 mg in the placebo-controlled part of HEALEY were compared with matched placebo participants in the PRO-ACT database.
These results showed that CNM-Au8-treated participants demonstrated a statistically significant, 49% lower risk of death compared with PRO-ACT participants with up to 133 weeks, or about 2.5 years, of treatment.
A similar analysis was performed that pooled 82 CNM-Au8-treated patients across the HEALEY and RESCUE trials. Again, the therapy was associated with a statistically significant 59% reduction in mortality risk relative to matched placebo-treated patients from PRO-ACT.
[quote=&#8221;center&#8221;]Improved survival status is an important measure of drug effect. &#8230; We are pleased to see these data from our long-term follow-up as further support of a survival signal in our HEALEY ALS Platform Trial.[/quote]
Previous analyses from RESCUE and its <a href="https://clinicaltrials.gov/ct2/show/NCT05299658">open-label extension trial (NCT05299658)</a> have similarly indicated a <a href="https://alsnewstoday.com/news/cnm-au8-seen-to-extend-survival-by-more-than-1-5-years-in-als-trial/">survival benefit of CNM-Au8</a>.
&#8220;Improved survival status is an important measure of drug effect,&#8221; said Merit Cudkowicz, MD, neurology chair at Massachusetts General Hospital, director of the Sean M. Healey &amp; AMG Center for ALS, and the principal investigator of the HEALEY ALS Platform Trial.
&#8220;We are pleased to see these data from our long-term follow-up as further support of a survival signal in our HEALEY ALS Platform Trial,&#8221; Cudkowicz said.
Over more than 500 years of collective exposure to CNM-Au8 across ALS, <a href="https://multiplesclerosisnewstoday.com/multiple-sclerosis-overview/">multiple sclerosis</a>, and <a href="https://parkinsonsnewstoday.com/what-is-parkinsons-disease/">Parkinson&#8217;s disease</a> clinical trials and expanded access programs, no safety signals or serious adverse events from the experimental therapy have been observed.
“I am also happy to see how helpful a shared open-source dataset such as PRO-ACT is to the field to analyze data from the [open-label extension] portions of clinical trials,&#8221; Cudkowicz said.
&#8220;We encourage all companies working in ALS to contribute their data to PRO-ACT once their trial is complete. I want to also thank all the people with ALS who are part of clinical trials and are helping the community find new treatments,” she added.

Long-term ALS survival benefit with CNM-Au8 seen in trial analyses

Renowned neurologist and <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS) investigator Merit Cudkowicz, MD, of Massachusetts General Hospital has been named this year&#8217;s recipient of the <a href="https://www.mda.org/">Muscular Dystrophy Association</a> (MDA) Legacy Award for Achievement in Clinical Research.
The award, which recognizes outstanding accomplishments in neuromuscular research, will be presented March 20 at the 2023 MDA Clinical and Scientific Conference in Dallas.
<a href="https://www.mdaconference.org/">Registration</a> is open for in-person and virtual attendance of the March 19-22 event, which this year will focus on emerging technologies in genetic medicine.
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&#8220;We at the Muscular Dystrophy Association are extremely proud to honor Dr. Cudkowicz with the 2023 MDA Legacy Award for Achievement in Clinical Research,&#8221; Sharon Hesterlee, PhD, chief research officer at MDA, said in a <a href="https://www.mda.org/press-releases/mda-announces-recipient-of-2023-mda-legacy-award-for-achievement-in-clinical-research-is-merit-cudkowicz-md-msc-renowned-neurologist-and-clinical-researcher-in-als">press release from the organization</a>.
&#8220;Dr. Cudkowicz&#8217;s work throughout her career has been innovative and has led to incredible progress in our ability to test new therapies for ALS efficiently through clinical platform trials to accelerate treatments. Through her collaboration with researchers, medical teams, and patients at the center of it all, her work has inspired hope and the development of new therapies,&#8221; she said. &#8220;We&#8217;re proud to have been a supporter of her work since she was a fellow, and to continue to support our shared vision for a world without ALS.&#8221;
The award will be presented by Cudkowicz&#8217;s long-time mentor Stanley H. Appel, MD, a researcher and neurologist who serves as the director of MDA&#8217;s <a href="https://www.mda.org/care/mda-care-centers">ALS Care Center</a> at Houston Methodist Neurological Institute.
&#8220;It&#8217;s an honor for me to receive the 2023 MDA Legacy Award for Achievement in Clinical Research, particularly at the MDA Clinical &amp; Scientific Conference in front of the global neuromuscular community. I&#8217;m grateful as well to have this presentation by one of my mentors, Dr. Stan Appel,&#8221; Cudkowicz said. &#8220;I received my very first grant from the Muscular Dystrophy Association, and Stan reviewed the first grants I ever wrote in ALS — and both have supported me throughout my career.
&#8220;I&#8217;m grateful for the continued commitment and dedication to finding a cure for ALS by the Muscular Dystrophy Association and for this recognition of the work we&#8217;re doing to accelerate treatments and find a cure to end this devastating disease.&#8221;
<h3>Innovations in ALS treatment</h3>
Director of the Sean M. Healey &amp; AMG Center for ALS, Cudkowicz is chief of neurology at Massachusetts General Hospital and is the Julieanne Dorn professor of neurology at Harvard Medical School. She is one of the founders and a previous co-chair of the Northeast ALS Consortium, a group of more than 134 clinical sites globally conducting collaborative ALS investigations.
Through innovations, Cudkowicz has helped accelerate development <a href="https://alsnewstoday.com/als-treatment/">ALS treatments</a>, including <a href="https://alsnewstoday.com/ionis-sod1-rx-biib067/">tofersen</a>, the first antisense oligonucleotide therapy for ALS associated with SOD1 mutations. She also has helped develop adaptive clinical trial designs and is principal investigator of the Clinical Coordination Center for <a href="https://neuronext.org/">NeuroNEXT</a>.
In addition, Cudkowicz <a href="https://alsnewstoday.com/news/first-patients-enrolled-pivotal-healey-als-platform-trial/">launched</a> the <a href="https://clinicaltrials.gov/ct2/show/NCT04297683?term=HEALEY&amp;draw=2&amp;rank=1">HEALEY ALS Platform Trial (NCT04297683)</a>, the first clinical trial in ALS testing multiple treatment candidates simultaneously with a goal of accelerating the development of therapies.
A mentor to many young neurologists in the field of ALS, Cudkowicz received an undergraduate degree in chemical engineering from the Massachusetts Institute of Technology, and a medical degree from Harvard Medical School.
&#8220;The Healey &amp; AMG Center for ALS at Mass General Hospital has worked collaboratively with MDA since the day we were formed and every advance in ALS has come with the support of MDA, including critical support of our clinic for multidisciplinary care, personalized care for patients and families, support for the Northeast ALS Consortium and innovative support for platform trials in ALS for patients,&#8221; said Cudkowicz. &#8220;This award helps shine a spotlight on our mission to accelerate how treatments are developed and find cures for people with ALS.&#8221;

ALS researcher Merit Cudkowicz to receive MDA legacy award

Treatment with <a href="https://alsnewstoday.com/cnm-au8/">CNM-Au8</a> significantly delayed clinical worsening in people with <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS), according to new exploratory analyses from the therapy&#8217;s arm of the HEALEY ALS platform trial.
The experimental therapy, from <a href="https://clene.com/">Clene Nanomedicine</a>, had previously been found to reduce the risk of death by more than 90% during the six-month trial.
Clene&#8217;s announcement of the new analyses comes on the heels of the latest data from the <a href="https://clinicaltrials.gov/ct2/show/NCT04098406">RESCUE-ALS Phase 2 trial (NCT04098406)</a> and its <a href="https://clinicaltrials.gov/ct2/show/NCT05299658">open-label extension part (NCT05299658)</a>. These studies demonstrated that a longer time on CNM-Au8 was associated with significantly <a href="https://alsnewstoday.com/news/slower-progression-experimental-als-treatment-cnm-au8/">slower disease progression</a> compared with a nine-month treatment delay.
The new findings are &#8220;highly encouraging,&#8221; Rob Etherington, Clene&#8217;s CEO, said in a <a href="https://www.globenewswire.com/news-release/2023/03/09/2623829/0/en/CNM-Au8-Associated-With-Delayed-Time-to-Key-Clinical-Progression-Events-at-Six-Months-Supporting-a-Survival-Benefit-in-the-Healey-ALS-Platform-Trial.html">company press release</a>, adding, &#8220;When supported by a confirmatory trial, this would give people living with ALS longer periods of independence, which are precious to them and their families.&#8221;
Etherington noted that the company will discuss the findings with the U.S. Food and Drug Administration, with the goal of identifying a path toward regulatory approval. Meanwhile, plans for a Phase 3 trial of CNM-Au8, called RESTORE-ALS, are underway.
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<h3>Therapy previously found to reduce risk of death more than 90%</h3>
CNM-Au8 is an oral liquid suspension of gold nanocrystals. It&#8217;s expected to support the energetic needs of nerve cells, protecting them against oxidative stress, a type of cellular damage implicated in ALS.
The novel <a href="https://clinicaltrials.gov/ct2/show/NCT04297683?term=HEALEY+ALS&amp;draw=2&amp;rank=1">HEALEY platform trial (NCT04297683)</a> is the first clinical study designed to simultaneously test several ALS treatment candidates — an approach expected to cut costs and accelerate the development of new therapies.
Adults with ALS who&#8217;ve had symptom onset within the last three years are screened through the trial&#8217;s master protocol. If found eligible, they are randomly assigned to one of the trial&#8217;s arms that is accepting new participants. <a href="https://clinicaltrials.gov/ct2/show/NCT04297683?term=HEALEY+ALS&amp;draw=2&amp;rank=1#contacts">Recruitment</a> is ongoing at dozens of sites in the U.S.
The <a href="https://clinicaltrials.gov/ct2/show/NCT04414345">CNM-Au8 trial arm (NCT04414345)</a> enrolled 161 patients who were randomly assigned to receive oral CNM-Au8 (30 mg or 60 mg) or a placebo, given daily for 24 weeks or about six months. Because HEALEY uses a shared placebo group, it allows 75% of participants in each arm to be given each investigational treatment.
The trial did not meet its main goal of slowing functional declines, as assessed by changes in the ALS Functional Rating Scale Revised (ALSFRS-R) scores. Nor did it demonstrate benefit in a joint assessment of survival and disease progression or measures of lung function.
Still, exploratory analyses showed that CNM-Au8 at its 30 mg dose reduced the risk of death, and the combined risk of death and need for permanently assisted ventilation, by more than 90% after six months.
Now the new analyses show that 30 mg of CNM-Au8 also significantly reduced the risk of overall clinical worsening by 74%. This measure assesses the risk of death, breathing tube placement, need for assisted ventilation for more than 22 hours a day, or feeding tube placement.
Individually, the risk of each of these measures also decreased with the experimental treatment.
In particular, the risk of feeding tube placement and the risk of death or permanent ventilation assistance were both significantly reduced — by 74% and 98%, respectively. Other, non-significant risk reductions also were observed for death (95%), assisted ventilation (63%), ALS-related hospitalizations (84%), and all-cause hospitalizations (69%).
Analyses taking into account patients&#8217; blood levels of neurofilament light chain, a biomarker of nerve cell damage, led to similar reductions, Clene noted.
Additionally, the treatment was found to be well tolerated, with no significant safety issues reported.
After completing the six-month trial, participants could join an open-label extension phase, in which all are receiving the 30 mg dose of CNM-Au8.
[quote align=&#8221;center&#8221;]When supported by a confirmatory trial, this would give people living with ALS longer periods of independence, which are precious to them and their families.[/quote]
Additional analyses from the HEALEY trial are planned, including an examination of disease progression biomarkers, as well as assessments of clinical worsening and survival in the extension phase. Overall, these findings will inform the design of future trials, according to Clene.
The benefits of the treatment identified thus far &#8220;could prove to be profoundly beneficial to people living with ALS and their families,” said Merit Cudkowicz, MD, the principal investigator of the HEALEY study. Cudkowicz also is the director of the Sean M. Healey &amp; AMG Center for ALS, and chief of the department of neurology at Massachusetts General Hospital in Boston.
“We hope to see these results persist and strengthen over an even longer-term follow-up period for patients who have entered the open-label portion of the trial, and for those individuals who will participate in Clene’s next ALS clinical trial,” Cudkowicz said.
James Berry, MD, the co-lead investigator for the CNM-Au8 trial arm, said the new results &#8220;provide ample rationale to continue its development in a Phase 3 ALS trial.&#8221;
&#8220;We would like to thank the hundreds of people living with ALS and their loved ones and caregivers, who have dedicated themselves to participation in this trial, and we look forward to learning more about the impact of CNM-Au8 on ALS progression in the future,” Berry added.

Tag: HEALEY ALS Platform Trial

Long-term ALS survival benefit with CNM-Au8 seen in trial analyses

ALS researcher Merit Cudkowicz to receive MDA legacy award

CNM-Au8 found to delay clinical worsening in ALS HEALEY trial