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When investigational <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS) therapy <a href="https://alsnewstoday.com/cnm-au8/">CNM-Au8</a> reaches the bloodstream, it attracts a layer of proteins called a corona to its surface that help it more easily reach the brain and last longer in circulation, according to recent research.
Developer <a href="https://clene.com/">Clene Nanomedicine</a> says the findings are consistent with previous clinical and preclinical research indicating the oral treatment can reach the brain and exert its biological effects there.
“These new data show that the corona composition of the CNM-Au8 nanocrystals contribute further favorable drug properties to our neuroprotective agent, consistent with what we are seeing in our preclinical and clinical studies,” Mark Mortenson, chief science officer of Clene, said in a <a href="https://www.globenewswire.com/news-release/2024/03/15/2847014/0/en/Clene-Announces-Peer-Reviewed-Publication-Characterizing-the-Protein-Corona-of-the-Investigational-Neurodegenerative-Disease-Drug-CNM-Au8.html">company press release</a>.
The new research was published in a study, “<a href="https://pubs.acs.org/doi/10.1021/acsptsci.4c00028">Protein Corona Composition of Gold Nanocatalysts</a>,” in ACS Pharmacology &amp; Translational Science. Three of the study authors work at Clene.
[recommended-reading id=90348]
<h3>Clene seeking accelerated approval of CNM-Au8</h3>
At the end of last year, the company started talking with the U.S. Food and Drug Administration (FDA) about plans to seek approval of CNM-Au8 for ALS under the agency’s accelerated approval pathway.
In those discussions, the FDA indicated initial findings showing that a biomarker of nerve damage called neurofilament light chain (NfL) was reduced with the oral therapy in Phase 2 clinical trials were <a href="https://alsnewstoday.com/news/auto-draft-2/">not enough to support such an approval</a>.
The company is now preparing more recent data to address the agency&#8217;s questions, and plans to submit it to prompt accelerated approval discussions still this year.
“Having held our initial discussion with the FDA … we have a clear understanding of the additional data required to support an accelerated approval pathway filing for CNM-Au8,” Rob Etherington, Clene’s president and CEO, said in a <a href="https://www.globenewswire.com/en/news-release/2024/03/13/2845345/0/en/Clene-Reports-Full-Year-2023-Financial-Results-and-Recent-Operating-Highlights.html">separate press release</a>.
“We believe that we can provide additional supportive evidence to advance discussions with the FDA with the potential to file [a new drug application] later this year,” Etherington added.
The CEO noted such evidence will likely include biomarker data, as well as new findings related to clinical function and survival among ALS patients.
Indeed, accumulating evidence from clinical trials and <a href="https://alsnewstoday.com/news/cnm-au8-use-extends-als-survival-compassionate-use-studies/">compassionate use programs</a> suggest CNM-Au8 can <a href="https://alsnewstoday.com/news/long-term-survival-benefit-seen-cnm-au8-healey-als-analyses-trial/">extend survival</a> and <a href="https://alsnewstoday.com/news/cnm-au8-delayed-clinical-worsening-als-patients-healey-trial/">delay clinical worsening</a> among ALS patients.
[recommended-reading id=90252]
<h3>CNM-Au8 is an oral liquid suspension of gold nanoparticles</h3>
CNM-Au8 is an oral liquid suspension of gold nanoparticles that&#8217;s believed to slow ALS progression by supporting the energetic needs of nerve cells and protecting them against types of damage that contribute to the disease.
When nanoparticles reach the bloodstream, they become coated in a layer of proteins and other molecules, together called a corona. The properties of this corona can substantially influence the effects of the nanoparticles in the body.
Findings from the recent study showed when CNM-Au8 was exposed to human blood in the lab, a corona formed that was specifically enriched with apolipoproteins. These proteins are known to bind to the selective blood-brain barrier (BBB) and facilitate the transport of substances into the central nervous system (CNS), or the brain and spinal cord.
The BBB is a cellular layer that seeks to prevent potentially harmful substances circulating in the bloodstream from entering the CNS. It is a major hurdle when developing brain-targeted medications, as many are unable to breach the barrier.
“Our research underlines that these engineered gold nanocrystals … can form a distinct protein corona that facilitates access to brain tissue,” said Morteza Mahmoudi, PhD, of the Michigan State University College of Human Medicine and the study&#8217;s senior author.
[recommended-reading id=90466]
<h3>Corona lacked proteins capable of producing immune reaction</h3>
Moreover, the corona notably lacked proteins capable of producing immune responses in the body. In addition to causing inflammation, such reactions could cause the nanoparticles to be degraded and removed from circulation more quickly.
Taken together, these properties of the corona are critical for ensuring CNM-Au8&#8217;s &#8220;enhanced stability, prolonged circulation in the bloodstream, and improved ability to cross the BBB,&#8221; the researchers wrote.
According to Clene’s chief development officer and a study author, Michael Hotchkin, the findings are “notably consistent” with findings from clinical trials of CNM-Au8 in people with ALS, <a href="https://multiplesclerosisnewstoday.com/multiple-sclerosis-overview/">multiple sclerosis</a>, and <a href="https://parkinsonsnewstoday.com/what-is-parkinsons-disease/">Parkinson’s disease</a>.
“Across 500+ years of patient exposure in multiple Phase 2 clinical trials and expanded access programs, CNM-Au8 treatment has been shown to be safe and well-tolerated,” Hotchkin said.
“These prior clinical results are further enriched by the findings from this work explaining how the protein corona forms around CNM-Au8 once in the bloodstream, and how this corona preferentially aids access through the blood-brain barrier to support CNM-Au8’s activity in the brain,” he added.

Research identifies ways CNM-Au8 can effectively reach the brain

Treatment with <a href="https://alsnewstoday.com/cnm-au8/">CNM-Au8</a> was shown to significantly prolong survival — relative to the natural history of the disease — among people with advanced <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS) who took part in two expanded access programs (EAP), also known as compassionate use programs.
The findings from these EAPs, which allow an experimental therapy&#8217;s use in patients outside of clinical trials, are consistent with previous observations in Phase 2 studies that tested the oral therapy in less severely affected individuals with ALS.
“These EAP results help us better understand how people living with more advanced disease respond to treatment,” Richard S. Bedlack Jr., MD, PhD, a professor at the Duke University School of Medicine, in North Carolina, and a member of the steering committee for one of the EAP studies, said in a <a href="https://www.globenewswire.com/news-release/2024/02/22/2833653/0/en/Clene-Reports-Significant-Survival-Benefit-With-CNM-Au8-Treatment-in-ALS-EAP-Compassionate-Use-Programs.html">press release announcing the results</a>.
The data support developer <a href="https://clene.com/">Clene Nanomedicine</a>’s plans to advance CNM-Au8 to Phase 3 clinical testing, which the company has previously noted is expected to begin this year.
Clene last October also was awarded a four-year, $45.1 million grant from the National Institutes of Health to <a href="https://alsnewstoday.com/news/new-eap-makes-cnm-au8-available-als-patients-outside-trials/">support the launch of a third EAP</a>. That compassionate use program will particularly seek to reach U.S. patients in rural and remote areas virtually via a telemedicine platform. It&#8217;s expected to start enrolling in all 50 states during the first half of this year.
“Collecting data of peoples’ experience beyond clinical trials is extremely important in rare diseases like ALS,&#8221; Bedlack said, adding that the EAP data &#8220;warrant consideration to be included in Clene’s discussions about CNM-Au8 with regulatory agencies.”
[recommended-reading id=88296]
<h3>Compassionate use programs allow patients to get treatment outside trials</h3>
CNM-Au8 is an oral liquid suspension of gold nanoparticles. It aims to slow ALS progression by supporting nerve cells’ energy needs and protecting against types of cellular damage that are implicated in the neurodegenerative disease.
Phase 2 clinical trials of the therapy candidate are wrapping up, among them the <a href="https://clinicaltrials.gov/ct2/show/NCT04098406">RESCUE-ALS study (NCT04098406)</a> and its <a href="https://clinicaltrials.gov/ct2/show/NCT05299658">open-label extension (NCT05299658)</a>, as well as an arm of the <a href="https://clinicaltrials.gov/study/NCT04297683">HEALEY ALS platform trial (NCT04297683)</a>. RESCUE-ALS tested CNM-Au8 against a placebo in 45 patients, while its extension involved an estimated 40 individuals. In that open-label part, both researchers and participants know the exact medication that&#8217;s being given. The HEALEY ALS trial, meanwhile, is a multicenter, multi-regimen clinical trial evaluating several treatment candidates at the same time.
For their part, EAPs are regulated pathways that intend to offer access to an investigational therapy outside of clinical trial settings for patients with serious or life-threatening diseases for whom no satisfactory treatment is available.
The CNM-Au8 EAPs, both of which are still active, include patients in the U.S. who were not eligible for CNM-Au8 clinical trials — usually because their disease was too advanced.
The first <a href="https://clinicaltrials.gov/study/NCT04081714?cond=ALS&amp;intr=CNM-Au8&amp;rank=2">EAP (NCT04081714)</a> was launched in 2019 at the Sean M. Healey &amp; AMG Center for ALS at Massachusetts General Hospital, where the HEALEY ALS platform trial is also being led. A second <a href="https://clinicaltrials.gov/study/NCT05281484?cond=ALS&amp;intr=CNM-Au8&amp;rank=3">EAP (NCT05281484</a>) was launched in 2021, and is available to patients at 16 U.S. sites associated with the Northeast ALS Consortium.
In addition to expanding patient access to the therapy, the EAPs are expected to provide additional safety and efficacy data for regulators to review when deciding on the treatment’s possible approval.
[recommended-reading id=41328]
<h3>Comparing use of CNM-Au8 to natural history, or no treatment</h3>
Clene’s recent update concerned pooled data from the EAPs, through which more than 250 patients have been treated with CNM-Au8 at a daily oral dose of 30 mg.
Survival analyses were conducted to compare outcomes from a total of 220 EAP participants — who had been treated for up to four years — with data from matched untreated ALS patients in either of two databases.
The first was PRO-ACT, a large database containing information from more than 12,000 ALS patients who participated in previous clinical trials. The other was the ALS/MND Natural History Consortium, a study that has collected real-world data from about 1,700 ALS patients.
The results indicated that CNM-Au8 was associated with a significant, 68% decreased risk of death compared with people in PRO-ACT, and a significant, 57% lower risk relative to the ALS/MND Consortium, according to the company.
[quote=&#8221;center&#8221;]The long-term safety and survival data from the CNM-Au8 expanded access programs add to the available data supporting CNM-Au8 moving rapidly to Phase 3 testing in ALS. &#8230; This is one of a few therapies with positive Phase 2 data that must go forward to Phase 3 trials.[/quote]
CNM-Au8 was well tolerated, with no serious adverse events deemed related to treatment. Also, no significant safety findings were identified.
Overall, the findings are consistent with <a href="https://alsnewstoday.com/news/cnm-au8-seen-to-extend-survival-by-more-than-1-5-years-in-als-trial/">previous analyses</a> from the RESCUE and HEALEY-ALS trials, in which treatment with CNM-Au8 <a href="https://alsnewstoday.com/news/long-term-survival-benefit-seen-cnm-au8-healey-als-analyses-trial/">prolonged survival</a> and <a href="https://alsnewstoday.com/news/cnm-au8-delayed-clinical-worsening-als-patients-healey-trial/">delayed clinical worsening</a> in ALS patients.
“The long-term safety and survival data from the CNM-Au8 expanded access programs add to the available data supporting CNM-Au8 moving rapidly to Phase 3 testing in ALS,” said Merit Cudkowicz, MD, chair of neurology and director of the Healey &amp; AMG Center at Mass General Hospital, a principal investigator of the EAP being conducted at Healey &amp; AMG Center, and a professor at Harvard Medical School.
“This is one of a few therapies with positive Phase 2 data that must go forward to Phase 3 trials,&#8221; Cudkowicz added.

CNM-Au8 extends patient survival in 2 ALS compassionate use studies

Early data from Phase 2 programs showing that <a href="https://alsnewstoday.com/cnm-au8/">CNM-Au8</a>, an oral therapy candidate for <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS), induced significant reductions in a nerve damage biomarker but did not meet the criteria for accelerated approval at this time, the U.S. Food and Drug Administration (FDA) concluded.
Despite the FDA’s decision at a recent meeting, <a href="https://clene.com/">Clene Nanomedicine</a>, the therapy’s developer, <a href="https://www.globenewswire.com/news-release/2023/12/21/2799888/0/en/Clene-Reports-Reduction-in-Biomarker-Plasma-Neurofilament-Light-NfL-Levels-and-Improved-Survival-With-CNM-Au8-Treatment-From-HEALEY-ALS-Platform-Trial-Long-Term-Open-Label-Extensio.html">released promising new data</a> from the long-term extension study of the <a href="https://clinicaltrials.gov/ct2/show/NCT04297683">HEALEY ALS platform trial (NCT04297683)</a>.
Results showed CNM-Au8 significantly reduced the blood levels of the nerve damage biomarker neurofilament light chain (NfL) by 16% after about 18 months, decreased the risk of long-term all-cause mortality by 60%, and reduced the risk of clinical worsening in the highest-risk participants.
Clene plans to provide the FDA with supplemental data in the first half of 2024. The data package will include additional long-term clinical evidence and biomarker results, data on CNM-Au8’s mechanism of action and its connection to NfL reduction, as well as the association between lower NfL and improved clinical outcomes, including prolonged survival.
“As we continue to analyze the data from our Phase 2 clinical program, we believe the evidence supports that CNM-Au8 treatment improved survival in people living with ALS,” Benjamin Greenberg, MD, Clene’s head of medical, said in a <a href="https://www.globenewswire.com/news-release/2023/12/21/2799889/0/en/Clene-Provides-Update-on-ALS-Clinical-Development-Meeting-With-FDA.html">company press release</a>. “We are also encouraged that the recently disclosed long-term NfL biomarker decreases are consistent with delayed clinical time-to-event outcomes.”
[recommended-reading id=86465]
<h3>Candidate therapy aims to support health of motor neurons</h3>
CNM-Au8 is an oral liquid suspension of gold nanocrystals that aims to support the health of motor neurons, nerve cells that control voluntary muscle movement which <a href="https://alsnewstoday.com/causes-of-als/">progressively die in people with ALS</a>.
The therapy has been granted orphan drug status by the FDA for ALS, a designation that provides incentives to accelerate CNM-Au8’s clinical development and regulatory review.
In addition to an arm of the HEALEY trial, which simultaneously tested several ALS treatment candidates against a shared placebo group, the therapy is being evaluated in the <a href="https://clinicaltrials.gov/ct2/show/NCT04098406">Phase 2 RESCUE-ALS trial (NCT04098406)</a> and its <a href="https://clinicaltrials.gov/ct2/show/NCT05299658">open-label extension (OLE) study (NCT05299658)</a>. So far, study data show that CNM-Au8 is safe, <a href="https://alsnewstoday.com/news/cnm-au8-seen-to-extend-survival-by-more-than-1-5-years-in-als-trial/">slows ALS progression</a>, and <a href="https://alsnewstoday.com/news/long-term-survival-benefit-seen-cnm-au8-healey-als-analyses-trial/">extends patient survival</a>.
During the initial six months of treatment in the HEALEY trial, CNM-Au8 was associated with a 10% relative reduction in NfL compared with a placebo.
Newly released data from HEALEY’s 12-month OLE study showed the 30 mg dose of CNM-Au8 reduced NfL levels by 16% after 76 weeks, or about 18 months, relative to those initially assigned to a placebo. Similar results were found when data was combined from both doses tested (30 mg and 60 mg).
A long-term survival analysis of HEALEY OLE data compared patients originally assigned CNM-Au8 in the main study compared with those given a placebo. While those on a placebo eventually switched to CNM-Au8 in the OLE, the researchers employed a statistical model that estimated their survival had they remained on a placebo during the OLE period. The data showed a 60% reduction in the risk of all-cause mortality in patients given CNM-Au8 for the entire period.
<h3>Studying relationship between NfL, worsening ALS</h3>
To investigate the relationship between NfL and the incidence of ALS worsening, Clene pooled data from the HEALEY ALS platform and the RESCUE-ALS trials. Participants were classified based on NfL levels before receiving CNM-Au8 (baseline). ALS worsening events included death, needing a breathing or feeding tube, or the initiation of permanent assisted ventilation.
Analyses showed CNM-Au8 significantly delayed these worsening events in the group of patients with the highest baseline NfL levels, indicating greatest nerve cell damage. In these patients, the risk of such events was reduced by 75%.
At the same time, there also were significant extensions in the time to death or the initiation of permanent assisted ventilation, and a reduction in all-cause mortality.
The company plans to launch a Phase 3 study to confirm these findings in 2024.
Meanwhile, the National Institutes of Health (NIH) has recently <a href="https://alsnewstoday.com/news/new-eap-makes-cnm-au8-available-als-patients-outside-trials/">awarded about $45.1 million toward an expanded access program</a> (EAP) of CNM-Au8. Referred to as compassionate use, this program will join two other CNM-Au8 EAP programs to provide CNM-Au8 to U.S. patients who are not eligible for these clinical trials.
“Clene is committed to people living with ALS,” said Rob Etherington, CEO of Clene. “We presently support two ongoing CNM-Au8 compassionate use (expanded access) programs and are shortly commencing a third compassionate use program that is supported by a $45.1M grant from the National Institutes of Health.
“In addition, we anticipate launching the Phase 3 ALS confirmatory study in 2024. Importantly, we also plan to submit new information to the FDA for further discussions on the totality of evidence in order to advance the accelerated development of CNM-Au8 for the treatment of ALS.”
Clene also is testing CNM-Au8 for the treatment of <a href="https://multiplesclerosisnewstoday.com/multiple-sclerosis-overview/">multiple sclerosis</a> and <a href="https://parkinsonsnewstoday.com/what-is-parkinsons-disease/">Parkinson’s disease</a>, two other neurodegenerative disorders.

Biomarker data insufficient to support CNM-Au8’s approval: FDA

The National Institutes of Health (NIH) has awarded about $45.1 million toward an expanded access program (EAP) of <a href="https://alsnewstoday.com/cnm-au8/">CNM-Au8</a>, an oral therapy candidate for <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS).
The EAP, commonly referred to as compassionate use, will make CNM-Au8 available to U.S. patients who aren&#8217;t eligible for clinical trials that are testing the experimental therapy. It will join two other CNM-Au8 EAP programs that have enrolled more than 200 participants.
The programs are expected to provide additional clinical data to support the safety and effectiveness of CNM-Au8, which will be reviewed by regulatory agencies ahead of an approval.
“This EAP study will give ALS patients who don’t meet the criteria to enroll in a clinical trial an opportunity to try CNM-Au8 as a novel investigational therapy,” Jinsy A. Andrews, MD, a professor of neurology at Columbia University, said in a <a href="https://www.globenewswire.com/news-release/2023/10/05/2755532/0/en/National-Institutes-of-Health-Awards-45-1-Million-NINDS-Grant-for-CNM-Au8-Study-in-ALS.html">press release from Clene Nanomedicine</a>, the therapy’s developer.
The program&#8217;s four-year grant comes from the NIH&#8217;s National Institute of Neurological Disorders and Stroke (NINDS), and is supported by the Accelerating Access to Critical Therapies (ACT) for ALS Act, which was signed into law in 2021. The grant was awarded to <a href="https://clene.com/">Clene</a> in collaboration with Columbia University and <a href="https://www.synapticure.com/">Synapticure</a>.
[recommended-reading id=82702]
<h3>Making CNM-Au8 accessible remotely</h3>
The EAP will be led by Andrews, Eric Anderson, MD, vice president of clinical operations and care delivery at Synapticure, and Benjamin Greenberg, MD, head of medical at Clene.
It will enroll patients in all 50 states, including those in remote and rural areas, via Synapticure’s telemedicine neurology clinic and several nationwide clinics.
The program will monitor CNM-Au8&#8217;s safety, its impact on survival and disease progression, and changes in key disease-related biomarkers.
“Programs like this help to advance research and much-needed innovation in ALS,” Andrews said. &#8220;We are truly excited to be a part of this grant with Clene and Columbia and to support people living with ALS by providing access to treatments that could meaningfully impact the course of their disease.&#8221;
She said Synapticure&#8217;s virtual platform will aid in reaching people in remote areas who haven&#8217;t been able to access investigational treatments like CNM-Au8. “We are grateful to NINDS for recognizing how a virtual platform like Synapticure can provide expanded access programs in a remote capacity,&#8221; Andrews said.
<h3>What is CNM-Au8?</h3>
CNM-Au8 is an oral liquid suspension of gold nanoparticles that&#8217;s believed to slow ALS by supporting the energetic needs of nerve cells and other cells of the nervous system. It can also protect them from oxidative stress, a type of cellular stress implicated in the neurodegenerative disease.
It&#8217;s being investigated in the Phase 2 <a href="https://clinicaltrials.gov/ct2/show/NCT04098406">RESCUE-ALS trial (NCT04098406)</a> and its <a href="https://clinicaltrials.gov/ct2/show/NCT05299658">open-label extension (NCT05299658)</a>, as well as in an arm of the <a href="https://clinicaltrials.gov/ct2/show/NCT04297683">HEALEY ALS platform trial (NCT04297683)</a>.
Data from the studies have demonstrated CNM-Au8 is safe and can <a href="https://alsnewstoday.com/news/cnm-au8-seen-to-extend-survival-by-more-than-1-5-years-in-als-trial/">slow disease progression</a> and <a href="https://alsnewstoday.com/news/long-term-survival-benefit-seen-cnm-au8-healey-als-analyses-trial/">extend survival</a> in patients.
“Clene has demonstrated evidence of consistent safety and improved survival for CNM-Au8 across a broad ALS population in two independent Phase 2 trials and an ongoing EAP with up to 3.8 years of follow-up,” Greenberg said. “This new EAP provides access to CNM-Au8 for more people living with ALS and enables the collection of survival, safety, and biomarker data in a population not studied in clinical trials. These data can help provide confirmatory support for the existing trial data Clene has gathered in its clinical trials.&#8221;

New EAP will make CNM-Au8 available outside of trials

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.
[recommended-reading id=78394]
<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

Treatment with <a href="https://alsnewstoday.com/cnm-au8/">CNM-Au8</a> was found to significantly delay disease progression and prolong survival, by more than 1.5 years, among adults with early-stage <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS) in the RESCUE-ALS trial and its open-label extension phase.
That&#8217;s according to two different statistical analyses, which overall showed that patients who received CNM-Au8 had a 70% lower risk of death over two years of follow-up compared with those never given the medication.
Indeed, the new analyses revealed a &#8220;19.3 month significant survival difference for CNM-Au8 treated participants versus [those on a] placebo,&#8221; <a href="https://clene.com/">Clene Nanomedicine</a>, the company developing CNM-Au8, stated in a <a href="https://www.globenewswire.com/news-release/2023/08/29/2733238/0/en/Clene-Reports-Significantly-Improved-Survival-Benefit-of-19-3-Months-and-Significantly-Delayed-Clinical-Worsening-in-Rescue-Als-Open-Label-Extension-Two-Year-Follow-Up.html">press release</a>.
“The data that continues to be received from the RESCUE-ALS open label extension study is truly impressive, and now shows consistently significant decreased risk of death greater than 70% using two different long-term analysis models,” said Matthew Kiernan, PhD, of the University of Sydney, one of the trial&#8217;s clinical advisors.
“The survival benefit across treatment arms is linked to less worsening of disease, as experienced by ALS patients. At the same time, the further safety data confirms that CNM-Au8 is well tolerated in ALS patients,” Kiernan added.
[recommended-reading id=84096]
<h3>Main trial of CNM-Au8 failed to meet primary, secondary goals</h3>
The oral therapy is a suspension of gold nanoparticles that&#8217;s intended to slow ALS progression by preventing the death of the motor nerve cells that are progressively lost in the disease.
CNM-Au8 is believed to promote nerve cell survival by boosting energy production and protecting against a type of cellular damage, called oxidative stress, that&#8217;s implicated in ALS .
The Phase 2 <a href="https://clinicaltrials.gov/ct2/show/NCT04098406">RESCUE-ALS trial (NCT04098406)</a>, sponsored by Clene and launched in late 2019, enrolled 45 adults with early ALS at two sites in Australia. All had developed their first symptoms of the progressive disorder in the prior two years.
The participants were randomly assigned to receive CNM-Au8, at a dose of 30 mg, or a placebo, given as a liquid suspension once daily for 36 weeks, or about eight months. The therapy was given in addition to <a href="https://alsnewstoday.com/als-treatment/">standard ALS medications</a>.
Following the main trial, most participants (90%) entered into an <a href="https://clinicaltrials.gov/ct2/show/NCT05299658">open-label extension (NCT05299658)</a>, in which all would be given CNM-Au8 for up to 120 weeks, or more than two years.
The main trial had <a href="https://alsnewstoday.com/news/cnm-au8-failed-primary-rescue-als-goals-top-line-trial-data/">failed to meet its primary and key secondary goals</a> of improving motor nerve cell health and slowing lung function declines after 36 weeks.
However, additional analyses spanning the trial and its extension have indicated a <a href="https://alsnewstoday.com/news/early-cnm-au8-treatment-als-continues-show-survival-benefits/">survival benefit</a> and <a href="https://alsnewstoday.com/news/slower-progression-experimental-als-treatment-cnm-au8/">slower disease progression</a> among patients who started the therapy eight months earlier relative to those who switched from the placebo in the extension phase.
[recommended-reading id=84549]
<h3>Survival benefits with CNM-Au8 still being seen in extension trial</h3>
Now, Clene has reported that the survival benefits of CNM-Au8 are still being observed as of July 2023 — after two years in the extension trial.
Specifically, patients who started CNM-Au8 eight months earlier had a median survival of 34.2 months, or almost three years, compared with 24.1 months, or about two years, among those who switched from placebo. That&#8217;s a survival benefit of 10.1 months, and it amounts to a 46% lower risk of death among those originally assigned to CNM-Au8.
Investigators also conducted another survival analysis wherein the data were adjusted to subtract the potential survival benefits received by those who started on a placebo and then switched to CNM-Au8.
Essentially, the analysis estimated survival in this group if the patients had remained on a placebo and never switched over. That survival was determined to be 14.9 months, or about 1.2 years.
Here, the survival benefits of those always on CNM-Au8 were even more pronounced, with patients living about 19.3 months longer relative to those on a placebo. This was associated with a 75% lower risk of death in participants on continuous CNM-Au8.
[quote=&#8221;center&#8221;]A median survival improvement of 19.3 months provides people living with ALS, their families, and caregivers more time that is so invaluable, and adds to the totality of data we are seeing in our ALS clinical program.[/quote]
The researchers then compared the survival of individuals treated with CNM-Au8 with historical placebo-treated patients — controls whose data were contained in the PRO-ACT ALS patient database. In that analysis, treatment with CNM-Aug was associated with a 70% lower risk of death.
Patients initially assigned the experimental therapy in the main trial also were found to be at a 52% lower risk of clinical worsening compared with those who started treatment eight months later. Clinical worsening was defined as the occurrence of one of several outcomes: death, breathing tube placement, assisted ventilation, or feeding tube placement.
Among open-label participants treated with CNM-Au8, 42% are still alive up to 3.5 years after their enrollment in RESCUE-ALS — and up to 6.6 years after their ALS symptom onset — according to Benjamin Greenberg, MD, head of medical at Clene.
Greenberg called this finding &#8220;a profoundly meaningful milestone for people living with this devastating disease.&#8221;
“A median survival improvement of 19.3 months provides people living with ALS, their families, and caregivers more time that is so invaluable, and adds to the totality of data we are seeing in our ALS clinical program,” Greenberg said.
[recommended-reading id=83732]
<h3>CNM-Au8 also shows benefit in ALS platform trial</h3>
Similar findings also were observed in the CNM-Au8 arm of <a href="https://clinicaltrials.gov/ct2/show/NCT04297683">HEALEY ALS (NCT04297683)</a>, a platform trial that is investigating multiple ALS therapies simultaneously as a way to reduce costs and accelerate treatment development.
In that platform trial arm, treatment with 30 mg CNM-Au8 for six months lowered the risk of death by <a href="https://alsnewstoday.com/news/cnm-au8-found-lower-risk-death-als-healey-platform-trial/">more than 90%</a>. Moreover, <a href="https://alsnewstoday.com/news/cnm-au8-delayed-clinical-worsening-als-patients-healey-trial/">significant reductions also were observed</a> in the risk of needing a feeding tube, assisted ventilatory support, or being hospitalized.
Additionally, in more than 475 collective years of CNM-Au8 exposure in patients with several neurodegenerative disorders — 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> — no safety signals have been identified, according to researchers. Most reported side effects have been mild to moderate in severity, and temporary.
Side effects reported in RESCUE-ALS include nausea, bruising, abdominal discomfort, and aspiration pneumonia, or inflammation caused by food or liquids inhaled into the airways.
Clene has reported plans to launch a Phase 3 trial of CNM-Au8 called RESTORE-ALS. Should results be positive, the data may support regulatory applications for the therapy&#8217;s approval.

CNM-Au8 seen to extend survival by more than 1.5 years in ALS trial

<a href="https://alsnewstoday.com/cnm-au8/">CNM-Au8</a> extended long-term survival and slowed disease progression in adults with early stage <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS) compared with a placebo, according to final data from the RESCUE-ALS clinical trial and one-year findings in its open-label extension (OLE).
Patients treated initially with CNM-Au8 in the main trial experienced significantly slower progression than those who switched to CNM-Au8 from a placebo eight months later in the OLE.
“Results from RESCUE-ALS study were important because they provided the first insights about the clinical benefits of CNM-Au8 in ALS patients and the duration of treatment required to detect them,” Steve Vucic, PhD, a neurology professor at the University of Sydney and a RESCUE-ALS co-investigator, said in a <a href="https://invest.clene.com/news-releases/news-release-details/clene-announces-publication-phase-2-cnm-au8r-clinical-data">press release</a>.
Details are in the study, &#8220;<a href="https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(23)00213-4/fulltext">Efficacy and safety of CNM-Au8 in amyotrophic lateral sclerosis (RESCUE-ALS study): a phase 2, randomised, double-blind, placebo-controlled trial and open label extension</a>,&#8221; published in the journal <a href="https://www.thelancet.com/journals/eclinm/home">eClinicalMedicine</a>. The study was funded by a grant from <a href="https://fightmnd.org.au/">FightMND</a>, as well as <a href="https://clene.com/">Clene Nanomedicine</a>, the therapy&#8217;s developer.
[recommended-reading id=85452]
<h3>CNM-Au8 failed at the trial&#8217;s main and key secondary goals</h3>
<a href="https://alsnewstoday.com/causes-of-als/">ALS is marked</a> by the progressive loss of motor neurons, the nerve cells in the brain and spinal cord that facilitate movement, breathing, speaking, and swallowing.
CNM-Au8 is a nanocrystalline gold suspension that aims to prevent motor neuron death and slow <a href="https://alsnewstoday.com/living-with-als-2/">ALS progression</a>. It is thought to promote nerve cell function and survival by increasing energy production while protecting these cells from oxidative stress, a type of cellular damage associated with ALS.
The <a href="https://clinicaltrials.gov/ct2/show/NCT04098406">Phase 2 RESCUE-ALS trial (NCT04098406)</a> enrolled 45 adults (19 women, 26 men) with early ALS at its two sites in Australia. Participants were randomly assigned to a liquid suspension containing 30 mg of CNM-Au8 or a placebo, given each morning for 36 weeks (about eight months), plus standard care.
Most patients (91%) were on riluzole (sold as <a href="https://alsnewstoday.com/rilutek-riluzole-for-als/">Rilutek</a>, generics available), and 2% received <a href="https://alsnewstoday.com/radicava-edaravone-for-als/">Radicava</a> (edaravone) as their stable standard-of-care treatment.
After completing the main trial, most patients (90%) entered the trial&#8217;s <a href="https://clinicaltrials.gov/ct2/show/NCT05299658">open-label extension (NCT05299658)</a>, in which all received CNM-Au8 once daily. It is due to conclude at year&#8217;s end.
As previously reported, data spanning both studies indicated that early treatment with CNM-Au8 showed a potential to <a href="https://alsnewstoday.com/news/slower-progression-experimental-als-treatment-cnm-au8/">slow disease progression</a> and <a href="https://alsnewstoday.com/news/early-cnm-au8-treatment-als-continues-show-survival-benefits/">reduce the risk of death</a>.
Researchers now report full RESCUE-ALS data and OLE findings through mid-January 2022.
The trial failed to meet its main goal of improving Motor Unit Number Index (MUNIX) scores after 36 weeks, which measured motor neurons&#8217; number, function, and health. The mean MUNIX change was similar between CNM-Au8 and placebo (−31.8% vs. –39.6%).
However, researchers noted that people with <a href="https://alsnewstoday.com/forms-of-als/#Clinical_onset">bulbar-onset ALS</a> — a disease form marked by initial symptoms of muscle weakness in the head and neck, affecting 27% of patients in the trial — did not experience any decline in MUNIX scores regardless of treatment, which could account for the lack of differences between groups.
In a key secondary measure, the treatment also failed to slow lung function decline, even after accounting for potential confounding factors.
<h3>Exploratory analyses support CNM-Au8 slowing disease progression</h3>
Yet, exploratory analyses showed that CNM-Au8 treatment slowed ALS disease progression by 55% compared with a placebo through week 36. Disease progression was defined as the first occurrence of breathing tube insertion, the need for noninvasive breathing support, feeding tube placement, or death. At the end of the main trial, more CNM-Au8-treated patients went without such events relative to those on a placebo (78% vs. 23%).
Likewise, fewer patients on CNM-Au8 experienced a six-point or greater decline in ALS Functional Rating Scale-Revised (ALSFRS-R) scores, indicating more difficulty in daily life functions, than those given a placebo (18% vs. 48%).
Treatment also slowed a worsening in quality of life, as assessed by the ALS Specific Quality of Life–Short Form (ALSSQOL-S) questionnaire.
Deaths through week 36 also were less frequent with CNM-Au8&#8217;s use compared with a placebo (4% vs. 9%). This trend became more pronounced during the OLE, with a statistically significant 60% reduction in all-cause mortality over one year of follow-up. Overall, seven patients on continuous CNM-Au8 and 15 of those originally assigned a placebo have died.
&#8220;These preliminary survival results should similarly be evaluated prospectively in an appropriately powered Phase 3 study,&#8221; the researchers wrote.
After 48 weeks, early treatment with CNM-Au8 continued to result in a significantly lower rate of disease progression compared with an eight-month delayed treatment start — a 2.6 point difference in ALSFRS-R scores.
Those findings were somewhat expected, because placebo patients would not yet have achieved effective bloodstream concentrations of the therapy. After offsetting the OLE analysis to account for the slow absorption of CNM-Au8, significant differences in ALSFRS-R decline still were seen in patients who started the treatment early. These patients declined by 0.397 fewer points per month between weeks 60 and 120 than those who started treatment at week 36 with OLE entry.
This finding may suggest that &#8220;participants originally randomised to placebo had much worse decline overall and could not overcome the initial decline of [ALSFRS-R] &#8230; compared to participants originally randomised to active treatment,&#8221; the researchers wrote.
Fewer ALS progression events also were recorded in OLE patients on continuous, 120-week use of CNM-Au8 compared with the initial placebo group (46.2% vs. 15.3%). The researchers noted that these events may be underestimated, because some placebo-group patients who did not enter the OLE died within months of finishing the main trial.
“The treatment effect demonstrated a clear survival signal associated with CNM-Au8 treatment and evidence for delayed clinical worsening morbidity events such as tracheostomy and initiation of feeding tube during the double-blind placebo-controlled period,&#8221; Vucic said. &#8220;Additional functional benefits such as decreased worsening of ALSFRS-R scores are emerging later through the long-term open-label extension.”
&#8220;The long-term OLE data through a minimum of 52-weeks of CNM-Au8 treatment (for participants originally randomised to placebo) provided additional signals of potential CNM-Au8 treatment benefit,&#8221; the researchers wrote.
<h3>RESCUE-ALS results in line with findings in CNM-Au8 arm of HEALEY study</h3>
CNM-Au8 was well tolerated, with treatment-emergent adverse events (TEAE) and serious adverse events balanced between CNM-Au8 and placebo groups. The most common events related to CNM-Au8 treatment were nausea, bruising, abdominal discomfort, and aspiration pneumonia (airway inflammation caused by inhaled liquid or food). Standard lab tests did not show any clinically abnormal findings.
Survival data also aligned with top-line results from the <a href="https://clinicaltrials.gov/ct2/show/NCT04414345">CNM-Au8 arm (NCT04414345)</a> of the <a href="https://clinicaltrials.gov/ct2/show/NCT04297683?term=HEALEY+ALS&amp;draw=2&amp;rank=1">HEALEY platform trial (NCT04297683)</a>. Although the study failed to meet its primary outcome of slowing disease progression, six months of treatment <a href="https://alsnewstoday.com/news/cnm-au8-found-lower-risk-death-als-healey-platform-trial/">reduced the risk of death</a> by about 90%.
Plans for a global Phase 3 trial of CNM-Au8, called RESTORE-ALS, are underway. Pending positive results, data from this trial may support regulatory requests to approve CNM-Au8.
The company also plans to discuss next steps for its ALS program with the U.S. Food and Drug Administration (FDA) later this year.
“We are pleased that CNM-Au8 results in RESCUE-ALS were concordant with the larger Phase 2b HEALEY ALS Platform Trial,” said Ben Greenberg, MD, head of medical at Clene. “We plan to report long-term follow-up data from this program later this year and meet with the FDA in the third quarter to identify next steps for our ALS program.”

CNM-Au8 slows disease progression and extends life, RESCUE-ALS finds

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.
[recommended-reading id=79748]
<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.

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

<a href="https://alsnewstoday.com/what-is-als/">Amyotrophic lateral sclerosis</a> (ALS) patients treated earlier with <a href="https://alsnewstoday.com/cnm-au8/">CNM-Au8</a> in a clinical trial experienced a significantly slower disease progression than those who started treatment nine months later.
These latest findings 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 (OLE) study (NCT05299658)</a> add to earlier reports that people on this gold nanocrystal therapy for longer periods saw a significant survival benefit.
&#8220;The totality of data generated from the CNM-Au8 ALS clinical program and the long-term patient benefits are highly encouraging,&#8221; Steve Vucic, PhD, a trial co-investigator, said in a <a href="https://www.globenewswire.com/news-release/2023/03/06/2620932/0/en/New-Data-Show-CNM-Au8-Preserved-ALS-Patient-Function-and-Slowed-Disease-Progression-in-the-Open-Label-Extension-of-the-Phase-2-RESCUE-ALS-Trial.html">press release</a> from CNM-Au8&#8217;s developer, <a href="https://clene.com/" rel="nofollow">Clene Nanomedicine</a>.
&#8220;It is extraordinarily notable that a nine-month difference in treatment initiation &#8230; substantially preserved long-term function,&#8221; added Vucic, a professor holding the Northcott chair of neurology at the University of Sydney. &#8220;With its favorable tolerability profile and ability to be used alone or in combination with other ALS therapies, early treatment with CNM-Au8 may play an essential role in the treatment of ALS.&#8221;
[recommended-reading id=82449]
<h3>Analyses of treatment vs. placebo groups well into open-label extension trial</h3>
CNM-Au8 is an oral liquid suspension containing gold nanocrystals designed to support nerve cells&#8217; energetic needs and to protect them from oxidative stress, a type of cellular damage implicated in ALS. It aims to prevent nerve cell death and slow ALS disease progression.
The RESCUE-ALS trial enrolled 45 adults with early ALS, meaning symptoms first appearing over the previous two years, who were randomized to a liquid suspension containing 30 mg of CNM-Au8 or a placebo, once daily for 36 weeks or about nine months.
The trial <a href="https://alsnewstoday.com/news/cnm-au8-failed-primary-rescue-als-goals-top-line-trial-data/">failed to meet its main goal</a> of preventing the loss of motor neurons, specialized cells that are progressively damaged in ALS, as well as a key secondary goal of slowing lung function decline.
However, additional analyses supported treatment <a href="https://alsnewstoday.com/news/mda-2022-cnm-au8-may-slow-als-progression-reduce-mortality-risk/">slowing clinical worsening</a>, with fewer patients on CNM-Au8 experiencing a six-point decline in ALS Functional Rating Scale-Revised (ALSFRS-R) scores compared with those given a placebo (60% vs. 80%).
CNM-Au8&#8217;s use also significantly improved quality of life and resulted in a 37% reduction in the risk of disease progression, defined as death, or the need for breathing support or feeding tube placement.
Thirty-six patients, 90%, chose to enter the trial&#8217;s open-label extension, in which all are receiving CNM-Au8 once daily.
Previous analyses indicated that patients initially assigned to CNM-Au8 in the main RESCUE-ALS trial had a<a href="https://alsnewstoday.com/news/early-cnm-au8-treatment-als-continues-show-survival-benefits/"> 70% lower risk of death</a> than those starting treatment nine months later in the OLE.
Newly released findings cover patients treated for up to 120 weeks (about 2.3 years) across the main trial and its OLE, with a data cut-off date of July 14. These findings also were shared in a recent <a href="https://invest.clene.com/presentations/investor-presentation" rel="nofollow">investor presentation</a>.
In line with main trial analyses, CNM-Au8 significantly slowed ALSFRS-R score declines, indicating preserved function, among patients on long-term treatment compared with those initially given a placebo.
The slower decline was observed during first 48 weeks of OLE treatment, a somewhat expected finding as placebo group patients would not yet have achieved effective bloodstream concentrations of the therapy.
<h3>Good safety with experimental ALS treatment reported</h3>
What&#8217;s notable is slower ALSFRS-R declines in patients on continuous CNM-Au8 use, relative to later starters, across weeks 60 to 120, when all OLE patients had effective blood concentrations of CNM-Au8, according to Clene.
Patients starting the therapy nine months later, on average, declined by six ALSFRS-R points more than those given CNM-Au8 from the main trial&#8217;s start.
Consistently treated patients also showed significant delays in the time to clinical worsening, including death, or a need for ventilation support or a feeding tube. Their risk for any of these events was more than 50% lower than the later treatment group.
CNM-Au8 was well tolerated with no long-term safety concerns, the company noted.
RESCUE-ALS survival data also were consistent with top-line data from the <a href="https://clinicaltrials.gov/ct2/show/NCT04414345">CNM-Au8 arm (NCT04414345)</a> of the <a href="https://clinicaltrials.gov/ct2/show/NCT04297683?term=HEALEY+ALS&amp;draw=2&amp;rank=1">HEALEY platform trial (NCT04297683)</a>, which found that a 30 mg dose <a href="https://alsnewstoday.com/news/cnm-au8-found-lower-risk-death-als-healey-platform-trial/">lowered the risk of death</a> by about 90% after some six months of treatment.
This trial also failed to met its primary goal of slowing disease progression, as measured in ALSFRS-R score changes.
“The open-label data at 48 weeks and through 120 weeks from randomization suggests that CNM-Au8 has the ability to meaningfully improve patient daily functional status over longer periods of time, together with sustained treatment effects on ALS disease progression and survival,” said Matthew Kiernan, PhD, a RESCUE-ALS trial investigator and University of Sydney professor holding the Bushell chair of neurology.
Recent analyses also confirm the therapy&#8217;s “excellent safety profile,” Kiernan added.

Tag: CNM-Au8