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Treatment with <a href="https://alsnewstoday.com/ionis-sod1-rx-biib067/">Qalsody</a> (tofersen) in the real world slowed disease progression in people with <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS) caused by SOD1 mutations, a small study reports.
It also stabilized patients&#8217; quality of life and lowered levels of nerve damage-related biomarkers, which is consistent with clinical trial data that supported its approval.
&#8220;Treatment with [Qalsody] was shown to be an effective therapeutic approach,&#8221; the researchers wrote in “<a href="https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(24)00074-9/fulltext">Effects of tofersen treatment in patients with SOD1-ALS in a “real-world” setting – a 12-month multicenter cohort study from the German early access program</a>,” which was published in eClinicalMedicine.
Qalsody was <a href="https://alsnewstoday.com/news/fda-approves-tofersen-now-qalsody-treatment-adults-sod1-als/">conditionally approved in the U.S.</a> in 2023 for ALS patients who harbor mutations in the SOD1 gene, which are associated with up to 20% of <a href="https://alsnewstoday.com/forms-of-als/familial-als/">familial ALS</a> cases and about 2% of <a href="https://alsnewstoday.com/forms-of-als/sporadic-als/">sporadic</a> cases. Last month, a committee of the European Medicines Agency (EMA) <a href="https://alsnewstoday.com/news/committee-favors-eu-approval-qalsody-1st-treatment-sod1-als/">recommended</a> that Qalsody be approved in the European Union under exceptional circumstances.
The therapy, which is administered intrathecally, that is, directly into the spinal canal, suppresses the production of mutant SOD1 protein to slow disease progression and extend survival.
Its applications in the U.S. and Europe were based on data from the three-part <a href="https://www.clinicaltrials.gov/ct2/show/NCT02623699">Phase 1/2/3 VALOR trial (NCT02623699)</a> and its ongoing <a href="https://clinicaltrials.gov/ct2/show/NCT03070119">open-label extension study (NCT03070119)</a>, where Qalsody slowed disease progression, extended survival, and lowered neurofilament light chain (NfL), a marker of nerve damage.
Early access programs (EAPs) were launched in a number of countries based on the findings to provide Qalsody to SOD1-ALS patients outside of clinical trials before its regulatory approval.
[recommended-reading id=90434]
<h3>Qalsody in real-world settings</h3>
Here, researchers report on data from 24 SOD1-ALS patients who received Qalsody under an EAP in Germany between March 2022 and April 2023.
The patients received a median of eight Qalsody doses over a median observation period of six months. Of them, half were women and 58.3% had a family history of the disease.
The median rate of progression, as assessed using the ALS Functional Rating Scale Revised (ALSFRS-R), was slower with Qalsody than at the start of the study, or its baseline. Patients lost a median of 0.11 ALSFRS-R points a month after starting treatment compared with 0.41 monthly points before starting Qalsody.
Seventeen patients had a slower progression rate with treatment compared with the baseline and six had a faster progression.
Those with a faster progression had a shorter disease duration at the time they started Qalsody and higher levels of nerve damage biomarkers, including NfL and phosphorylated neurofilament heavy chain (pNfH). These patients&#8217; observation period was also shorter, “implying that they have received fewer doses of Qalsody,” the researchers wrote. No changes in muscle strength were seen in nine patients with available data.
Self-reported quality of life showed stable results among eight evaluable patients. The participants generally indicated severe problems with mobility and self-care, and slight to moderate levels of pain, discomfort, anxiety, and depression.
Other measures deteriorated from moderate to severe during treatment, including the ability to perform work, study, housework, and family or leisure activities. No changes were observed when the patients were asked to indicate their current state of health on a scale from 0 to 100, however.
In contrast, blood levels of NfL and spinal fluid levels of pNFH significantly dropped with treatment, indicating reduced nerve cell damage.
&#8220;Based on preexisting evidence, treatment with tofersen in SOD1-ALS leads to a reduction in neurofilament levels (NfL),&#8221; the scientists wrote. &#8220;This study provides evidence that these findings can be extended to pNfH in CSF.&#8221;
Two potentially treatment-related serious side effects were reported. One patient was diagnosed with autoimmune-related inflammation of the spinal cord, or myeloradiculitis, and another had short-term weakness in the lower limbs. Both discontinued treatment. No other drug-related side effects were reported, other than those related to the therapy&#8217;s administration into the spinal canal, such as lower back pain, headache, and pain, weakness, numbness, and tingling in the lower limbs.
“The findings of this study suggest that treatment of SOD1-ALS patients with intrathecal administration of [Qalsody] is an effective therapeutic approach,” the researchers wrote.

Qalsody slows ALS disease progression in real-world settings

<a href="https://seelostherapeutics.com/sls-005-trehalose/">SLS-005</a> did not significantly slow <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS) progression compared with a placebo in the HEALEY platform trial, according to top-line data showing that the experimental therapy did not ease functional declines nor extend patient survival.
The therapy, developed by <a href="https://seelostherapeutics.com/">Seelos Therapeutics</a>, also failed to slow declines in muscle strength and lung function, which, overall, means the trial failed to meet its primary and key secondary measures.
“Though we did not achieve success with this trial, we remain committed to using the data to advance ALS science, and our experience with the trial to understand ALS,&#8221; Merit Cudkowicz, MD, principal investigator and sponsor of the HEALEY ALS Platform Trial, said in a <a href="https://www.massgeneral.org/neurology/als/news/healeyamg-announces-platform-trial-update">press release</a>.
“We are thankful to the many people who participated in this study. We will learn from these results and continue to use this data to inform future advances in ALS trial design,” added Cudkowicz, who is also director of the Sean M. Healey &amp; AMG Center for ALS, chief of the Department of Neurology at Massachusetts General Hospital (MGH), and the Julieanne Dorn Professor of Neurology at Harvard Medical School.
[recommended-reading id=83732]
<h3>SLS-005 aims to slow ALS progression by breaking down toxic protein clumps</h3>
SLS-005 contains trehalose, a natural sugar molecule that promotes autophagy, which is a cellular recycling process that helps break down old and faulty proteins. In so doing, it prevents them from toxically accumulating in cells.
The therapy was designed to slow ALS progression by entering the brain and breaking down these toxic protein clumps. Such clumps, or aggregates, contribute to nerve cell death in the neurodegenerative disease.
SLS-005 was assessed in the <a href="https://clinicaltrials.gov/ct2/show/NCT04297683?term=HEALEY+ALS&amp;draw=2&amp;rank=1">HEALEY platform trial (NCT04297683)</a> — a novel approach to drug testing in which multiple ALS therapy candidates are investigated simultaneously against a shared placebo group. Dubbed a perpetual trial, HEALEY continues to <a href="https://clinicaltrials.gov/ct2/show/NCT04297683?term=HEALEY+ALS&amp;draw=2&amp;rank=1#contacts">enroll adults</a> with ALS whose first symptoms occurred within the last three years.
The trial is ongoing at dozens of U.S. sites. Once a participant is deemed eligible through the trial’s master protocol, he or she can be randomly assigned to any active treatment arm.
The <a href="https://clinicaltrials.gov/ct2/show/NCT05136885">SLS-005 arm (NCT05136885)</a> enrolled 161 patients: Among them, 120 received weekly SLS-005 infusions into the bloodstream, and the rest, a placebo.
The participants also could continue to use a stable regimen of <a href="https://alsnewstoday.com/approved-treatments-for-als/">approved ALS therapies</a>, consisting of <a href="https://alsnewstoday.com/radicava-edaravone-for-als/">Radicava</a> (edaravone) or riluzole (e.g., Rilutek, Tiglutik, Exservan). <a href="https://alsnewstoday.com/amx0035/">Relyvrio</a> (sodium phenylbutyrate and taurursodiol) was approved about eight months after the SLS-005 trial arm began enrollment, and some participants also ended up receiving that newly approved medication along with their assigned treatment.
As with all arms of the platform trial, the main goal was to evaluate whether SLS-005 could significantly slow disease progression relative to the placebo over 24 weeks, or about six months.
Progression was assessed with the ALS Functional Rating Scale-Revised (ALSFRS-R), which measures a person&#8217;s ability to perform activities of daily living, such as turning in bed, gripping a pen, climbing stairs, speaking, and breathing.
[recommended-reading id=41326]
<h3>Monthly declines in ALSFRS-R scores seen in SLS-005, placebo groups</h3>
Seelos now has reported that the trial’s goal was not met, with patients in the SLS-005 arm and the shared placebo group seeing similar monthly declines in ALSFRS-R scores.
In an analysis accounting for functional declines and mortality, SLS-005 was associated with a 13% delay in disease progression or death; however, these differences failed to reach statistical significance. Similarly to the primary goal, other key secondary endpoints, such as muscle strength and respiratory function, also were not met.
[quote=&#8221;center&#8221;]Even though the trial results were negative, participants&#8217; involvement in the trial contributed greatly to ALS research by providing substantial clinical and biomarker data that will help us better understand ALS disease mechanisms and the role of the cellular catalysts in people living with ALS and may help unlock keys to the next ALS treatment.[/quote]
“We would like to extend our sincere gratitude to participants in the trehalose regimen who committed their invaluable time and energy in the trial as well as the NEALS investigators and study staff for their dedicated effort and expertise,&#8221; said Shafeeq Ladha, MD, Barrow Neurological Institute and co-lead investigator of the trehalose regimen.
“Even though the trial results were negative, participants&#8217; involvement in the trial contributed greatly to ALS research by providing substantial clinical and biomarker data that will help us better understand ALS disease mechanisms and the role of the cellular catalysts in people living with ALS and may help unlock keys to the next ALS treatment,” Ladha added.
Seelos, however, shared some data suggesting that SLS-005 may have benefited a subset of patients who did not simultaneously receive Relyvrio while in the trial. Relyvrio was <a class="c-link" href="https://alsnewstoday.com/news/relyvrio-amx0035-approved-us-als-treatment/" target="_blank" rel="noopener noreferrer" data-stringify-link="https://alsnewstoday.com/news/relyvrio-amx0035-approved-us-als-treatment/" data-sk="tooltip_parent">approved in the U.S.</a> in 2022, but now is being withdrawn after it failed to show efficacy in a clinical trial.
During the SLS-005 trial, while it wasn&#8217;t initially planned for, some participants ultimately started using Relvvrio. Seelos believes this mid-trial addition could confound the results, and noted that, by removing those individuals, the analysis is cleaner and more in line with how the data appeared originally.
For its part, SLS-005 was generally well tolerated. More deaths occurred in the SLS-005 group, but none were considered related to treatment. Seelos notes that it plans to run additional analyses, including those related to biomarkers and patient subgroups, as the data become available.
The company now is also planning to meet with the U.S. Food and Drug Administration (FDA) to discuss the next steps for SLS-005&#8217;s development.
“We believe the observed signal and success probability is competitive to other recently FDA-approved therapies for ALS,&#8221; Raj Mehra, PhD, chairman and CEO of Seelos said in a <a href="https://www.prnewswire.com/news-releases/seelos-therapeutics-provides-update-on-top-line-results-from-its-amyotrophic-lateral-sclerosis-als-study-with-sls-005-iv-trehalose-302092918.html">company press release</a>. &#8220;We plan to request a meeting with the FDA to discuss potential next steps for the program.”

Infusion therapy SLS-005 fails to slow ALS progression in trial

Daily treatment with <a href="https://www.pharmaust.com/monepantel-for-motor-neurone-disease/">monepantel</a> — a drug widely used in veterinary medicine — was shown to reduce the rate of disease progression by as much as 58% in people with <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS) or motor neuron disease (MND), according to top-line data from a Phase 1 trial.
The oral therapy also was found to be generally safe and well tolerated.
The data comes from the completed <a href="https://clinicaltrials.gov/study/NCT04894240">MEND trial (NCT04894240)</a>, which assessed the safety, tolerability, and pharmacological properties of monepantel in 12 adults with ALS or MND at two sites in Australia. MEND also sought to determine any preliminary signs of efficacy for the treatment candidate.
Researchers already have selected the optimal dose for further testing, which will be assessed in a Phase 2/3 clinical study expected to start in the third quarter of this year. That trial may support accelerated U.S. Food and Drug Administration approval in 2026, according to the therapy&#8217;s developer <a href="https://www.pharmaust.com/">PharmAust</a>.
&#8220;This study has shown oral monepantel to be safe and well tolerated by people with MND,&#8221; Susan Mathers, associate professor at Monash University and a principal investigator of the trial, said in a <a href="https://www.prnewswire.com/news-releases/pharmaust-announces-positive-phase-1-mend-study-top-line-results-in-mnd--als-302074155.html">company press release</a>. &#8220;Given the promising findings on preliminary efficacy markers, I look forward to progressing a Phase 2 study as soon as possible.&#8221;
Monepantel is widely used in veterinary medicine as a deworming agent. It has also been reported as a potent <a href="https://www.pharmaust.com/therapeutic-pipeline/">inhibitor of the mTOR signaling pathway</a>, which plays a central role in cell growth and proliferation, as well as autophagy, a process by which cells recycle abnormal or defective components or molecules.
PharmAust scientists believe that by activating this pathway, the medication may help to clear the misfolded proteins that accumulate to toxic levels and contribute to disease progression in virtually all ALS patients.
&#8220;The release of the top-line Phase 1 MEND study results is an exciting milestone for PharmAust as we take a significant step towards helping people diagnosed with this rare and incurable disease,” said Michael Thurn, PhD, CEO at PharmAust.
[recommended-reading id=88913]
<h3>Dosing determined during study&#8217;s extension part</h3>
The MEND trial included two groups of six participants each, all ages 18 to 75. One group received the medication at a low dose, of 2 mg/kg and 6 mg/kg, while the other was given a high dose — 4 mg/kg and 10 mg/kg. All doses were given as oral tablets once daily for 28 days. Dose escalations could then be offered every 28 days, based on recommendations from a safety management committee.
An <a href="https://www.pharmaust.com/additional-phase-1-data-suggest-mpl-may-inhibit-mnd/">interim trial analysis</a> showed that blood levels of a nerve cell damage biomarker called neurofilament light chain remained stable in 11 of the 12 participants for as long as 8.7 months.
The newly reported data comes after all patients received the therapy for 10 to 16 months. After completing the main trial, all continued to receive monepantel in an <a href="https://clinicaltrials.gov/study/NCT06177431">open-label extension study (NCT06177431)</a> for up to one year. In an open-label trial, both researchers and participants know the exact medication and dosage being given.
In this part, monepantel was given at a daily dose of 10 mg/kg, which &#8220;is estimated to produce the most robust mTOR inhibition while still being well tolerated,&#8221; the researchers wrote.
The treatment was deemed generally safe and well tolerated. While 56 treatment-emergent adverse events were reported, only three mild events were considered potentially related to treatment. No patient died during the study.
Regarding efficacy, no significant differences in disease severity, as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R), were observed from before treatment to the end of the trial, indicating that monepantel slowed the rate of disease progression in these patients.
[recommended-reading id=89867]
<h3>ALS trial comparison confirms slowing of disease progression</h3>
A comparison of data from study participants versus matched controls from previous ALS clinical studies showed that both the low and high doses of monepantel significantly lowered the rate of disease progression. The controls came from the PRO-ACT database, a large repository of data from people who participated in ALS clinical trials and observational studies.
Monepantel-treated patients had a monthly ALSFRS-R of 0.74 points, representing a 39% slowing in disease progression compared with the matched controls. The effect was more evident in the high dose group, where the rate of decline was 0.6 points per month, or 58% slower than the control group.
&#8220;I feel that the monepantel may have slowed my neurological deterioration,&#8221; said a MEND participant in the high-dose group. &#8220;My dosage was increased to 6 [mg/kg] several days ago. There appears to be no side effects with it.&#8221;
[quote=&#8221;center&#8221;]To know that we have potentially prolonged the lives of 12 patients [in this trial] is extremely satisfying and humbling.[/quote]
Using a prognostic model, the researchers estimated that these benefits could translate in a meaningful survival extension, by 13.5 to 56.5 months depending on the severity of the disease at the time of treatment initiation. Approved treatments provide about two to nine months of additional life expectancy, the company said.
“To know that we have potentially prolonged the lives of 12 patients is extremely satisfying and humbling,” Thurn said.
The company <a href="https://alsnewstoday.com/news/fda-pharmaust-discuss-advance-monepantel-als-clinical-trials/">plans to start</a> a Phase 2/3 study to evaluate monepantel against a placebo in ALS/MND patients for 48 weeks (nearly one year). The main goal is to determine changes in disease progression and survival rates in both groups.

Vet drug monepantel slows ALS, MND disease progression in trial

New data show that blood-based measures, including levels of markers of nerve damage and chemical DNA modifications, can help predict which individuals with <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS) will have faster disease progression over time.
However, because the disease course may be altered with <a href="https://alsnewstoday.com/radicava-edaravone-for-als/">Radicava or Radicava ORS</a> — two formulations of edaravone approved in the U.S. and elsewhere for treating ALS — researchers also are looking at biomarkers that may predict the effects of these treatments in ALS patients.
&#8220;Results from this ongoing study may help to identify prognostic and disease monitoring markers of ALS and predictive &#8230; biomarkers of edaravone effect,&#8221; the scientists wrote in an abstract summarizing the findings of their work.
James Berry, MD, a professor of neurology at Harvard Medical School and a neurologist at the Massachusetts General Hospital, in Boston, presented the findings at the Muscular Dystrophy Association 2024 Clinical and Scientific Conference, being held this week in Orlando, Florida, and virtually. His talk was titled &#8220;<a href="https://www.mdaconference.org/abstract-library/interim-analysis-of-the-radicava-edaravone-findings-in-biomarkers-from-als-refine-als-study/">Interim Analysis of the Radicava/Edaravone Findings in Biomarkers from ALS (REFINE-ALS) Study</a>.&#8221;
[recommended-reading id=86236]
<h3>Scientists are seeking new biomarkers to track ALS progression</h3>
Biomarkers are objective biological measurements that can provide meaningful clinical information about a disease. To date, there are no well-validated biomarkers to track disease progression or response to treatment in people with ALS, but many potential biomarkers have been identified and have shown promise in early studies.
Radicava was <a href="https://alsnewstoday.com/news-posts/2017/05/08/fda-approves-radicava-first-new-als-therapy-in-20-years-and-cause-for-hope/">approved in the U.S.</a> as an ALS treatment in 2017, making it the first new therapy for the disease in more than two decades. The original version of the therapy is given by infusion; an oral version called Radicava ORS was <a href="https://alsnewstoday.com/news/fda-approves-radicava-ors-oral-suspension-edaravone-als/">approved in 2022</a>, and was designed to be more convenient and less burdensome for patients.
Both are given in an initial cycle of two weeks on therapy and two weeks off. In subsequent cycles, the therapy is taken daily over 10 days of the next two weeks, followed by two weeks of no treatment.
<a href="https://www.mt-pharma-america.com/">Mitsubishi Tanabe Pharma America</a>, the company that sells Radicava and Radicava ORS in the U.S., sponsored a clinical trial called <a href="https://clinicaltrials.gov/ct2/show/NCT04259255">REFINE-ALS (NCT04259255)</a> with the goal of assessing how these therapies affect potential biomarkers of ALS in the clinical setting.
The trial, which was launched in late 2019, &#8220;is designed to assess the effects of edaravone on blood biomarkers implicated in ALS in a real-world setting, as well as to look at ALS biomarkers themselves and try to give us more information about some of those,&#8221; Berry said.
The study enrolled 72 adults with ALS who started on either infused or oral Radicava formulations as part of their clinical care. Patients were followed for 24 weeks, or about six months — over six cycles of Radicava treatment.
The trial didn&#8217;t include a control arm; instead, the researchers compared findings from these participants with data from patients in a separate study called <a href="https://alsnewstoday.com/news/answer-als-project-to-better-treat-understand-disease-moves-into-new-phase/">Answer ALS</a>. For these comparisons, the researchers specifically selected patients with similar characteristics to those in REFINE-ALS, except not treated with Radicava.
[recommended-reading id=88327]
<h3>Radicava use may have slowed ALS progression in trial participants</h3>
The last patient visit in REFINE-ALS took place at the end of 2023; Berry&#8217;s presentation covered interim data collected up to about a year ago, a few months before that last patient visit.
The available data showed that, after six months on Radicava, average scores on the ALS Functional Rating Scale-Revised (ALSFRS-R), a standardized a measure of physical function, worsened by 5.3 points in REFINE-ALS. By comparison, for patients in Answer ALS, average ALSFRS-R scores worsened by 6.3 points over six months.
The difference between the two groups wasn&#8217;t statistically significant in this interim analysis, but Berry said the trend &#8220;bodes well for our final analysis.&#8221;
One of the many biomarkers being tested in REFINE-ALS is <a href="https://alsnewstoday.com/news/episwitch-test-may-help-classify-als-patients-new-trial-data/">EpiSwitch</a>, a blood test that looks for epigenetic markers — chemical changes to DNA molecules that affect which genes are active and to which extent. This test is designed to provide early prognostic information to help predict whether individuals will have slow or fast disease progression.
Based on data collected at the study&#8217;s start, or baseline, EpiSwitch predicted that about 46% of patients in REFINE-ALS and 25% in the Answer ALS group would have a fast disease progression, while the remaining individuals had slow progression.
The scientists noted that average scores on the ALSFRS-R worsened faster in fast progressors than in slow progressors in both studies, which Berry noted as a &#8220;a victory for EpiSwitch.&#8221;
However, fast progressors who received any Radicava formulation tended to have less worsening after six months than those in Answer ALS (6.7 vs. 9.1). That finding suggests that Radicava treatment may have slowed ALS progression in these patients.
[recommended-reading id=88900]
<h3>New techniques from REFINE-ALS are making trials easier on patients</h3>
Another biomarker assessed was neurofilament light chain (NfL), a structural protein in nerve fibers. When nerves are damaged, NfL is released into bodily fluids, so NfL levels in blood can be a useful way to track nerve damage.
Findings showed that patients in REFINE-ALS tended to start the study with higher levels of this biormarker than did those in Answer ALS. Also, those with higher NfL levels at the start of the REFINE-ALS trial tended to have more substantial disease progression in the following months.
Still, the team is encouraged by the data showing that, despite a &#8220;higher proportion of EpiSwitch fast predictions at baseline and a trend toward a slightly higher [NfL] at baseline in the REFINE-ALS population, we&#8217;re seeing very similar progression rates&#8221; in the two groups, Berry said.
Berry noted that other biomarkers, including measures of oxidative stress, will be included in the final analysis. Oxidative stress is a type of cell damage that occurs in ALS, and one of the main ways edaravone is thought to work is by reducing oxidative stress; thus, Berry and colleagues are particularly interested to see if they could be useful as measurements of treatment response.
&#8220;We&#8217;re encouraged by these results, and we look forward to the final analysis for what we can learn from this study,&#8221; he said.
In addition to findings from the trial itself, Berry noted that REFINE-ALS also has helped pioneer new techniques for running clinical trials.
The study launched near the start of the COVID-19 pandemic, and researchers had to quickly adapt to implement new ways to do biomarker and clinical testing without having patients come into hospitals.
Even though pandemic restrictions have eased considerably, these techniques are increasingly being used &#8220;to make trials and studies more palatable, easier for participants, and also to increase retention of participants over time,&#8221; Berry said.

MDA 2024: Blood biomarkers may help predict ALS progression rates

Denali Therapeutics&#8217; SAR443820 (DNL788) treatment candidate — now in late-stage clinical testing for <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS), per the <a href="https://www.denalitherapeutics.com/pipeline">company&#8217;s website</a> — has failed to significantly slow disease progression in adults in a Phase 2 trial.
The experimental therapy &#8220;did not meet the primary endpoint of change&#8221; in outcomes measures relative to a placebo in trial, <a href="https://www.denalitherapeutics.com/">Denali</a> reported in a Securities and Exchange Commission (SEC) <a href="https://www.sec.gov/ixviewer/ix.html?doc=/Archives/edgar/data/0001714899/000171489924000065/dnli-20240216.htm">filing</a>. That means that the HIMALAYA study, which had been testing SAR443820 versus the placebo in more than 300 ALS patients, has failed to meet its primary goal.
Detailed study results were not disclosed in the filing, but co-developer <a href="https://www.sanofi.com/en">Sanofi</a>, which is running the trial, plans to present additional safety and efficacy data at an upcoming scientific conference, Denali noted.
[recommended-reading id=36566]
<h3>Slowing ALS progression was main goal of HIMALAYA trial</h3>
SAR443820 is an oral inhibitor of RIPK1, an enzyme that plays an important role in inflammation and cell death within the central nervous system (CNS), which is comprised of the brain and spinal cord. Both inflammation and cell death are key features of many neurodegenerative diseases, including ALS and <a href="https://multiplesclerosisnewstoday.com/multiple-sclerosis-overview/">multiple sclerosis</a> (MS), for which SAR443820 also was being developed.
RIPK1 levels are found to be <a href="https://pubmed.ncbi.nlm.nih.gov/27493188/">increased in the spinal cord</a> of ALS patients.
The molecule is designed to be brain-penetrant, meaning it can cross the selective blood-brain barrier that normally prevents substances circulating in the bloodstream from entering the CNS. This barrier can pose a significant challenge to developing treatments for brain disorders.
By blocking RIPK1, SAR443820 is intended to ease neuroinflammation and cell death, thereby slowing the progression of neurodegeneration. It was awarded fast track designation from the U.S. Food and Drug Administration in 2021 for the treatment of ALS. That designation aims to speed a therapy&#8217;s clinical development.
The global <a href="https://clinicaltrials.gov/study/NCT05237284">Phase 2 HIMALAYA trial (NCT05237284)</a> enrolled 305 adults with ALS, ages 18-80, whose symptoms had emerged within the prior two years. The participants were randomly assigned to receive SAR443820 or a placebo, taken as oral tablets twice daily for 24 weeks, or about six months.
After that, all participants could enter an open-label treatment period and receive SAR443820 for about 1.5 more years (80 weeks). In an open-label study, both participants and researchers know the exact treatment patients are given.
During the trial, participants could remain on stable regimens of other ALS therapies, such as <a href="https://alsnewstoday.com/radicava-edaravone-for-als/">Radicava</a> (edaravone), <a href="https://alsnewstoday.com/amx0035/">Relyvrio</a> (sodium phenylbutyrate and taurursodiol), or riluzole (sold as <a href="https://alsnewstoday.com/rilutek-riluzole-for-als/">Rilutek</a>, <a href="https://alsnewstoday.com/tiglutik-for-als/">Tiglutik</a>, and <a href="https://alsnewstoday.com/exservan-riluzole-oral-film/">Exservan</a>). Patient <a href="https://alsnewstoday.com/news/patient-dosing-starts-phase-2-trial-oral-sar443820-als/">dosing began</a> in May 2022.
[recommended-reading id=83742]
<h3>Developers still testing SAR443820 as MS therapy</h3>
The trial&#8217;s main goal was to evaluate whether SAR443820 could slow disease progression, as assessed by changes in scores on the revised ALS Functional Rating Scale (ALSFRS-R), a commonly used measure in ALS, after 24 weeks.
While the SEC filing reported that this primary goal was not met, no information was provided regarding any secondary endpoints. Specifically, the trial was testing SAR443820 for secondary outcomes that included survival, respiratory function, muscle strength, and safety.
Sanofi acquired certain clinical development rights to SAR443820 in a <a href="https://alsnewstoday.com/news/denali-sanofi-to-develop-small-molecules-that-might-treat-als-other-diseases/">2018 collaboration agreement</a> with Denali, which also covered a number of other molecules originally developed by Denali.
One of them was a RIPK1 inhibitor called DNL747, which was being developed for ALS and <a href="https://alzheimersnewstoday.com/what-is-alzheimers-disease/">Alzheimer&#8217;s disease</a>. The companies <a href="https://alsnewstoday.com/news/denali-sanofi-pause-dnl747-studies-favor-advancing-dnl788/">paused its development in 2020</a>, and decided to shift their focus to SAR443820.
It is unclear how these findings will impact the companies&#8217; plans for SAR443820 in ALS, but the compound is still being developed as a possible treatment for MS, Denali noted in the SEC filing. In MS, the therapy also is in Phase 2 clinical testing.
&#8220;Sanofi intends to present the detailed efficacy and safety results of the ALS Phase 2 HIMALAYA study at a future scientific forum,&#8221; Denali stated in the SEC filing.

Denali therapy candidate fails to slow ALS progression in trial

Up to three years of daily treatment with the investigational therapy <a href="https://alsnewstoday.com/ipl344/">IPL344</a> was well tolerated and slowed disease progression among adults with <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS), according to top-line data from a small Phase 1/2a clinical trial.
Preliminary efficacy analyses also indicated that IPL344 might be able to increase body weight, preserve respiratory function, and prolong survival among ALS patients, as shown relative to an external placebo group.
The findings were announced by the therapy&#8217;s developer, <a href="https://immunitypharma.com/">Immunity Pharma</a>, which now plans to submit the data for publication in a scientific journal.
&#8220;These early-stage data support further development of IPL344 as a treatment for ALS, and merit further investigation in a large number of participants,&#8221; Eran Ovadia, Immunity&#8217;s CEO, said in a <a href="https://pipelinereview.com/index.php/2024011785237/Proteins-and-Peptides/Immunity-Pharma-Announces-Positive-Top-Line-Results-from-Phase-2a-Trial-with-IPL344-in-ALS-Patients.html">company press release</a>.
&#8220;We intend to progress [IPL344] to a pivotal clinical trial in ALS,&#8221; Ovadia added. That would support an application for the drug&#8217;s approval, pending positive results.
[recommended-reading id=88327]
<h3>Monthly declines in ALS progression of 48% seen with IPL344</h3>
IPL344 is a peptide designed to stimulate cellular pathways thought to be protective in ALS. It specifically activates the Akt pathway that&#8217;s involved in the survival of motor neurons — the specialized nerve cells that communicate with muscle cells to coordinate voluntary movements — which are progressively lost in ALS.
Studies indicate that <a href="https://pubmed.ncbi.nlm.nih.gov/16507768/#:~:text=Human%20skeletal%20muscle%20atrophy%2C%20as,or%20via%20another%20signaling%20pathway.">Akt signaling is diminished</a> in people with ALS. By boosting Akt activity, it&#8217;s believed that IPL344 may help to protect motor neurons and slow ALS progression.
In preclinical studies, IPL344 treatment <a href="https://www.hilarispublisher.com/proceedings/peptide-ipl344-an-akt-activator-treats-sod1-als-model-mice-to-improve-neuromuscular-function-36691.html">improved neuromuscular function</a>, prevented weight loss, and extended survival in a mouse model of ALS.
The investigational therapy has received <a href="https://immunitypharma.com/news/61-immunity-pharma-announces-that-its-novel-als-treatment-was-granted-an-orphan-drug-designation-by-both-the-fda-and-the-european-medicines-agency">orphan drug designation</a> in the U.S. and Europe — a status intended to accelerate a treatment&#8217;s clinical development by offering regulatory support and financial incentives.
The Phase 1/2a trial evaluated IPL344&#8217;s safety and preliminary efficacy among nine ALS patients, ages 18-80, at a single site in Israel. All were experiencing quickly progressing disease, defined as at least a 0.55-point monthly decline in scores on the ALS Functional Rating Scale-Revised (ALSFRS-R).
In the <a href="https://clinicaltrials.gov/ct2/show/NCT03652805">Phase 1 portion (NCT03652805)</a>, all participants received increasing daily doses of IPL344, delivered as an injection directly into the bloodstream, for 28 days, or about one month). The starting dose of 1.7 mg/kg was increased by 0.5 mg/kg every 3-4 days up to a maximum dose of 3.2 mg/kg. <a href="https://alsnewstoday.com/news-posts/2020/09/17/investigational-treatment-ipl344-safely-slows-als-progression-in-small-phase-1-2a-trial/">Interim results</a> indicated the treatment was safe and well tolerated.
Participants then continued receiving daily IPL344 for up to 36 months, or three years, in the <a href="https://clinicaltrials.gov/ct2/show/NCT03755167">Phase 2 part of the trial (NCT03755167)</a>.
Immunity now reports that IPL344-treated participants lost a mean of 0.53 points per month in the ALS Functional Rating Scale Revised (ALSFRS-R) with up to three years of treatment, reflecting a significant, 48% slowing in disease progression.
[quote=&#8221;center&#8221;]If confirmed in a subsequent larger Phase 3 study, the magnitude of reduction in ALSFRS-R progression observed in this study is greater than that achieved with currently approved drugs.[/quote]
When disease stage and other influential factors were considered in the statistical analysis, monthly declines were found to be 64% slower.
&#8220;If confirmed in a subsequent larger Phase 3 study, the magnitude of reduction in ALSFRS-R progression observed in this study is greater than that achieved with currently approved drugs,&#8221; said Ilana Cohen, PhD, Immunity Pharma&#8217;s vice president of research and development.
[recommended-reading id=88415]
<h3>Study&#8217;s participants see longer survival time compared with placebo group</h3>
Patients also experienced increases in body weight, a significant difference from a pooled group of placebo-treated patients involved in previous ALS clinical trials, in which patients continuously lost weight as the disease progressed. Those natural history data were housed in the PRO-ACT ALS patient database.
Moreover, average monthly declines in respiratory function were 44% slower on IPL344 than in the historical placebo group, though this difference was not statistically significant.
The median survival time on IPL344 was 29 months, or nearly 2.5 years, compared with 19 months, or a little longer than 1.5 years, in an external placebo group from a clinical trial of a different therapy. This comparison suggests a trend toward prolonged survival with IPL344.
For the eight patients with available data, <a href="https://immunitypharma.com/images/publications/ImmunityPharma%20NfL%20December%202023%20Poster.pdf">reductions in neurofilament light chain</a> (NfL) — a marker of nerve damage — also were observed for all but one. That patient experienced a stabilization in NfL levels. This reflects a possible neuroprotective effect of the therapy, according to Immunity.
IPL344 reportedly was well tolerated, with no major serious adverse events associated with the therapy and no treatment discontinuations due to side effects from the medication.
&#8220;We are excited that treatment with IPL344 was well tolerated in people with ALS and demonstrated encouraging signs of efficacy across multiple parameters,&#8221; Cohen said.
Long-term survival follow-up for these nine patients is ongoing. The trial initially planned to enroll 15 participants, but was suspended early due to a shortage in the investigational therapy.

Daily IPL344 for up to 3 years seen to slow ALS progression in trial

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

A memory from 12 years ago popped up on my Facebook feed. It was a video we had made for a benefit my husband’s co-workers organized for him after his <a href="https://alsnewstoday.com/als-diagnosis/">ALS diagnosis</a>.
“When I was diagnosed I thought of Danny,” Todd says at the start of the video, accompanied by photographs of a family friend who had just died of <a href="https://alsnewstoday.com/what-is-als/">ALS</a>. “He lost muscle function so fast that he could never adapt. He was always one step behind. He died a year and a half after his diagnosis.”
The video continues with clips showing Todd’s morning routine to get ready for work. I shave his head with an electric razor. Todd shaves his cheeks using both hands. I put on his belt.
Todd explains that his form of ALS is relatively slow progressing, “which is to say I lose function month by month rather than week by week.”
[recommended-reading id=82931]
Next, Todd awkwardly takes morning pills out of a 28-compartment pillbox and then swallows a handful of vitamins and supplements I had given him in a desperate attempt to stop the disease&#8217;s progression. With his weak arms, he tosses the pillbox back onto the second shelf of the cupboard.
“On most days, I don’t feel like I have a disability,&#8221; he says. &#8220;Routine tasks, like getting dressed, are difficult. But I adapt.”
He flings his arms to get a long-sleeved pullover shirt over his head. By that point in his life, he couldn&#8217;t do buttons, and he wore elastic waistband pants.
Todd sits down and puts on his cowboy boots — the easiest footwear for him to manage at the time — and talks about how the doctor had detected weakness in his left leg and suggested a sporty walking stick.
“I’m not ready for the walking stick. That, and the wheelchair, will come soon enough,&#8221; he ponders. &#8220;And when that day comes, I know our 1925 bungalow is not going to work. It is not handicap accessible, and renovations would be too expensive.”
Todd puts his computer bag over his shoulder and says goodbye to me and <a href="https://alsnewstoday.com/columns/parenting-children-rare-diseases-family-support/">the kids</a>. Our daughter is only 4 years old in the video, and I’m holding our toddler son in my arms. They were so little when our world turned upside down and our dreams were shattered.
Todd drives his truck across town and walks up to his office, ending the video with an expression of his appreciation for his co-workers and the benefit they had organized.
<h3>The stories we tell ourselves</h3>
Before Facebook reminded me of that video, I had thought back on those days as being much easier than things are now because Todd was more independent then. But watching the video brought me back to the <a href="https://alsnewstoday.com/columns/long-term-grief-wolf-like/">grief</a> and uncertainty, and the difficulty adapting to Todd’s ever-increasing disability.
The stories we tell ourselves about the past don’t always accurately reflect what we felt at the time. I sometimes forget that those days after the diagnosis were some of the hardest of my life.
I was recently going through some papers and found a notebook from 2020, when Todd had a bad cold and we were charting hour by hour the various <a href="https://alsnewstoday.com/als-treatment/">medications</a> I was giving him: guaifenesin, acetaminophen, DayQuil, Robitussin, and ipratropium bromide and albuterol administered through a nebulizer. The log starts on Feb. 10 and ends on March 1 — three weeks of intensive care as he struggled to cough and breathe and I wondered if he’d pull through. I don’t know why I saved the log, except that I felt a need to hold on to documentation of the horror we had experienced.
Todd often says that God gives us an amazing ability to forget pain. Perhaps our ability to forget is a coping mechanism to deal with trauma. Not remembering, or selective memory of suffering, can be a gift.
However, <a href="https://alsnewstoday.com/columns/grief-ongoing-loss-permission-feel-discomfort/">revisiting loss</a> can offer insight into why we’ve become the people we are. And it can even be an encouragement as we continue to face an uncertain and difficult future. I feel apprehensive as we head into the new year, not knowing what we will face in the weeks and months ahead. But we’ve survived much, so perhaps we will be able to <a href="https://alsnewstoday.com/columns/finding-strength-keep-going/">find the strength to keep going</a>.
<hr />
Note: <a href="https://alsnewstoday.com/">ALS News Today</a> is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. The opinions expressed in this column are not those of ALS News Today or its parent company, BioNews, and are intended to spark discussion about issues pertaining to ALS.

Revisiting the past offers perspective on ALS progression

People with <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS) given PrimeC in the PARADIGM Phase 2b trial — and who did not diverge in major ways from the trial&#8217;s rules — experienced a significant slowing in disease progression compared with a placebo, the treatment&#8217;s developer, <a href="https://www.neurosense-tx.com/" rel="nofollow">NeuroSense Therapeutics</a>, announced.
This finding comes from the trial’s per protocol population, an analysis covering 62 of the 68 patients randomly assigned to PrimeC or to a placebo, who adhered well to what is called a trial’s established protocol (its rules).
Recent top-line trial results, covering all 68 patients, showed a meaningful <a href="https://alsnewstoday.com/news/primec-safe-shows-trends-slowing-als-progression-paradigm-trial/">trend toward slower disease progression</a>, with a lesser <a href="https://alsnewstoday.com/symptoms-of-als/#Muscular_symptoms">decline in the muscle strength</a> needed for daily life activities, and a lesser decline in lung function and the known <a href="https://alsnewstoday.com/symptoms-of-als/#Muscular_symptoms">breathing difficulties with ALS</a>. These treatment differences relative to a placebo, however, were not statistically significant.
[recommended-reading id=88541]
<h3>PrimeC showing potential to render &#8216;significant and meaningful clinic benefit&#8217;</h3>
The new analysis in the trial&#8217;s per protocol population — focusing on the 62 patients who complied with its rules or protocol — showed a significant 37.4% reduction in functional decline, as assessed with the ALS Functional Rating Scale-Revised (ALSFRS-R).
&#8220;As we analyze the PARADIGM trial results, we continue to gain a better understanding of PrimeC&#8217;s potential to render a significant and meaningful clinical benefit to people living with ALS,” Alon Ben-Noon, NeuroSense&#8217;s CEO, said in a <a href="https://www.prnewswire.com/news-releases/neurosense-reports-new-data-statistically-significant-clinical-efficacy-in-phase-2b-als-trial-302015639.html">company press release</a>.
&#8220;Today we are eager to share these new data with the ALS community, as we believe the PP [per protocol] analysis, demonstrating a statistically significant 37.4% difference in ALSFRS-R in patients treated with PrimeC vs. placebo, is an exceptional result,&#8221; Ben-Noon added.
PrimeC is an oral fixed-dose combination of ciprofloxacin, an antibiotic used to treat bacterial infections, and celecoxib, an anti-inflammatory agent. Both have well-established safety profiles and are approved in the U.S.
The combination is thought to slow <a href="https://alsnewstoday.com/stages-of-als/">ALS progression</a> by easing inflammation and iron accumulation while improving RNA processing. These are key mechanisms known to be involved in ALS motor degeneration.
The <a href="https://clinicaltrials.gov/study/NCT05357950">PARADIGM trial (NCT05357950)</a> is testing a long-acting formulation of PrimeC, given at a total daily dose of 1,496 mg, taken as two tablets twice daily. A total of 68 adult patients were randomly assigned to either PrimeC (45 people) or a placebo (23 people) for six months, while maintaining their standard <a href="https://alsnewstoday.com/approved-treatments-for-als/">ALS treatments</a>.
The study, due to fully conclude in late 2024, set evaluations of the treatment&#8217;s safety and tolerability, and whether it can lower certain ALS biomarkers in the blood, as its primary goals. Secondary measures include changes in the patient’s ability to perform daily tasks — assessed with the ALSFRS-R — along with changes in lung function, quality of life, and survival.
<h3>Many of ALS trial&#8217;s patients continuing with PrimeC in study extensions</h3>
Top-line data shared earlier this month, covering all 68 trial participants, showed that six months of this PrimeC formulation was safe and well tolerated, with 96% of patients choosing to be treated in a one-year open-label extension. To date, all who completed these 1.5 trial years are continuing with PrimeC in an ongoing, investigator-initiated study, NeuroSense reported, without specifying the number of patients involved.
Six months of PrimeC&#8217;s use also reduced the rate of ALSFRS-R decline by 29%, and slowed the decline in lung function by 13%, compared with those receiving a placebo, top-line data showed. But these differences did not reach statistical significance.
For a better sense of the treatment&#8217;s effectiveness, a pre-specified analysis focused specifically on the per protocol group of 62 adherent patients, allowing for an assessment of treatment efficacy under optimal conditions. This is thought to provide a fair understanding of how a treatment works when used as intended.
Of these 62 patients, 43 had been randomized to treatment with PrimeC and 19 were given a placebo.
Now, six months of PrimeC use was seen to significantly slow the decline in ALSFRS-R scores by 37.4% compared with a placebo. A 17.2% reduction in lung function decline also was reported, but this difference again failed to reach statistical significance.
Results of treatment biomarker analyses are expected in the first half of 2024, NeuroSense stated. These include changes over six months in the ALS blood biomarkers TDP-43 and prostaglandin J2, as well as changes in nerve cell damage biomarkers called neurofilaments, an analysis being done in collaboration with Biogen.
&#8220;This data, in conjunction with hopefully correlative neurofilament readouts, will create a regulatory opportunity to advance PrimeC&#8217;s development in a breakthrough manner toward the market,&#8221; said Ben-Noon.
NeuroSense also announced plans for an end-of-Phase 2 meeting with the U.S. Food and Drug Administration, as well as a scientific advice meeting with the European Medicines Agency, both in the first half of 2024.
These meetings aim to discuss trial results and best approaches for PrimeC&#8217;s continued development, which is expected to include a pivotal and global <a href="https://alsnewstoday.com/news/primec-potential-als-therapy-earns-patents-in-europe-japan-israel/">Phase 3 trial of PrimeC</a> that could launch next year.

Tag: ALS progression