A SUPER-powered WP Engine Atlas Test Site

Joe&#039;s Atlas Experimentation Site

NeuroSense Therapeutics’ PrimeC was found to be safe and well tolerated in a Phase 2b trial, and use of the oral therapy for six months led to &#8220;meaningful slowing of disease progression&#8221; in people with <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS), the company said in a <a href="https://www.prnewswire.com/news-releases/neurosenses-phase-2b-als-trial-achieves-primary-safety-and-tolerability--secondary-clinical-efficacy-endpoints-302005837.html">press release</a> announcing top-line results.
The new data comes from <a href="https://clinicaltrials.gov/study/NCT05357950">PARADIGM (NCT05357950)</a>, a <a href="https://alsnewstoday.com/news/neurosense-paradigm-trial-primec-als-completes-enrollment-patients/">fully enrolled</a> clinical trial that&#8217;s testing PrimeC against a placebo in 69 adults with a <a href="https://alsnewstoday.com/als-diagnosis/">diagnosis of ALS</a>.
The positive findings will now support the launch of a pivotal and global Phase 3 trial that&#8217;s <a href="https://alsnewstoday.com/news/primec-potential-als-therapy-earns-patents-in-europe-japan-israel/">planned for 2024</a>. The U.S. Food and Drug Administration (FDA) already has <a href="https://alsnewstoday.com/news/fda-oks-neurosenses-cmc-primec-ahead-phase-3-trial/">agreed to the manufacturing practices</a> and product specifications set in place ahead of the trial.
“The release of this portion of the top-line results of the PARADIGM trial marks an exciting milestone for NeuroSense as we take another step toward helping people suffering from this dire disease,” said Alon Ben-Noon, <a href="https://www.neurosense-tx.com">NeuroSense</a>’s CEO.
According to the release, PrimeC &#8220;achieved primary safety and tolerability endpoints [goals] with a safety and tolerability profile comparable to [a] placebo.&#8221;
[recommended-reading id=87331]
<h3>Use of PrimeC in PARADIGM leads to 29% slower disease progression</h3>
NeuroSense also is planning to report the results of biomarker analyses from the PARADIGM trial in the first half of 2024.
These include changes in ALS blood biomarkers TDP-43 and prostaglandin J2 after six months — one of the trial&#8217;s main goal. The company also expects to share its findings on changes in neurofilament blood levels, a biomarker of nerve cell damage. That analysis is being done in collaboration with <a href="https://www.biogen.com/">Biogen</a>.
“We look forward to meeting with the FDA to determine the best path forward and to advancing discussions with strategic partners who share our vision for PrimeC to benefit people living with ALS,” Ben-Noon said.
PrimeC contains a fixed-dose combination of two FDA-approved medications: ciprofloxacin, an antibiotic used to treat bacterial infection, and celecoxib, a medicine for relieving pain and inflammation. It is expected to slow <a href="https://alsnewstoday.com/stages-of-als/">disease progression</a> by blocking key mechanisms behind ALS.
PARADIGM, slated for completion in fall of 2024, is testing a long-acting formulation of PrimeC, which releases the medications in the body over time. In the trial, PrimeC was given at a total daily dose of 1,496 mg, taken as two tablets twice daily.
A total of 69 adults with ALS — taking part in the study at sites in Canada, Italy, and Israel — were randomly assigned to receive the medication or a placebo for six months. Data was gathered from 68 patients, due to one misdiagnosis.
The trial&#8217;s main goals are to determine if PrimeC is safe and well tolerated in ALS patients, and whether it reduces the amount of ALS biomarkers in circulation, indicating a potential effect on disease processes.
Secondary measures include changes in the ability to perform daily tasks, as assessed with the ALS Functional Rating Scale-Revised (ALSFRS-R), as well as changes in lung function, quality of life, and survival.
Over the trial&#8217;s six months, safety and tolerability profile of PrimeC was comparable to that of the placebo.
[quote=&#8221;center&#8221;]In addition to the safety and tolerability profile observed, we believe the 29% difference observed in ALSFRS-R in favor of PrimeC as well as the 13% decline in [lung function] compared to the placebo arm, illustrate PrimeC&#8217;s potential to render a meaningful clinical benefit to people living with ALS.[/quote]
Also, patients treated with PrimeC experienced a 29% slower disease progression on the ALSFRS-R scale, as well as a 13% slower decline in lung function, compared with those given a placebo. These differences failed to reach statistical significance, but the company noted that this trial was not powered to detect such significant difference.
&#8220;In addition to the safety and tolerability profile observed, we believe the 29% difference observed in ALSFRS-R in favor of PrimeC as well as the 13% decline in [lung function] compared to the placebo arm, illustrate PrimeC&#8217;s potential to render a meaningful clinical benefit to people living with ALS,&#8221; said Ferenc Tracik, MD, NeuroSense’s chief medical officer.
After completing the six months of dosing, most participants (96%) chose to enter an open-label extension, in which all are being treated with PrimeC for up to one year. So far, all who completed 1.5 years of treatment have opted to continue taking PrimeC by joining an ongoing investigator-initiated trial.
“I am excited by the top-line clinical data from PARADIGM, as this is an important milestone for the patients I care for and for the entire ALS community,” said Merit Cudkowicz, MD, chair of neurology at the Massachusetts General Hospital and director of the Healey &amp; AMG Center for ALS in Boston.
“The positive results support moving forward to a Phase 3 pivotal trial. The biomarker data will also be very informative, and I look forward to seeing those results in early 2024,” added Cudkowicz, who is also a member of NeuroSense’s scientific advisory board.

PrimeC safe, shows trends toward slowing ALS progression: Trial data

People with <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS) are not at a higher risk of complications due to a spinal tap than are healthy individuals or those with other neuromuscular disorders, according to a small U.S. study.
Findings show that ALS patients have a relatively lower risk for such adverse events, with the most common side effect of a spinal tap, also known as a <a href="https://alsnewstoday.com/spinal-tap-lumbar-puncture/">lumbar puncture</a>, being headaches.
&#8220;Our findings demonstrate that [lumbar puncture] is a safe procedure for participants with ALS, with a similar or lower rate of [adverse events] than in participants without ALS,&#8221; the researchers wrote.
The study, “<a href="https://onlinelibrary.wiley.com/doi/10.1002/mus.27956">Lumbar punctures are safe in patients with ALS and have a risk profile similar to that in the non-ALS population</a>,” was published in the journal <a href="https://onlinelibrary.wiley.com/journal/10974598">Muscle &amp; Nerve</a>.
[recommended-reading id=86923]
<h3>Spinal taps can be of help in diagnosing and monitoring ALS</h3>
A spinal tap often is given to people with ALS to collect a sample of the cerebrospinal fluid (CSF) — the transparent liquid surrounding the brain and spinal cord. The analysis looks for biomarkers that help in the diagnosis and monitoring of patients, as well as in assessing responses to treatments.
<a href="https://alsnewstoday.com/ionis-sod1-rx-biib067/">Qalsody</a> (tofersen), a recently approved ALS treatment, also is given via an injection into the spinal canal, which is in many ways similar to a spinal tap.
The procedure has been deemed safe in people with neurodegenerative diseases like <a href="https://alzheimersnewstoday.com/what-is-alzheimers-disease/">Alzheimer’s</a>, but its safety in ALS remains unknown.
A team led by researchers at Washington University in St. Louis School of Medicine, partly because of <a href="https://alsnewstoday.com/news/fda-approves-tofersen-now-qalsody-treatment-adults-sod1-als/">Qalsody&#8217;s approval in the U.S.</a>, set out to assess whether ALS patients are at an increased risk of complications after a spinal tap. They conducted a retrospective analysis of people who had undergone a spinal tap, for research purposes, at the university&#8217;s ALS Center between 2015 and 2021.
In total, 233 people underwent a spinal tap during those years: 63 healthy adults, 154 ALS patients, and 16 adults with a neuromuscular disease other than ALS. The groups were fairly similar in their demographics, although the patient groups generally had higher rates of high blood pressure, psychiatric conditions, and headaches.
About one week after the procedure, participants were evaluated for adverse events by phone, and some events were reported by the person who did the procedure. Serious side effects were those requiring medical intervention.
Adverse events were reported to affect 49 (21%) of these 233 people — 18 (28.6%) in the healthy group, 28 (18.2%) in the ALS group, and three (18.8%) in the group with another neuromuscular disease.
The most common side effect was headache, followed by back pain and vasovagal response — fainting due to a problem in the part of the nervous system that regulates heart rate and blood pressure.
Three cases of headaches — one in each group — were deemed serious, and required a subsequent epidural blood patch. In this procedure, blood is injected into the site of the spinal tap to form a blood clot (patch), essentially &#8220;plugging&#8221; the puncture hole.
<h3>Serious risk of spinal tap complications not seen for ALS patients</h3>
Study findings illustrated that ALS patients were not more likely to experience adverse events after a spinal tap than other patient groups or healthy adults. In fact, the risk of a post-puncture headache was significantly lower, by about 64%, among ALS patients relative to healthy individuals, and among these patients compared with both of the other groups.
No link was found between adverse events and age, as well as with other co-existing conditions or comorbidities, like high blood pressure. However, women were significantly more likely than men to experience headaches after a spinal tap.
&#8220;Our study shows no increased risk of post-LP [lumbar puncture] complications in people living with ALS relative to controls. Instead, our data suggest that people living with ALS are at a relatively lower risk of developing post-LP complications,&#8221; the researchers concluded.
&#8220;Awareness of these findings could allow for better design of existing ALS research involving LPs and aid in discussions of LP safety with participants — with the goal of alleviating their fears … and improving patient participation. This is of particular importance as we move into an age of ALS therapeutics delivered via intrathecal [spinal canal] injection,&#8221; they added.

Spinal taps can be given safely to ALS patients, small study reports

VRG50635, an experimental oral therapy being developed by <a href="https://www.vergegenomics.com">Verge Genomics</a> for <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS), was found to be safe and well-tolerated in healthy volunteers, new Phase 1 trial data show.
Top-line data from the <a href="https://www.isrctn.com/ISRCTN14792372">trial (ISRCTN14792372)</a> also showed a promising tolerability and pharmacological profile supporting once-daily dosing.
The company is now planning to advance the treatment into a proof-of-concept study in people with <a href="https://alsnewstoday.com/sporadic-als/">sporadic</a> and <a href="https://alsnewstoday.com/forms-of-als-familial-als/">familial ALS</a> that’s expected to start in the final months of 2023.
“We are extremely encouraged by these initial results which highlight the favorable safety and tolerability profile of VRG50635,” Diego Cadavid, MD, chief medical officer of Verge, said in a <a href="https://www.businesswire.com/news/home/20230615018038/en/Verge-Genomics-Announces-Positive-Safety-and-Tolerability-Data-from-the-Phase-1-Clinical-Trial-of-VRG50635-a-Potential-Best-in-Class-Therapeutic-for-All-Forms-of-ALS">company press release</a>.
[recommended-reading id=21684]
<h3>VRG50635 works to block PIKfyve, identified by AI as therapeutic target</h3>
VRG50635 is a small molecule designed to block the PIKfyve protein, a potential therapeutic target in ALS. PIKfyve was identified by the company’s artificial intelligence (AI) platform after sorting a large amount of biological data stemming from brain and spinal cord samples of ALS patients.
The protein is thought to play a role in the endolysosomal pathway, a kind of recycling system inside cells that helps break down faulty or unneeded molecules to keep the cells clean and functioning properly.
In ALS patients, this recycling system is usually not working as needed, leading to the buildup of toxic protein clumps — a hallmark of the disease known to contribute to the death of motor neurons and the progression of <a href="https://alsnewstoday.com/symptoms-of-als/">symptoms</a>. Motor neurons are the nerve cells that control muscle movement and are progressively lost in ALS.
VRG50635 <a href="https://alsnewstoday.com/news/verge-starts-first-human-trial-pikfyve-inhibitor-als/">advanced from discovery</a> to a first-in-human trial in four years. In the lab, it extended survival of nerve cells from ALS patients and models of motor neuron degeneration.
“The lack of predictive animal models is one of the greatest challenges to developing effective ALS therapies today,” said Alice Zhang, CEO and co-founder of Verge. “This is why we’re excited to advance VRG50635, a drug derived directly from human data, into trials in people with ALS.”
The Phase 1 trial tested VRG50635 versus a placebo in 80 healthy adult volunteers. The therapy was given at different doses once or multiple times over one week, starting with a low dose of 60 mg and gradually increasing it up to 1,800 mg in subsequent groups.
There were no serious side effects, and VRG50635 was considered safe. The therapy was also deemed well-tolerated at the highest planned dose.
Data also showed the maximum concentration of VRG50635 in the body and the total exposure to the drug increased in proportion to the dose. Its active metabolite had a half-life (the time taken for its concentration to reduce by half) of about 37 hours, suggesting that VRG50635 may be taken by mouth once daily.
[recommended-reading id=84924]
<h3>Data to be presented at upcoming European conference in Barcelona</h3>
More detailed data will be presented at the upcoming European Network to Cure ALS (ENCALS) 2023 meeting, which will be held July 12-14 in Barcelona, Spain.
“We look forward to sharing additional information at the ENCALS meeting in Barcelona next month and anticipate progressing to a proof-of-concept study in patients with sporadic and familial ALS later this year,” Cadavid said.
According to Zhang, the study is “designed to overcome historical challenges in ALS clinical trials by using state of the art technology, such as digital at-home devices and blood-based biomarkers, that can capture richer, higher-fidelity patient data and have the potential to detect efficacy with greater sensitivity.”

Tag: safety

PrimeC safe, shows trends toward slowing ALS progression: Trial data

Spinal taps can be given safely to ALS patients, small study reports

Potential ALS therapy, VRG50635, found to be safe in healthy adults