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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.
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<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.

PrimeC can significantly slow ALS progression, PARADIGM trial finds

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

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

<a href="https://www.neurosense-tx.com/" rel="nofollow">NeuroSense Therapeutics</a> has received key patents in Europe, Japan, and Israel covering the use of PrimeC, its investigational, fixed-dose combination therapy, in treating neurological diseases such as <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS).
These patents are valid through 2038 and join others covering Prime C&#8217;s use in the <a href="https://alsnewstoday.com/news/primec-safe-well-tolerated-us-patent-allowance-als/">U.S.</a>, Canada, and Australia. Additional patents relating to PrimeC are pending.
PrimeC is being tested in a Phase 2b clinical trial, called <a href="https://classic.clinicaltrials.gov/ct2/show/NCT05357950">PARADIGM (NCT05357950)</a>, which <a href="https://alsnewstoday.com/news/neurosense-paradigm-trial-primec-als-completes-enrollment-patients/">enrolled 69 adults with ALS</a> at sites in Israel, Italy, and Canada. The company expects to present top-line trial data in the coming months.
Should results be promising, a pivotal and global Phase 3 clinical trial in ALS patients is planned for 2024.
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<h3>PrimeC showed safety and potential efficacy in earlier ALS clinical trial</h3>
&#8220;We are pleased to receive this most recent patent grant in Europe, Japan, and Israel which adds to our growing [intellectual property] estate as we expect the clinical read-out from our PARADIGM Phase 2b study towards year&#8217;s end,” Alon Ben-Noon, NeuroSense’s CEO and co-founder, said in a <a href="https://www.prnewswire.com/news-releases/neurosense-granted-patents-in-europe-japan-and-israel-for-its-als-drug-primec-301931701.html">press release</a>.
“ALS remains a pressing unmet need, and our unwavering commitment to advancing our program, supported by robust intellectual property, underscores our dedication to delivering an effective therapy for individuals battling ALS,&#8221; Ben-Noon added.
The company also was given Small and Medium-Sized Enterprise (SME) status by the European Medicines Agency (EMA) and opened an office in Germany, NeuroSense reported in a <a href="https://www.prnewswire.com/news-releases/european-medicines-agency-grants-neurosense-sme-status-301933411.html">separate press release</a>. The designation offers multiple benefits, including regulatory guidance throughout clinical development, financial benefits, and facility inspections, as well as fee exemption in the first years should the therapy be approved.
<a href="https://www.neurosense-tx.com/primec/" rel="nofollow">PrimeC</a> is an oral, fixed-dose combination of ciprofloxacin, an antibiotic, and celecoxib, an anti-inflammatory medication. The two compounds have well-established safety profiles and are approved in the U.S.
Used together, these medicines may have the potential to prevent disease progression by targeting key mechanisms that contribute to the degeneration of motor neurons, the nerve cells affected in ALS. Specifically, PrimeC is designed to reduce inflammation and iron accumulation, and to improve RNA processing.
In a previous <a href="https://classic.clinicaltrials.gov/ct2/show/NCT04165850">Phase 2a clinical trial (NCT04165850)</a> in Israel, an initial formulation of PrimeC taken three times daily was found to be <a href="https://alsnewstoday.com/news/primec-safe-lowers-als-disease-biomarkers-phase-2-clinical-study/">safe and well tolerated in ALS patients</a>. It also was seen to slow declines in the ability to perform daily activities and in lung function compared with an historical group of patients.
<h3>Phase 2b clinical trial of PrimeC to be followed by open-label extension</h3>
A new, extended-release formulation of PrimeC then was developed to be longer acting, requiring twice daily dosing. That formulation is being tested in the PARADIGM trial, with Prime C or a placebo given patients twice a day for six months.
Participants, ages 18 to 75 and whose symptoms of muscle weakness started less than 2.5 years before enrollment, also are continuing on their standard <a href="https://alsnewstoday.com/als-treatment/">ALS medications</a>.
The trial’s main goals are to evaluate PrimeC’s safety and tolerability, as well as changes in ALS biomarkers. Secondary goals will investigate the treatment&#8217;s efficacy on motor abilities, lung health, quality of life, and survival.
After completing the trial, patients can join an open-label extension phase, where all will be treated for up to one year.
PrimeC was designated an <a href="https://alsnewstoday.com/news/als-combination-therapy-primec-receives-fdas-orphan-drug-designation-enters-clinical-trials/">orphan drug in the U.S.</a> and the <a href="https://alsnewstoday.com/news/primec-orphan-drug-designation-europe-treatment-als/">European Union</a>. This status is given to therapies that aim to treat rare diseases and provides several benefits, including exemption from regulatory fees, assistance with clinical trial protocols, and several years of market exclusivity upon approval.

Tag: NeuroSense Therapeutics

PrimeC can significantly slow ALS progression, PARADIGM trial finds

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

PrimeC, potential ALS therapy, earns patents in Europe, Japan, Israel