PrimeC safe, shows trends toward slowing ALS progression: Trial data
Positive findings from PARADIGM support launch of pivotal trial in 2024
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 “meaningful slowing of disease progression” in people with amyotrophic lateral sclerosis (ALS), the company said in a press release announcing top-line results.
The new data comes from PARADIGM (NCT05357950), a fully enrolled clinical trial that’s testing PrimeC against a placebo in 69 adults with a diagnosis of ALS.
The positive findings will now support the launch of a pivotal and global Phase 3 trial that’s planned for 2024. The U.S. Food and Drug Administration (FDA) already has agreed to the manufacturing practices 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, NeuroSense’s CEO.
According to the release, PrimeC “achieved primary safety and tolerability endpoints [goals] with a safety and tolerability profile comparable to [a] placebo.”
Use of PrimeC in PARADIGM leads to 29% slower disease progression
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’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 Biogen.
“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 disease progression 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’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’s six months, safety and tolerability profile of PrimeC was comparable to that of the placebo.
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’s potential to render a meaningful clinical benefit to people living with ALS.
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.
“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’s potential to render a meaningful clinical benefit to people living with ALS,” 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 & 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.
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