Early PrimeC initiation slows lung function decline, trial data show
Disease progression seen slower in patients who started treatment early
People with amyotrophic lateral sclerosis (ALS) who received one year of treatment with PrimeC, an experimental oral tablet from NeuroSense Therapeutics, lived significantly longer without disease complications and had a slower lung function decline than those who started treatment six months later.
That’s according to the latest results from PARADIGM (NCT05357950), a Phase 2b clinical study in 68 ALS adults testing PrimeC against a placebo, both taken twice daily for six months. Some 96% of participants chose to enter an open-label extension in which all are receiving PrimeC for up to 12 months.
The findings come after results showed that ALS patients on PrimeC for one year saw extended survival and significantly slower disease progression than those who started on a placebo and received PrimeC with a six-month delay.
The results support PrimeC as a disease-modifying treatment that’s best started earlier in the disease. NeuroSense plans to work with the U.S. Food and Drug Administration (FDA) and other regulatory agencies to discuss the next steps in PrimeC’s clinical development.
“We believe that these results are unprecedented in a 12-month ALS placebo-controlled clinical study,” Alon Ben-Noon, NeuroSense’s CEO, said in a company press release. “We are eager to present them to the FDA and other regulatory agencies to determine the path forward and to share the outcomes with potential partners currently conducting due diligence.”
Machine learning to help develop protocol for future study
The company is collaborating with PhaseV to develop a machine learning model that provides insights into how to better design the clinical protocol for a planned Phase 3 study based on how well patients responded to PrimeC during Phase 2b testing.
“I am eagerly looking forward to seeing the program enter Phase 3 to advance the clinical development of this product,” said Jeremy M. Shefner, MD, PhD, a professor of neurology at the Barrow Neurological Institute in Phoenix and an adviser to NeuroSense.
PrimeC is a fixed-dose, extended-release formulation of two FDA-approved medications: the antibiotic ciprofloxacin and celecoxib, an anti-inflammatory drug. The two molecules are expected to work in synergy to block key ALS mechanisms, slowing disease progression.
Top-line results from the PARADIGM study showed that patients assigned to receive PrimeC for six months tended to experience slower disease progression, as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R), and lung function decline compared with those on a placebo.
These differences failed to reach statistical significance, but data from the extension part did show a significant, 36% slowing of disease progression after one year when patients initially on a placebo had been on active treatment for six months.
Patients who received PrimeC for the whole year also had a 43% lower risk of death than those who started with a six-month delay.
The newly announced one-year results showed that complication-free survival, or the time patients lived without complications such as respiratory failure, hospitalization due to ALS, or advances in ALS disease stages, was also extended by 57% among patients who were on PrimeC from the start.
Likewise, slow vital capacity, a measure of lung function, declined 20% slower among patients who received one year of treatment compared with those who started it six months later.
Benefits clearer in those who adhered to protocol
Over PARADIGM and its extension, the benefits of PrimeC were generally more pronounced in a group of 62 patients who adhered well to the clinical protocol — called the trial’s per-protocol population.
In this group, PrimeC significantly slowed disease progression by 37.4% compared with a placebo after six months, and one-year data showed a 63% improvement in survival rates and a 40% reduction in disease progression rates over delayed treatment.
The new data also showed that complication-free survival was better in this group, with patients given one year of treatment living 73% longer without complications compared with those who started six months later. Slowed vital capacity, on the other hand, had a 19% difference between groups.
After 12 months, the proportion of patients who experienced a drop of 4 or fewer points on the ALSFRS-R was about 4.5 times higher among those who received PrimeC for one year compared with those who started treatment later.
“The latest results from the PARADIGM study are incredibly encouraging,” Shefner said. “The substantial improvement in complication-free survival and the consistent slowing of disease progression highlight PrimeC’s promise as an effective treatment.”
So far, all patients who completed the full 18 months of PARADIGM have asked to continue on PrimeC, which is being provided in an investigator-initiated study that doesn’t have a set end date, according to the company.
“We look forward to continued communications on developments, as appropriate, including biomarker readouts for target engagement, which we expect will shed additional light on PrimeC’s potential,” said Ben-Noon.
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