PrimeC normalizes iron biomarkers in Phase 2b ALS trial
New data follow results showing treatment slows disease progression
One year of treatment with the experimental oral therapy PrimeC led to improved iron accumulation in people with amyotrophic lateral sclerosis (ALS), according to new clinical trial data announced by PrimeC’s developer, Neurosense Therapeutics.
Previous results showed that people who received PrimeC for one year experienced significantly slower disease progression and better survival outcomes than patients who transitioned from a placebo after the first six months.
“This new analysis highlights PrimeC’s ability to regulate the iron panel in people living with ALS, underscoring the drug’s target engagement,” Merit Cudkowicz, MD, chair of neurology and director of the Sean M. Healey and AMG Center for ALS at Massachusetts General Hospital, said in a company press release.
ALS is driven by the death and degeneration of motor neurons, the specialized nerve cells that control voluntary movements. While the causes of ALS aren’t fully understood, at the molecular level, one of the disease’s features is an overload of iron in nerve cells. Iron is an essential nutrient that’s key for many biological functions in the body, but excess iron drives cellular damage, which is thought to play a role in ALS progression.
Combination of medicines
PrimeC is a fixed-dose combination of two medicines that are already approved individually in the U.S.: ciprofloxacin, an antibiotic, and celecoxib, an anti-inflammatory medicine. Working in tandem, these two components are thought to target key ALS disease processes, including iron accumulation and inflammation in the brain.
PrimeC is being tested in a Phase 2b clinical trial called PARADIGM (NCT05357950). The study enrolled 68 participants, who were randomly assigned to take the experimental therapy or a placebo for six months. After the placebo-controlled part of the trial, most participants entered an open-label extension in which they are all being given PrimeC for about a year.
Neurosense recently announced one-year data from PARADIGM demonstrating that patients given PrimeC for a full year had 36% slower disease progression and 43% better survival than those who’d been on placebo for the first six months. Previously announced data also indicated the therapy helped slow the decline in lung function after a year of treatment.
“The 12-month results from the PARADIGM Phase IIb study are encouraging, showing slowing of disease progression and improved survival outcomes,” Cudkowicz said.
The new data concern one-year findings for two biomarkers of iron metabolism: ferritin, a protein that works to store iron inside of cells, and transferrin, a protein that helps move iron out of cells. In ALS, iron accumulation is marked by an increase in ferritin levels and a corresponding decrease in transferrin levels.
Findings showed that, compared with those initially given placebo, patients on PrimeC for a full year saw decreased ferritin levels and correspondingly increased transferrin levels — implying a relative normalization in iron levels within cells. The average difference in iron levels was 4.536 micromoles per liter.
Cudkowicz said the new data “strongly support the proceeding to phase 3 testing of PrimeC in ALS.” A Phase 3 trial of PrimeC in ALS is currently being designed, and the company is gathering more data to discuss the best path forward with the U.S. Food and Drug Administration (FDA).
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