IFB-088 slows disease progression in bulbar-onset ALS trial
Treatment safe, well tolerated, data show
Oral therapy IFB-088 (icerguastat) was safe and significantly slowed disease progression in certain people with amyotrophic lateral sclerosis (ALS), according to new data from a Phase 2 clinical trial.
“We are very encouraged by the results we observed with IFB-088,” Pierre Miniou, CEO of IFB-088’s developer Inflectis Bioscience, said in a company press release. “These compelling findings position IFB-088 for forthcoming pivotal studies and pave the way for new treatment possibilities for ALS,” he said.
The Phase 2 P288ALS TRIAL (NCT05508074) enrolled 51 people with bulbar-onset ALS, a form of the disease that initially affects muscles around the mouth and throat, leading to difficulty speaking and swallowing.
Participants were randomly assigned to take IFB-088 tablets, at a dose of 25 mg twice daily, or a placebo. All participants also received treatment with the approved ALS therapy riluzole, which is sold as Rilutek, Tiglutik, and Exservan. Data for at least six months was available for 41 patients.
The study’s main goal was to evaluate the safety of IFB-088 in bulbar-onset ALS patients. Results overall were positive, with the therapy being deemed safe and well tolerated. According to Inflectis, there were “non-meaningful observations,” but the company didn’t provide specifics on safety outcomes.
Disease progression trends slower
“New treatments are urgently needed to make ALS a livable disease, so we are thrilled to see IFB-088 hit its primary endpoint of safety and tolerability,” said Kuldip Dave, PhD, senior vice president for research at the ALS Association. “This is a critical first step in taking the program forward into larger trials that can determine efficacy.”
While the trial was not designed to assess efficacy and the number of participants was too small to draw reliable conclusions on efficacy measures, the early data look promising, Inflectis said.
In the population of 51 randomized patients, there was a trend toward a slower disease progression on the ALS Functional Rating Scale Revised (ALSFRS-R), a standardized measure of patients’ ability to perform a number of day-to-day activities, in people receiving IFB-088 compared with the placebo group.
This difference became significant in the 40 patients who closely adhered to their treatment schedule, called the per protocol population. In this group, patients given IFB-088 lost on average 0.95 points per month on the ALSFRS-R, a statistically significant and clinically meaningful difference from the 1.42 points that those on a placebo lost per month.
Measures of lung function and ALS staging systems in the per protocol population also tended to indicate slower progression with IFB-088 than a placebo, according to Inflectis.
“These findings confirm the hypotheses raised from preclinical studies and strongly support the premise of moving IFB-088 to pivotal study,” said Anne Visbecq, MD, chief medical officer of Inflectis.
IFB-088 is designed to treat ALS through a combination of several simultaneous molecular mechanisms. The therapy activates the integrated stress response, which is a biochemical pathway that cells use to deal with stressors. IFB-088 is also designed to limit a type of cell damage called oxidative stress and to reduce excitotoxicity, a phenomenon in which nerve cells fire too much and become damaged.
Biomarker data from the Phase 2 study indicate that IFB-088 was activating the integrated stress response and reducing oxidative stress as designed, according to Inflectis. The data also suggest the therapy helped reduce inflammation and nerve damage, as well as abnormalities in the TDP43 protein, which are a molecular hallmark of ALS thought to contribute to nerve damage.
“The positive results, supported by both clinical outcomes and biomarker validation, while confirming our previous work, strengthen the therapeutic potential of targeting the integrated stress response (ISR) and oxidative stress pathways in bulbar onset ALS,” said Giuseppe Lauria, MD, principal investigator of the study and professor of neurology at the University of Milan. “These findings provide a strong foundation for further clinical development and bring us one step closer to delivering an innovative and effective treatment to patients.”
Inflectis is “seeking global partners to complete the development and registration of IFB-088 in ALS and leverage the company’s assets in a broader pipeline of neurological indications with unmet medical needs,” Miniou said.
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