Masitinib linked to higher 5-year survival rate in ALS trial
Benefit appeared greatest in patients treated before severe functional loss
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- Masitinib was linked to a nearly doubled 5-year survival rate in ALS trial analyses.
- Benefit appeared greatest for patients with slower progression and treatment before severe functional loss.
- Nearly half of long-term survivors maintained satisfactory quality of life without permanent support.
Masitinib treatment was linked to a nearly doubled five-year survival rate among people with amyotrophic lateral sclerosis (ALS), with higher survival rates seen among patients with slower disease progression and those who started treatment before experiencing a complete loss of functionality.
That’s according to new analyses from the now-completed AB10015 Phase 2b/3 trial (NCT02588677), which AB Science will present at this year’s European Network to Cure ALS (ENCALS) annual meeting, taking place June 24-26 in Madrid, Spain.
The analyses also found that nearly half of patients who reached the five-year survival mark maintained a satisfactory quality of life without requiring permanent ventilation, feeding tubes, tracheostomy, or dependence on a wheelchair.
Masitinib survival data set for ENCALS presentation
“In study AB10015, the examination of long-term survivors seems to indicate a clinically relevant survival benefit for ALS patients receiving masitinib, when compared to historical standards,” Albert Ludolph, MD, PhD, chairman of the department of neurology at the University of Ulm in Germany, who will present the findings at the conference, said in a press release from AB Science.
“Notably, half of these long-term survivors preserved a high quality of life, highlighting that prolonged survival does not necessarily compromise functional independence. Additional confirmatory evidence is required to verify these encouraging results,” Ludolph added.
ALS is a progressive neurological disorder in which the nerve cells responsible for controlling muscle movement gradually become damaged and die, leading to worsening muscle weakness and loss of independence. Over time, people may lose the ability to walk, speak, swallow, and eventually breathe on their own.
Masitinib is an oral therapy being developed as an add-on treatment to slow ALS progression. The therapy works by blocking certain enzymes, called tyrosine kinases, which help regulate the activity of immune cells such as microglia and mast cells. These cells are thought to contribute to the inflammation and nerve cell damage in ALS.
In the AB10015 study, nearly 400 adults with ALS who were taking riluzole — an approved ALS treatment sold as Tiglutik and generics — were randomly assigned to receive masitinib at one of two doses (3 mg/kg or 4.5 mg/kg) or a placebo for nearly one year. Those who completed the placebo-controlled portion of the study could continue to receive masitinib in an open-label extension.
Trial showed slower ALS progression at higher dose
The trial’s main goal was to determine whether masitinib could slow disease progression, as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R), in a group of patients with normal-progressing disease at baseline, defined as a monthly decline in the ALSFRS-R score of less than 1.1 points.
In this group, patients who received the higher dose had a 27% slower disease progression relative to those on a placebo, meeting the trial’s main goal. The greatest benefit was seen in participants with mild or moderate disease at study entry who had not yet had a complete loss of physical function, meaning they did not have a score of zero on any of the 12 ALSFRS-R components.
The new findings to be presented at ENCALS build on a preprint study released earlier this year that examined long-term outcomes among 130 participants who received the 4.5 mg/kg dose in the AB10015 trial and its extension study.
Researchers reported that 42.3% of these patients, including normal and fast progressors, were alive five years after symptom onset. AB Science said this exceeded historical five-year ALS survival benchmarks, which averaged about 24% across registries. The company also cited retrospective analyses showing five-year survival rates of about 24% for riluzole-treated patients and 15%-17% for untreated patients, measured from diagnosis. Based on these comparisons, the five-year survival rate with masitinib appeared to be nearly doubled compared with historical standards.
The survival rate was even higher in certain groups of patients. Five-year survival reached 50% among participants with normal disease progression. And it was even higher — 53% — in patients with both normal-progressing disease and no complete loss of function on any ALSFRS-R item at the start of the study.
Some long-term survivors maintained quality of life
The analyses also found that among the 55 patients who survived at least five years, nearly half (49%) maintained a satisfactory quality of life without requiring permanent ventilation, feeding tubes, tracheostomy, or dependence on a wheelchair.
According to AB, these findings suggest that masitinib may not only be linked to longer survival, but also help preserve functional independence in some patients. The company noted that the greatest benefit appeared to be associated with starting treatment before severe functional impairment.
AB has launched another Phase 3 trial, called AB23005 (NCT07174492), which aims to confirm the therapy’s potential benefits and support future applications seeking regulatory approval for ALS.
In line with the benefits observed in the earlier Phase 2b/3 trial, the study will test masitinib against a placebo as an add-on to riluzole in about 412 adults with ALS who have normally progressing disease and have not completely lost physical function.
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