5-year survival seen for over 40% of ALS patients on masitinib in trial
For half, no need for tube feeding, wheelchair or ventilation, analysis finds
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- Masitinib treatment for ALS led to 42% of patients in a clinical trial surviving five years, nearly double historical rates, an analysis found.
- About half of these long-term survivors maintained good quality of life.
- Early masitinib use improved outcomes; a new Phase 3 trial is planned.
Nearly half of the people with amyotrophic lateral sclerosis (ALS) treated with masitinib in a clinical trial survived for at least five years from disease onset — a marked improvement over historical data showing fewer than 1 in 4 ALS patients typically live this long — indicating what the therapy’s developer called “substantial survival benefits.”
Those are the findings of new analyses of data from the now-completed AB10015 Phase 2b/3 trial (NCT02588677), which were shared by AB Science, the company developing masitinib. The results also demonstrated that 49% of patients who survived at least five years maintained a satisfactory quality of life, without needing tube feeding, ventilatory support, or being dependent on a wheelchair.
The study, “Evaluation of Long-Term Amyotrophic Lateral Sclerosis Survivors Treated with Masitinib in Study AB10015,” was published as a preprint in MedRxiv. Being a preprint means the study has not yet been edited and undergone peer review, the process where outside scientists assess a manuscript for technical issues.
“This analysis of long-term survivors in study AB10015 appears to reveal a substantial and clinically meaningful survival advantage for ALS patients treated with masitinib as compared to historical benchmarks,” Albert Ludolph, MD, lead author of the study at the University of Ulm in Germany, said in a press release from AB Science announcing the analysis’ findings.
“Most importantly, half of these long-term survivors maintained a good quality of life, underscoring that extended survival need not come at the expense of their functional independence,” Ludolph said.
Masitinib is an oral therapy designed to reduce inflammation in the nervous system, which is thought to contribute to the progressive loss of motor neurons, the nerve cells that control movement, in ALS.
New analysis used data from clinical trial testing masitinib
The AB10015 trial tested two doses of the experimental therapy — 3 or 4.5 mg/kg — against a placebo in nearly 400 ALS patients who were also taking the approved therapy riluzole (sold as Tiglutik and generics). After the placebo-controlled part of the trial ended, participants had the option to continue receiving the medication as part of an open-label extension.
The study’s main goal was to determine if masitinib could slow disease progression, as measured using the ALS Functional Rating Scale-Revised (ALSFRS-R). Results showed the higher dose slowed disease progression by 27%, with greater effects seen in patients who had mild or moderate ALS at the study’s start.
AB Science is now gearing up for a larger Phase 3 study, AB23005 (NCT07174492), which hopes to confirm these findings and serve as a basis for applications seeking the approval of masitinib for treating ALS.
In the new manuscript, researchers tracked long-term survival outcomes from 130 people who received the 4.5 mg/kg dose of masitinib in the Phase 2b/3 trial and its open-label extension.
Although there is no standard definition of ‘long survival’ in ALS, the literature indicates that surviving at least five] years from the onset of symptoms surpasses expectations regarding median survival.
Those results showed that 42% of the patients were still alive five years after disease onset. To put that in perspective, the researchers said historical data indicate that typically about 24% of ALS patients will survive this long — meaning that the odds of such long-term survival appear to be almost doubled with masitinib.
“Although there is no standard definition of ‘long survival’ in ALS, the literature indicates that surviving at least [five] years from the onset of symptoms surpasses expectations regarding median survival,” the scientists wrote.
Researchers urge treatment start ‘as early as possible’
The ALSFRS-R scale consists of a dozen items assessing how much difficulty an individual has accomplishing various tasks, with a score of zero indicating that the person cannot do the task at all.
The researchers noted that the five-year survival rate was markedly higher, at 53%, in patients who started the study with a score of at least one on each of the 12 items.
According to AB, this finding is consistent with previous analyses indicating that starting masitinib earlier, before patients have totally lost functional abilities, can lead to better long-term outcomes. These data are also consistent with masitinib’s mechanism of action, which is designed to help preserve motor neurons.
“In essence, masitinib is designed to slow disease progression rather than restore lost functions; therefore, administering masitinib as early as possible, while there is still good functionality, aligns better with its intended mechanism,” the researchers wrote.
The researchers also noted that, among the 55 patients who survived for at least five years after symptoms emerged, about half (49%) had no need for permanent mechanical assistance, such as a ventilator, feeding tube, and/or wheelchair.
Further, among patients who survived at least five years, median overall survival time was 121 months, or more than 10 years, after disease onset. Statistical models based on historical data, by contrast, suggest these patients would have lived a median of 42 months, or about 3.5 years, without masitinib — representing a survival gain of 79 months, or about 6.5 years, with the treatment.
An important caveat of these analyses is that the researchers were comparing against historical data, meaning other factors besides masitinib treatment might also be influencing the results. As such, the upcoming Phase 3 trial will be necessary to further evaluate the impact of masitinib on ALS progression.
“Further confirmatory evidence will be crucial for translating these promising findings into clinical practice,” Ludolph said.
AB Science stated in the release that the analysis “[demonstrates] substantial survival benefits and preserved quality of life with masitinib in ALS patients.”
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