France’s AB Science (OTCPK:ABSCF) seems to have notched up an unexpected positive interim readout in a phase III study with its c-KIT inhibitor, masitinib, in the difficult indication of amyotrophic lateral sclerosis (ALS). The result could represent the first progress in the ALS field in more than two decades.
AB Science has not disclosed the details of the results to avoid confounding the study, which will continue to its planned completion to obtain more data. If successful, it could be the second indication in which AB will seek regulatory approval in quick succession.
The study has recruited 382 patients and is testing two doses of masitinib (3 and 4.5mg/kg/day) vs placebo on top of riluzole, the only drug currently approved for ALS. The interim analysis was performed when 191 patients had completed 48 weeks of treatment and, as is normal, had to meet a high statistical hurdle for declaring success. In this case, the study had to detect a three point difference between active and control arms on the primary endpoint of revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALFRS-R) in the ITT population, with a p-value of below 0.0311.
Prior studies suggest ALS patients typically deteriorate by one point per month, so patients on the control arm were expected to change by around 12 points over a 48 week treatment period. The study was therefore to detect a 25% difference in deterioration, a difference that AB says would be considered clinically relevant.
Not only did masitinib achieved this difference in ALFRS-R at the interim, it did so with a p value of less than 0.01. According to the statistical analysis plan, this allowed testing of secondary endpoints at a p<0.05 significance level, which were met for forced vital capacity and combined assessment of function and survival. The study is expected to render final results in Q1 next year.
In the meantime, AB will open a dialogue with regulators to determine if it can file on these interim data. If it can, this will not be the only regulatory application that it ends up pursuing for masitinib this year. In February, AB confirmed plans to submit an EU registration for the treatment of the rare disease of severe smouldering or indolent systemic mastocytosis in adult patients.
This application will be based on a phase III study that showed an 11.3% difference (18.7% with masitinib compared with 7.4% with control) on the primary endpoint of cumulative 75% response rate on pruritus or flushes or depression or fatigue, with a p-value of 0.0076. That study also achieved similar, highly statistically significant differences on three secondary endpoints and on three different markers of mast cell activation.
Develop once, use many times
AB Science has shown remarkable persistence with masitinib. It has conducted a large number of studies, including a phase III study in pancreatic cancer that was the basis for an unsuccessful filing attempt in the EU. It has since initiated a confirmatory study in the same indication.
The group may hold some sort of biotech record by virtue of the fact masitinib is, according to AB's own website, currently being assessed in 22 studies, including some 11 phase IIIs, for a variety of solid tumour, liquid tumour, autoimmune and neurological indications. The word apparently has to be used here since Clinicaltrial.gov listings are available for less than half of these and many of those that do appear have not been updated in several years. Details of the current development schedule, as far as can be confirmed by EP Vantage, are shown in the table below.
It is possible that by mid-2017, AB could have two new human indications approved for masitinib, which is already available in the EU for the veterinary application of canine mast cell tumors. The drug received a conditional approval for veterinary applications in the US, but this was withdrawn at the end of last year. Given the commercial and pricing complexities AB will undoubtedly have to face with a drug approved in different indications, not having a veterinary version available – at least in the US – might be considered a blessing.
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