An old, controversial Pfizer drug shows mid-stage efficacy against narcolepsy
Reboxetine never got much traction in the US. Marketed as an anti-depressant in Europe for the past 20 years, the Pfizer drug was provisionally FDA-approved in 1999 but the agency later retracted their permission and, more recently, a German meta-analysis made the compound a prime example of translational failure. “Ineffective and potentially harmful,” the analysis concluded.
Last October, though, a small New York-based CNS biotech called Axsome announced it would try to resurrect the compound, which has always worked elegantly in mice, stateside to treat narcolepsy. Yesterday, they unveiled Phase II data showing the drug may indeed help prevent cataplexy attacks and reduce daytime sleepiness, two of the disorder’s primary symptoms.
In a study of 21 patients who alternated between 2 weeks of reboxetine and 2 weeks placebo, reboxetine reduced the frequency of cataplexy attacks by nearly 50% from their baseline. Over 2 weeks, those on the drug saw 14.6 fewer attacks per week on average, as compared with 2.6 fewer on placebo (p=0.002).
On the Epworth Sleepiness Scale – an assessment used to measure excessive daytime sleepiness (EDS) – patients on the drug saw on average a 6-point improvement, compared with 3.1 on placebo (p=0.003).. Inadvertent naps fell 31.8%, against 5.3% for placebo (p=0.038).
AXS-12, as Axsome calls it, emerged out of the company’s central nervous system program. They went public in 2015 and raised $51 million on the strength a Phase III non-opioid pain drug, AXS-02. That remains in late-stage development, along with a migraine drug and a bupropion/dextromethorphan mix being tested for smoking, Alzheimer’s agitation and two forms of depression.
In unveiling the narcolepsy program last year, Axsome cited an association between depression – reboxetine’s initial indication – and narcolepsy, although it’s not clear if that association is causal or a result of brain chemistry: i.e. can both disorders be chalked up to similar chemical imbalances or does sleep imbalance from narcolepsy lead to depression?
Axsome has not said exactly where it goes from here. The company said it’s meeting with the FDA soon, but with Phase III readouts in their prominent programs pending, it’s not clear when that will happen.