Agitation brought on by Alzheimer’s illness at present has one FDA-approved remedy, however that drug brings severe security dangers. An Axsome Therapeutics drug has blended outcomes from its newest slate of medical checks on this indication, however firm executives say the stability weighs in favor of the remedy they usually’re planning to take the information to the FDA.
The Axsome drug, Auvelity, is already authorised as a remedy for main depressive dysfunction. The preliminary outcomes introduced Monday are from two checks of the tablet as a remedy for Alzheimer’s agitation. In one of many research, the drug met the principle purpose by exhibiting a statistically important delay within the time to relapse. This research additionally met a key secondary purpose of stopping relapse of Alzheimer’s agitation.
The info are much less clear for the second Section 3 take a look at that posted preliminary knowledge Monday. Whereas the drug confirmed numerical enchancment on the trial’s predominant purpose, Axsome mentioned these outcomes weren’t sufficient to be statistically important. Nonetheless, the corporate factors to statistical significance achieved in two earlier Section 3 checks in Alzheimer’s agitation. With three pivotal medical trials reaching statistically important outcomes and one exhibiting numerical enchancment, the corporate mentioned it’s readying a brand new drug utility it expects to file with the FDA within the second half of 2025.
Auvelity initially gained FDA approval in 2023 as a remedy for despair, particularly main depressive dysfunction. This drug is a mix of two older drugs, the despair drug buproprion and dextromethorphan, a medicine that crosses the blood-brain barrier to focus on NMDA receptors. Dextromethorphan is often utilized in cough medication; its focusing on and blocking of NMDA receptors suppresses exercise within the mind that causes coughing. NMDA receptors are discovered all through the central nervous system and play key roles in features equivalent to studying and reminiscence. Axsome has been testing whether or not blocking these receptors also can deal with the agitation brought on by Alzheimer’s.
The first drug particularly authorised for treating Alzheimer’s agitation was Rexulti, from companions Lundbeck and Otsuka Pharmaceutical. Rexulti, which is assumed to work by affecting serotonin receptors, was initially authorised in 2015 as a remedy for each main depressive dysfunction and schizophrenia. The next yr, Rexulti was authorised as a upkeep remedy for schizophrenia. The drug’s label was expanded to Alzheimer’s agitation in 2023.
Rexulti, throughout all of its authorised indications, generated 3.8 billion Danish krone (about $530 million) in income within the first 9 months of 2024, a 15% enhance in comparison with the identical interval within the prior yr. In its monetary studies, Lundbeck attributes the income development to prescriptions for Alzheimer’s agitation. The drug has additionally acquired approvals on this indication in Australia, Israel, Malaysia, Singapore, and Switzerland.
In despair, Axsome’s Auvelity competes in a crowded market of branded and generic drugs. The drug accounted for $198.7 million in income for the primary 9 months of 2024, in accordance with the corporate’s most up-to-date monetary report. Alzheimer’s agitation represents a big market the place Rexulti could be Auvelity’s solely competitor. However the Axsome drug has the chance to supply a security edge.
Rexulti’s label carries a black field warning for increased dangers of suicidal ideas and behaviors, which is according to different atypical antipsychotics. Throughout Auvelity’s Section 3 research, Axsome says its drug was secure and properly tolerated within the aged research individuals. Moreover, Auvelity was not related to elevated threat of falls, cognitive decline, or sedation and there have been no deaths reported in sufferers who acquired the research drug.
The black field warning for Rexulti is a major limiting issue to be used of the drug in aged sufferers, William Blair analyst Myles Minter wrote in a notice despatched to buyers on Monday. Axsome’s Auvelity may differentiate itself with a distinct mechanism of motion that doesn’t introduce the identical harmful security dangers as Rexulti.
“We stay bullish on approval prospects and imagine Axsome sustaining breakthrough remedy designation regardless of Rexulti’s approval highlights that the FDA acknowledges there stays a excessive unmet want right here regardless of authorised remedy, which ought to bode properly for Axsome from a regulatory perspective,” Minter mentioned.
The excellent query is whether or not the medical knowledge are adequate. Given the medical trial that fell in need of statistical significance, Minter mentioned the FDA might want to present regulatory flexibility towards the Axsome drug. There’s precedent for neuropsychiatry medication overcoming the failure of a pivotal research to win FDA approval primarily based on the totality of information. One instance famous by Minter is Rexulti, whose growth program in Alzheimer’s agitation resulted in two optimistic research and one adverse research.
To Leerink Companions analyst Marc Goodman, the outcomes posted Monday create probably the most confusion for Auvelity’s prospects in Alzheimer’s agitation. Of the 4 Section 3 checks of Auvelity on this indication, two had been randomized, placebo-controlled research and two had been withdrawal research. In withdrawal research, all sufferers obtain the research drug at first. However after a time frame, sufferers who present response to remedy are randomly assigned to both proceed receiving the research drug or full the trial on a placebo. Of the 2 medical trials posting knowledge Monday, the withdrawal research is the one which met its purpose.
Goodman mentioned it’s unclear how the FDA will view the Auvelity withdrawal research. He added that Leerink expects an FDA advisory committee will likely be convened to debate the stability of the drug’s efficacy and security, and the optimistic security knowledge could sway the vote.
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