Axsome therapeutics is a clinical biopharmaceutical company focused on developing innovative therapies for central nervous system (CNS) diseases. Recently, the company announced that the phase III stride-1 study evaluating axs-05 (dextromethorphan / bupropion release regulator) in the treatment of refractory depression (TRD) has completed patient randomization. Patients diagnosed with major depression (MDD) are defined as refractory if they fail to treat two or more antidepressants
Depression (TRD). MDD is a serious disease characterized by depression or loss of interest or happiness in daily activities for at least two weeks, and impairing social, vocational, educational or other important functions. The National Institutes of Health (NIH) estimates that about 7.1% of American adults experience MDD every year. Nearly two-thirds of the confirmed and treated patients do not receive enough treatment response after receiving first-line treatment, and most patients who fail in first-line treatment will also fail in second-line treatment.
Axs-05 is a new oral NMDA receptor antagonist with multimodal activity. It is currently under clinical development for the treatment of depression and other central nervous system (CNS) diseases. Axs-05 is composed of proprietary formulations and doses of dextromethorphan and bupropion, and adopts the metabolic inhibition technology of axsome company.
Dextromethorphan component of axs-05 is a non competitive N-methyl-D-aspartate (NMDA) receptor antagonist, also known as glutamate receptor modulator, which is a new mechanism of action, which means that its effect is different from most available depression drugs. Dextromethorphan component of axs-05 is also a sigma-1 receptor agonist, nicotinic acetylcholine receptor antagonist, serotonin and norepinephrine transporter inhibitor.
The bupropion component of axs-05 can improve the bioavailability of dextromethorphan. It is a norepinephrine and dopamine reuptake inhibitor and a nicotinic acetylcholine receptor antagonist. Axs-05 has more than 30 U.S. and international patents, which are protected until 2034. In the United States, FDA has granted axs-05 breakthrough drug qualification (BTD) for the treatment of major depression (MDD) and fast track qualification (FTD) for the treatment of refractory depression (TRD).
In December 2019, axsome announced the results of the phase III Gemini study of axs-05 in the treatment of adult patients with severe MMD. The data showed that the study reached the primary end point: compared with the placebo group, the depressive symptoms in the axs-05 treatment group showed a substantial, rapid and statistically significant reduction; the total score of the Montgomery Sternberg Depression Scale (MADRS) decreased significantly compared with the baseline at the 6th week of treatment (mean reduction from baseline: 16.6 points vs 11.9 points, P = 0.002). There was also a significant improvement in all secondary endpoints.
In the treatment of depression, Johnson antidepressant Spravato (esketamine nasal spray) is the first new antidepressant drug that has been approved for more than 30 years. In the United States and the European Union, Spravato was approved in March 2019 and December respectively, combined with oral antidepressants to treat adults with refractory depression (TRD).
At present, spravato’s application for expanded indications is under review by us and European regulators: as an acute short-term therapeutic drug, it is used in combination with oral antidepressants for severe depression (MDD) with moderate to severe depressive episodes and suicidal ideation Adult patients, rapid reduction of depressive symptoms. If approved, spravato will become the first drug for patients with serious diseases usually excluded from antidepressant treatment research.
MDD patients assessed as having an imminent risk of suicide constitute a mental emergency requiring immediate intervention. Although currently available antidepressants are effective in the treatment of depression, they usually take several weeks (4-6 weeks) To achieve the full effect. This delay is potentially dangerous, especially because the risk of suicide is highest in the early stage of treatment. Compared with standard oral treatment drugs, intranasal administration of spravato can provide the advantage of rapid onset of effect.
The active pharmaceutical component of spravato is esketamine, which is a non competitive and subtype non selective activity dependent N-methyl-D aspartic acid (NMDA) Receptor antagonist has a new and unique mechanism of action, and its principle of action is different from other drugs for the treatment of depression on the market.
NMDA receptor is a subtype of ionic glutamate receptor, which plays a key role in synaptic plasticity and information exchange between neurons. In depression, it is considered that blocking NMDA receptor can improve brain plasticity Sex and enhance synaptic connections.