Bristol Myers Squibb (BMS) has recently secured approval from the US FDA for Cobenfy (xanomeline and trospium chloride) for the treatment of adults with schizophrenia. Cobenfy has a mechanism of action (MOA) distinct from traditional antipsychotics. However, as the drugs most widely used to treat schizophrenia are inexpensive, genericized atypical antipsychotics, the schizophrenia market is competitive and crowded. This could make it difficult for Cobenfy to penetrate the market, according to GlobalData, a leading data and analytics company.
For over 60 years, the dopaminergic hypothesis of schizophrenia has formed the basis of the schizophrenia treatment paradigm, whereby atypical antipsychotics target the abnormally elevated concentration of dopamine through the 5-HT2A receptors and dopamine D2 receptors. As the atypical antipsychotics have the same MOA, and therefore a similar efficacy profile, differentiated only by slight nuances in their safety profiles, patients who do not respond well to atypical antipsychotics have limited options to manage their schizophrenia symptoms.
Christie Wong, Managing Neurology Analyst at GlobalData, comments: “Cobenfy unlocks the first new drug class for schizophrenia with a novel MOA to be approved in decades. It is a coformulation of a muscarinic acetylcholine M1 and M4 receptor agonist, xanomeline, and peripheral muscarinic acetylcholine antagonist, trospium chloride, and does not directly modulate dopaminergic or serotonergic transmission.”
Cobenfy has been generally well tolerated in clinical trials, and unlike the atypical antipsychotics, it does not have a boxed warning of increased mortality in elderly patients with dementia-related psychosis or suicidal thoughts and behaviors with concomitant antidepressant drug usage.
Wong adds: “However, as numerous atypical antipsychotics and their generics dominate the schizophrenia market and are very well-entrenched in the treatment algorithm, it is unlikely that Cobenfy will immediately change prescriber habits and replace atypical antipsychotics as a first-line treatment option. Instead, Cobenfy could be an option for patients who have a partial response to atypical antipsychotics or those who cannot tolerate the side effects of weight gain, sedation, and movement disorders associated with atypical antipsychotics.”
It is unclear whether there will be a restriction in reimbursement by payers for Cobenfy. BMS has proposed an annual cost of therapy (ACOT) of $22,500 for Cobenfy. This a significant premium compared to generic oral aripiprazole which has an average ACOT of $540. It is likely that payers will require failure on at least one cheaper atypical antipsychotic before Cobenfy is reimbursed.
Key opinion leaders (KOLs) previously interviewed by GlobalData noted that while Cobenfy has demonstrated a large reduction in Positive and Negative Syndrome Scale (PANSS) score against placebo in the EMERGENT pivotal trials, there is no data on the efficacy of Cobenfy against an active comparator like an atypical antipsychotic.
A head-to-head study comparing the efficacy, safety, and treatment adherence of Cobenfy and an atypical antipsychotic could help differentiate Cobenfy, change prescriber habits, and reassure health economists about Cobenfy’s cost-effectiveness compared with established atypical antipsychotics.
Cobenfy is also being investigated as an adjunctive therapy in patients who have an inadequate response to atypical antipsychotic monotherapy in an ongoing Phase III ARISE trial (NCT05145413). If positive results are found in the ongoing ARISE trial, Cobenfy could be the first approved adjunctive therapy for the treatment of the positive and negative symptoms of schizophrenia.
Wong concludes: “BMS’s Cobenfy is likely to have the first-to-market advantage in both the monotherapy setting and as an adjunctive treatment if it receives approval.”
