A new drug is being hailed as a breakthrough for the 2.8 million American adults (among 24 million people worldwide) who battle schizophrenia.

The US Food & Drug Administration (FDA) has greenlit Bristol Myers Squibb’s Cobenfy, reportedly making it the first major new treatment for the disorder in 70 years.

Unlike other antipsychotic drugs, Cobenfy appears to alleviate schizophrenic delusions without the side effects—drowsiness, weight gain, muscle jerking—that drive some patients to discontinue them.

Although Cobenfy does have its own adverse effects, including nausea, vomiting, and constipation, Bristol Myers Squibb doesn’t seem worried that those will discourage use: the company not only paid $14 billion earlier this year to buy the firm that invented the drug, it’s also testing its efficacy against psychosis from Alzheimer’s, for which there is no FDA-approved treatment.

Effectiveness against just schizophrenia would be a milestone. The disorder’s precise causes are a mystery, seemingly striking those predisposed by a mix of factors—physical, genetic, psychological, environmental—and triggered by things like stress and drug use.

Experts divide schizophrenia’s symptoms into “positive” ones, such as hallucinations and delusions, and “negative” ones that include withdrawal from, and lack of interest in, social interactions and their surroundings.

Researchers say the condition can take a physical and social toll: the disorder has been tied to early death and still carries a stigma that can lead to discrimination and homelessness.

Two Boston University Sargent College of Health & Rehabilitation Sciences psychologists who study schizophrenia are excited about Cobenfy’s potential—with a few caveats.

Here, Kim Mueser, a professor of occupational therapy and coauthor of Coping With Schizophrenia: A Guide for Families (New Harbinger Publications, 1994), and Daniel Fulford, an associate professor of occupational therapy who codeveloped an app to collect real-time social data on patients with the disorder, explain what the drug’s approval might mean for patients and whether the hype is overblown:

Q

The CEO of the Schizophrenia & Psychosis Action Alliance called Cobenfy “game-changing, potentially.” Is that hyperbole?

A

Fulford: Potentially, sure. The data so far do not suggest the drug is game-changing from an efficacy standpoint, [but] that there are significant reductions in overall symptoms, including both typical symptoms of psychosis, like hallucinations and delusions, and symptoms like mood or anxiety. About half of the participants “responded” to the drug, which the investigators defined as at least 30% reduction in total symptoms. But assuming similar efficacy relative to existing antipsychotic medications, the key benefit that might suggest this is game-changing would be perhaps less debilitating side effects with similar efficacy.

Mueser: I think that advocate is essentially correct, with the critical word being “potentially.” The initial results of clinical trials compare Cobenfy with a placebo and show significantly greater effects on psychotic symptoms, with some effects also found for more improvement in negative symptoms—reduced motivation and drive—and cognitive functioning: attention and concentration, memory, etc. FDA approval is for the treatment of psychotic symptoms. The greater improvement in negative symptoms and cognitive functioning is intriguing, since no antipsychotics have established beneficial effects in these domains.

However, the current studies of Cobenfy are very limited, in that there are no published, head-to-head comparisons with other antipsychotic medications. So we don’t know whether it is more effective than what is currently available. In addition, research is needed to evaluate whether particular subgroups of patients with schizophrenia may benefit more from Cobenfy than traditional antipsychotics, or whether combining the two types of medication is more beneficial for some patients than either one alone.

Although having multiple antipsychotics available has advantages in terms of choice and side-effect profile, the real game-changing question is whether Cobenfy is clinically superior to other antipsychotics on some outcomes or whether subgroups of patients can be identified who benefit more from it than other antipsychotics.

Q

How might Cobenfy benefit patients with schizophrenia?

A

Fulford: It would make sense for [prescribers] to explore with their patient whether switching to a drug that targets a novel pathway could be helpful for those not showing response to an existing antipsychotic medication. If they are currently on an antipsychotic medication that seems to be working for them, switching to a new drug may not be advised, especially if there is no clear evidence that the overall benefits on symptoms or other outcomes are substantially different for the new drug.

Mueser: Until clinical trials are conducted comparing Cobenfy with other antipsychotics, it is unknown how Cobenfy might benefit patients with schizophrenia. Clearly, if it is found, and replicated, to be more effective than other antipsychotics on any of the primary outcomes of schizophrenia—psychotic symptoms, negative symptoms, cognition—many patients stand to benefit from it.

Q

Cobenfy reportedly lacks the side effects of other drugs for schizophrenia, but comes with its own—nausea, vomiting, constipation. Might those dissuade appreciable numbers of patients from taking or sticking with the drug?

A

Mueser: The side effects of Cobenfy can be significant, but appear to happen in only 10 to 15% of patients. We don’t know anything about the persistence of these side effects, nor the extent to which they may lead to patients discontinuing the medication. More importantly, all of the other antipsychotics have problematic side effects, which do contribute to discontinuation, so the fact that Cobenfy has some side effects certainly isn’t a deal-breaker.

Fulford: The most common antipsychotic medications work on dopamine receptors [and have] a different set of side effects that can be quite significant, including sedation, movement/motor problems, and substantial weight gain. Whether the side effects associated with Cobenfy are more or less tolerable will come down to a personal choice, one informed by a risk/benefit analysis of the potential benefit of a new medication relative to the potential risks of side effects. The reported side effects of Cobenfy are not insignificant; nearly 20% of patients report nausea. Of course, the intensity of such symptoms, how debilitating they might be, would certainly impact decisions to initiate or continue using a medication.

Q

Cobenfy lists for around $22,000, but Bristol Myers Squibb says most eligible patients are covered by Medicare or Medicaid. Are you concerned about Cobenfy’s costs possibly discouraging some patients from using it?

A

Fulford: It’s not clear what this amount would cover. A full year of medication? One 30-day supply? Given most patients with schizophrenia or other serious mental illnesses have limited financial means, paying for this medication out of pocket is unlikely to be tenable, especially given the many existing antipsychotic medications covered by insurance.

Mueser: The cost of Cobenfy will certainly be an issue when it comes to whether Medicare/Medicaid and insurance companies will pay for it. [They] will likely limit uptake in prescriptions of the medication until there is strong evidence indicating its superiority over other antipsychotics on improving psychotic or other symptoms, or evidence indicating specific subgroups of patients benefit more from it than other antipsychotics.

Q

Could you address Cobenfy’s significance in what I understand to have been, until now, a long, relatively fallow period for new effective schizophrenia drugs?

A

Mueser: It is the first new medication for schizophrenia that has a different mechanism of action from all of the antipsychotics previously developed. All prior FDA-approved antipsychotics developed over the past decades, beginning in the 1950s, have targeted dopamine receptors as the primary mechanism of action.

Cobenfy differs from those antipsychotics in targeting cholinergic receptors. There have been multiple attempts to develop effective antipsychotic medications for schizophrenia that target a different mechanism of action than dopamine—and efforts to do this continue—but Cobenfy is the first success story in this effort, and thus it is an important advance, even if it is not found to be superior to other antipsychotics. Hopefully, this will be the first of more antipsychotics that target mechanisms other than dopamine receptors.

Fulford: I do believe this is a significant moment in drug development for schizophrenia, given the rarity of novel pharmacological treatment developments over the last half century. But, again, we need more data to understand not only the safety and efficacy profile of this medication relative to other antipsychotic medications, but also data that helps identify specific patients for whom this class of drug may better address symptoms and other outcomes.

The development of novel medications to help those struggling with impairing symptoms of psychosis is worthy of excitement. Ultimately, a combination of medications and evidence-based psychotherapies that work best for a specific patient, as well as social and other structural supports, are needed to address the full range of difficulties that people with serious mental illnesses like schizophrenia experience in daily life.