Karuna bucks the neuro trend

Psychiatry has claimed its fair share of biopharmaceutical victims. But Karuna has made light of this thorny area today, claiming an emphatic victory in the pivotal Emergent 2 trial of his novel schizophrenia project KarXT.

However, Karuna still has more long-term safety data to gather and doesn’t even expect to submit KarXT to the FDA by mid-2023. But approval seems likely, so attention will shift to whether the company can pull off a successful solo launch, with Karuna still insisting it can go it alone in the US. Still, investors might keep an eye out for a potential takeout.

These investors sent Karuna’s shares up 55% at the opening today. Group rival Cerevel was also up 17% this morning, although that company’s selective muscarine project is a long way behind with Phase 2 data due in 2024.

Exceeded expectations

There should be pent-up demand for a new class of antipsychotics, as existing drugs that target dopamine and serotonin receptors leave much to be desired.

Karuna executives spoke about the universal appeal of KarXT during a conference call today. “I can see clinicians using and prescribing this drug across the board, in every patient category out there,” said the group’s chief executive officer, Steve Paul. He cited treatment-na├»ve patients, those who responded to current antipsychotics but experienced unpleasant side effects such as weight gain, and patients who did not respond optimally to current medications.

Prior to the Emergent-2 data, some analysts had expected that KarXT would be largely reserved for non-responders to existing therapies; the current rate pharmaceuticals The sell-side consensus of $1.7 billion in sales by 2028 could therefore be due to an upgrade.

The headline results certainly look impressive. The study met its primary endpoint, change from baseline in the total Positive and Negative Syndrome Scale (PANSS) score at week five, with KarXT-treated patients experiencing a 21.2-point reduction versus a 11.6-point reduction in the placebo group showed.

That 9.6-point delta wasn’t too far from the 11.6-point difference found in the Phase 2 Emergent-1 study, and well above the seven-point difference that investors wanted to see , according to Stifel analysts.

Also impressive was the fact that Emergent-2 found a statistically significant benefit in the secondary endpoint of negative schizophrenia symptoms, which have been difficult to manage in the past.

side effects

When it comes to adverse events, especially cholinergic side effects such as nausea and vomiting, there are still some gaps to be filled. The project is a co-formulation of the muscarinic agonist xanomeline with trospium chloride, a peripheral muscarinic receptor antagonist – the idea being that trospium reverses the peripheral side effects of xanomeline but does not interfere with its action in the brain.

All Karuna says for now is that KarXT’s safety profile was consistent with previous studies, with cholinergic side effects being mild to moderate and “mostly transient in nature.”

Regarding other adverse events previously flagged as observational events, Karuna noted that Emergent-2 caused increases in blood pressure, but added that blood pressure measurements were similar to placebo.

And as in Phase 2, there were increases in heart rate, but these “decreased in magnitude by the end of the trial.”

Overall, discontinuation rates related to adverse events should be reassuring at 7% for KarXT and 6% for placebo. And KarXT was not associated with the weight gain and drowsiness seen with older antipsychotics.

The company doesn’t think it’ll need more efficacy data for its U.S. filing, but investors have almost a year to wait for news on that front.

Trials of KarXT
study Attitude status
emergence-1 Inpatients with schizophrenia compared to placebo Completed, met
emergence-2 Inpatients with schizophrenia compared to placebo Completed, met
emergence-3 Inpatients with schizophrenia compared to placebo Top line data due Q1 2023
emergence-4 Open ambulatory extension of Emergent-2 & 3 registration
emergence-5 52-week open-label outpatient study registration
Develop Outpatients with schizophrenia, in addition to the current SOC Top line data due H1 2024
Stand up Outpatients with schizophrenia, open-label extension of Arise registration
Adept-1 Alzheimer’s psychosis Beginning Q3 2022
Adept-2 Alzheimer’s psychosis start in 2023
Adept-3 Alzheimer’s Psychosis, Open Label Extension start in 2023
All Phase 3 except Phase 2 Emergent-1. Source: Company presentation, clinicaltrials.gov.

Leave a Comment

Your email address will not be published.