The psychiatry space has taken its fair share of biopharma casualties. But Karuna made light work of this tricky field today, claiming an emphatic victory in the pivotal Emergent-2 study of his new schizophrenia project KarXT.
However, Karuna still needs to collect more long-term safety data and doesn’t even expect to submit KarXT to the FDA until mid-2023. But approval seems likely, so attention will shift to whether the company can make a launch of successful solo, with Karuna still insisting she can go solo to the US. However, investors may have an eye on a potential acquisition.
These investors sent Karuna shares up 55% at today’s open. Group rival Cerevel also jumped 17% this morning, although that company’s selective muscarinic project is somewhat behind, with phase 2 data due in 2024.
It has exceeded expectations
There must be pent-up demand for a new class of antipsychotics, given that existing drugs, which target dopamine and serotonin receptors, leave much to be desired.
Karuna executives talked about KarXT’s universal appeal during a conference call today. “I can see doctors using and prescribing this drug across the board, in every patient category out there,” said the group’s chief executive, Steve Paul. He cited treatment-naive patients, those who have responded to current antipsychotics but experienced troubling side effects such as weight gain, and patients who have had a suboptimal response to current drugs.
Before the Emergent-2 data, some analysts had expected KarXT to be reserved primarily for existing therapies that are not responding; the present one Rate Pharma Therefore, the sales consensus of $1.7 billion in sales by 2028 could be due for an upgrade.
The headline findings certainly look impressive. The study met its primary endpoint, the change from baseline in the Positive and Negative Syndrome Scale (PANSS) total score at week five, with KarXT-treated patients showing a reduction of 21.2 points, versus a decrease of 11.6 points. in the placebo group.
That 9.6-point delta wasn’t too far off the 11.6-point spread seen in the Emergent-1 phase 2 trial and far more than the seven-point spread investors had wanted to see, according to Stifel analysts.
Also impressive was the fact that Emergent-2 found a statistically significant benefit on the secondary endpoint of negative symptoms of schizophrenia, which have historically been difficult to treat.
Adverse events
There are still some gaps to fill in about adverse events, especially cholinergic side effects such as nausea and vomiting. 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 inhibit its effect on 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.”
As for other adverse events previously flagged as ones to watch for, Karuna noted that there were increases in blood pressure in Emergent-2, but added that blood pressure measures were similar to placebo.
And, as in phase 2, there were increases in heart rate, but these “decreased in size by the end of the trial.”
Overall, discontinuation rates related to adverse events should be reassuring, at 7% with KarXT and 6% with placebo. And KarXT was not associated with the weight gain and drowsiness seen with older antipsychotics.
The company doesn’t believe it will need more efficiency data for its U.S. filing, but investors still have nearly a year to wait for news on that front.
| KarXT Trials | ||
|---|---|---|
| TRIAL | Placing | sTATUS |
| Emergency-1 | Schizophrenia patients versus placebo | Finished, struck |
| Emergency-2 | Schizophrenia patients versus placebo | Finished, struck |
| Emergency-3 | Schizophrenia patients versus placebo | Main line data due Q1 2023 |
| Emergency-4 | Open-label outpatient extension of Emergent-2 & 3 | recording |
| Emergency-5 | 52-week open-label outpatient trial | recording |
| Arise | Schizophrenia outpatients adjunct to current SOC | The main term line data for the first half of 2024 |
| Stand up EU | Schizophrenia outpatients, open extension of Arise | recording |
| Skilled-1 | Alzheimer’s disease psychosis | To begin Q3 2022 |
| Skilled-2 | Alzheimer’s disease psychosis | To start 2023 |
| Adept-3 | Alzheimer’s disease psychosis, open extension | To start 2023 |
| All stage 3 except stage 2 Emergency-1. Source: Company presentation, clinicaltrials.gov. | ||