Just five months after its stock market debut, Karuna Therapeutics has seen its value leap to more than $1bn on the back of a mid-stage trial of schizophrenia candidate KarXT.
Shares in the Boston-based biotech leaped more than 440% after the news of the positive trial emerged, rising from a little over $17 to $96, and Karuna promptly announced plans for a stock offering of 2.6 million shares to help fund phase 3 development of the drug.
In the trial, KarXT (xanomeline/trospium chloride) given on its own was able to tackle the psychotic symptoms of schizophrenia – as measured by the widely-used Positive and Negative Syndrome Scale (PANSS), with a ‘statistically significant and clinically meaningful’ 11.6-point improvement compared to placebo. That level compares well with current schizophrenia drugs.
Moreover, it was less likely to cause common side effects such as sedation, weight gain and ‘extrapyramidal’ effects like tremor, slurred speech and anxiety, that can seriously limit the clinical effectiveness of current antipsychotic drugs, most of which have been in use for decades.
The treatment discontinuation rate with KarXT in the study was 20%, similar to placebo, and more than 90% of patients treated with the drug were able to escalate to the highest dose. The most common side effects were constipation, nausea, dry mouth, dyspepsia and vomiting.
If that clinical profile is confirmed in phase 3 testing, KarXT could become a new, first-in-class treatment for psychosis after years of stagnation in drug development that means most patients with schizophrenia are still treated with old, generic therapies.
KarXT combines a central nervous system-acting muscarinic agonist (Eli Lilly-developed xanomeline) – which aims to tackle the psychosis symptoms – with a muscarinic receptor antagonist (trospium) that can’t penetrate the CNS but prevents unwanted side effects on peripheral nerves.
Karuna’s chief executive Steve Paul said on a conference call that the efficacy was impressive given that KarXT was given as a monotherapy, so there is also scope to see if it can be used in combination with existing atypical antipsychotic drugs that target dopamine and serotonin, such as aripiprazole, risperidone and olanzapine.
Those drugs were all big-selling blockbusters at their peak despite modest efficacy, and with schizophrenia affecting more than 21 million people worldwide it’s easy to see why investors are excited by the prospect of a potential new, first-in-class therapy.
It’s worth noting that KarXT had significant impact on PANSS subscales focusing on positive symptoms (delirium, hallucinations etc) as well as negative symptoms (social withdrawal, apathy etc). The latter group is poorly addressed with current schizophrenia drugs.
“Following our anticipated end-of-phase 2 meeting with the FDA in the second quarter of 2020, we will work to initiate a phase 3 clinical trial of KarXT in patients with schizophrenia by the end of 2020,” said Karuna’s chief medical officer Stephen Brannan.
The company is also testing the drug for psychosis in Alzheimer’s disease and pain, with new data due next year.