A novel, ultra-long-acting oral formulation of the antipsychotic risperidone (Risperdal) only needs to be taken once weekly and appears to be safe and effective, results of a new phase 2 study suggest.
The new formulation, LYN-005 (Lyndra Therapeutics), quickly reached therapeutic levels in patients, provided sustained exposure to risperidone active moiety over 7 days, and reduced peak drug exposure.
Dr David Walling
“This novel formulation has the potential to improve treatment adherence and quality of life in patients with schizophrenia or schizoaffective disorder,” study investigator David Walling, PhD, chief clinical officer for the Collaborative NeuroScience Network, Long Beach, California, told Medscape Medical News.
The findings were presented at the virtual American Society of Clinical Psychopharmacology (ASCP) 2021 Annual Meeting.
Adherence Is Key
About 50% of patients don’t take medications as prescribed, creating a significant relapse risk, Walling noted.
“Here we have the possibility of having a once-weekly oral medication, which means patients don’t have to struggle with the issue of taking the medication daily. Right now, all we have on the market for long-acting medications for schizophrenia are injectables, where the patient has to go get a shot every month or every 2 weeks in order to have the medication in their system for a longer period of time,” he added.
The study included 32 clinically stable patients with a primary diagnosis of schizophrenia or schizoaffective disorder.
Patients received immediate-release (IR) risperidone at 2 mg or 4 mg, based on their current antipsychotic dose, for 13 days.
They were then randomly assigned 3:1 to receive either IR risperidone-matched placebo and LYN-005 at 14 mg or 28 mg risperidone (12 patients per group), or to LYN-005 matched placebo and IR risperidone, 2 mg or 4 mg, (4 patients per group) for 3 weeks.
LYN-05 was administered once weekly for a total of three doses. IR risperidone was administered once daily.
The study’s primary endpoints were pharmacokinetics after LYN-005 and IR risperidone, and the incidence of adverse events.
Following LYN-005 administration, systemic exposure to risperidone active moiety (risperidone and 9-hydroxyrisperidone combined) increased with the increasing dose. Peak concentration occurred within the first 3 days of dosing and peak exposures from LYN-005 were lower than with IR risperidone.
“Steady state was achieved around day 15. It didn’t take 3 weeks of dosing for patients to achieve steady state. We achieved that around day 15,” Walling said.
LYN-005 was well tolerated in the 85% of study participants who received all three doses.
Adverse events occurred in 18 (75%) patients who received LYN-005. Of these, 10 were with the 14 mg dose, and 8 with the 28 mg dose.
The most common AEs were gastrointestinal, which occurred in 13 (54%) patients receiving LYN-005, with a higher incidence in the 28-mg group than in the 14 mg group.
Additionally, 9 patients had abdominal pain, discomfort, or tenderness, and 5 patients (21%) had nausea.
Overall, the incidence of adverse events was higher for LYN-005 compared with IR risperidone, but they were judged to be mild and transitory, with fewer AEs reported with subsequent LYN-005 dosing. After the first dose, 58% of patients reported an AE; this dropped to 18% after the third dose.
An Important Development
Commenting on the findings for Medscape Medical News, Ira D. Glick, MD, professor emeritus, Stanford University School of Medicine, Stanford, California, said, “The major problem with schizophrenia is getting adherence.”
“The better the adherence, the better the outcome, the worst the adherence, the worse the outcome, so being able to take a preparation less often is a very important advance in the field,” said Glick, who was not involved in the research
Long-acting preparations for chronic mental illness represent a significant advance, he said.
“The future of the treatment of schizophrenia is long-acting injectables. That is the trend,” Glick explained “The oral once-a-week preparation may be useful in a group of patients who are phobic about needles, but with the injections, you can be sure that the patient has received their medication. With the oral, there is more of a chance to be noncompliant.
“That said, having an effective, longer-acting oral for those who refuse injections is helpful. It’s an important development, and it’s part of the advance the whole field is moving toward, to ensure adherence to treatment. We know treatment works, we know it is going to save lives, and that’s what this ultra-long-acting formulation is promoting.”
Walling is chief clinical officer for the Collaborative NeuroScience Network, LLC, Long Beach, California. Glick has disclosed no relevant financial relationships.
American Society of Clinical Psychopharmacology (ASCP) 2021: Abstract 3002873. Presented June 2, 2021.
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