Weekly Schizophrenia Remedy Promises More Freedom And Adherence

Scientists have created a capsule that needs to be taken only once a week to treat schizophrenia. Inside the stomach, it opens and releases the medicine gradually, maintaining its effect for several days. This helps those who have difficulty remembering to take their medicine every day and can prevent relapses. The results showed that it works as well as the daily pill and has few side effects.

Schizophrenia is a chronic mental disorder that can cause hallucinations, delusions, difficulties in thinking and changes in behavior. To keep symptoms under control, it is essential that patients take their medication correctly and regularly.

However, in practice, many people with schizophrenia forget or have difficulty following the treatment daily, which can lead to worsening symptoms, relapses and even hospitalizations.

To try to solve this problem, scientists have developed a new capsule called LYN-005, which needs to be taken only once a week, but keeps the medicine working in the body for several days.

This capsule contains a special device, created by researchers at MIT in partnership with the company Lyndra Therapeutics. When a person swallows the capsule (which is about the size of a multivitamin), it dissolves in the stomach and releases a small, star-shaped device with six folding arms.

These arms open inside the stomach, making the device too large to exit through the stomach outlet (the pylorus). So it stays there for about a week, gradually releasing risperidone, which is the drug used to control schizophrenia.

After releasing all the medication, the device breaks into smaller pieces that are eliminated naturally by the digestive system.

The ingestible capsule is about the size of a multivitamin and, once swallowed, expands into a star shape, which helps it stay in the stomach until all of the medication has been released.

To see if this new form of drug delivery was safe and effective, researchers conducted a phase 3 study involving 83 people with schizophrenia or schizoaffective disorder.

These participants were clinically stable and remained hospitalized in specialized centers in the United States for five weeks, except for a few days when they were allowed to be away.

During the study, they received five weekly doses of the new LYN-005 capsule, plus a small daily dose of risperidone only for the first week to help them adjust. Scientists closely monitored the amount of drug in their blood (pharmacokinetics) and its effects on symptoms.

The results showed that the weekly capsule was able to maintain risperidone levels in the blood within the range considered ideal for controlling symptoms, similar to what happens when a person takes a traditional pill every day.

In addition, the patients remained clinically stable throughout the study. There were also fewer variations in the level of the medication throughout the week, which is important to ensure more consistent treatment.

The side effects observed were generally mild, with the most common being related to the gastrointestinal system, such as acid reflux and constipation, especially at the beginning of treatment.

Only one more serious case was recorded, and there were no unexpected signs of health risk. This result was considered an important milestone in the search for forms of treatment that are easier and more practical for patients.

Nowadays, in addition to daily tablets, there are injectable forms of risperidone that can be administered every two weeks, monthly or every two months, but these need to be administered by healthcare professionals and are not always satisfactory to patients.

The new capsule offers an oral option (i.e., one that the patient can take themselves) that maintains the effect for a long time, which can greatly help with adherence to treatment, especially for those who prefer to avoid injections or have difficulty remembering to take the medication every day.

The researchers now intend to conduct larger studies to confirm these results and seek approval from the FDA (US regulatory agency). In addition, they are already planning to test this technology with other medications, such as contraceptives.

Giovanni Traverso, associate professor of mechanical engineering at MIT, gastroenterologist at Brigham and Women's Hospital, associate member of the Broad Institute and author of the study. Credit: Adam Glanzman

READ MORE:

Long-acting oral weekly risperidone (LYN-005) for schizophrenia in the USA (STARLYNG-1): a multicentre, open-label, non-randomised phase 3 trial

Leslie Citrome, Nayana Nagaraj, Giovanni Traverso, Todd Dumas and Richard Scranton

The Lancet Psychiatry, Volume 12, Issue 7, 504 - 512

DOI: 10.1016/S2215-0366(25)00135-X

Abstract:

Medication non-adherence and insufficiently managed disease worsen outcomes in people with schizophrenia. We aimed to compare the bioavailability of a long-acting oral weekly formulation of risperidone, LYN-005, with daily oral risperidone at steady state. In this open-label, non-randomised, phase 3 trial, clinically stable participants with schizophrenia or schizoaffective disorder were enrolled from five sites across the USA while residing in an inpatient facility for 5 weeks (with the exception of days 9–13). After a 7-day run-in period with immediate-release risperidone (2 mg or 6 mg), participants received five doses of long-acting oral weekly LYN-005 (15 mg or 45 mg, respectively), with a supplemental half dose of daily immediate-release risperidone during week 1. Primary endpoints compared pharmacokinetic parameters of LYN-005 (minimum concentration [Cmin] at weeks 1 and 5, and maximum concentration [Cmax] and average concentration [Cavg] at week 5) with those of immediate-release risperidone on the last day of the run-in period. Prespecified primary endpoint criteria were geometric mean ratios for Cmin at week 1 and week 5 (90% CI ≥0·8), Cmax at week 5 (90% CI ≤1·25), and Cavg at week 5 (0·8 ≤90% CI ≤1·4). No people with lived experience were involved in the study design. This study was registered with ClinicalTrials.gov, NCT05779241, and has been completed. Between April 13, 2023 and Dec 1, 2023, 83 participants were enrolled in the study (62 [75%] male and 21 [25%] female; 67 [81%] Black or African American, mean age 49·3 years [SD 11·5]), of whom 47 participants completed the 5-week study. In the pharmacokinetic analysis (n=44), sustained release of the active moiety was observed across all doses of LYN-005. Geometric mean ratios of LYN-005 versus immediate-release risperidone were 1·02 (90% CI 0·93–1·12) for Cmin at week 1, and 1·04 (90% CI 0·87–1·23), 0·84 (0·77–0·92), and 1·03 (0·93–1·13) for Cmin, Cmax, and Cavg, respectively, at week 5 and met predetermined criteria. In individuals taking LYN-005 (n=67), gastrointestinal treatment-emergent adverse events were most common (44 [66%] participants), with one serious treatment-emergent adverse event reported. Weekly LYN-005 provided sustained release of risperidone at therapeutic concentrations with similar bioavailability to immediate-release risperidone. Patients remained clinically stable and no unexpected safety signals emerged. This offers a novel long-acting oral drug delivery technology for schizophrenia and schizoaffective disorder.