MIT’s Once-a-Week Pill Could Revolutionize Schizophrenia Treatment

For many people living with schizophrenia, other psychiatric conditions, or chronic illnesses like hypertension and asthma, taking medication every day can be challenging. To address this issue, MIT researchers have developed a pill that can be taken once a week, gradually releasing medication from the stomach. The findings were published in Lancet Psychiatry.

In a phase 3 clinical trial led by MIT spinout Lyndra Therapeutics, the researchers tested the once-weekly pill using a commonly prescribed medication for managing schizophrenia symptoms. They found that the weekly treatment maintained steady drug levels in patients’ bodies and was just as effective at controlling symptoms as the traditional daily dosage.

“We’ve converted something that has to be taken once a day to once a week, orally, using a technology that can be adapted for a variety of medications,” says Giovanni Traverso, an associate professor of mechanical engineering at MIT, a gastroenterologist at Brigham and Women’s Hospital, an associate member of the Broad Institute, and an author of the study. “The ability to provide a sustained level of drug for a prolonged period, in an easy-to-administer system, makes it easier to ensure patients are receiving their medication.”

Traverso’s lab began working on the ingestible capsule used in this trial more than a decade ago, as part of a broader effort to make medications easier for patients to take. The capsule is about the size of a multivitamin and, once swallowed, it expands into a star shape that allows it to stay in the stomach until the full dose of medication has been released.

Richard Scranton, chief medical officer at Lyndra Therapeutics, is the senior author of the paper. Leslie Citrome, a clinical professor of psychiatry and behavioral sciences at New York Medical College School of Medicine, is the lead author. Nayana Nagaraj, medical director at Lyndra Therapeutics, and Todd Dumas, senior director of pharmacometrics at Certara, are also listed as authors.

Over the past ten years, Traverso’s lab has developed several types of capsules that can be swallowed and stay in the digestive tract for extended periods, slowly releasing medication over days or weeks. In 2016, the team introduced a star-shaped device, which Lyndra later advanced into clinical trials for patients with schizophrenia.

The device contains six arms that can be folded in, allowing it to fit inside a capsule. The capsule dissolves when the device reaches the stomach, allowing the arms to spring out. Once the arms are extended, the device becomes too large to pass through the pylorus (the exit of the stomach), so it remains freely floating in the stomach as drugs are slowly released from the arms. After about a week, the arms break off on their own, and each segment exits the stomach and passes through the digestive tract.

For the clinical trials, the capsule was loaded with risperidone, a commonly prescribed medication used to treat schizophrenia. Most patients take the drug orally once a day. There are also injectable versions that can be given every two weeks, every month, or every two months, but they require administration by a health care provider and are not always acceptable to patients.

The MIT and Lyndra team chose to focus on schizophrenia in hopes that a drug regimen that could be administered less frequently, through oral delivery, could make treatment easier for patients and their caregivers.

“One of the areas of unmet need that was recognized early on is neuropsychiatric conditions, where the illness can limit or impair one’s ability to remember to take their medication,” Traverso says. “With that in mind, one of the conditions that has been a big focus has been schizophrenia.”

The phase 3 trial was coordinated by researchers at Lyndra and enrolled 83 patients at five different sites around the United States. Forty-five of those patients completed the full five weeks of the study, in which they took one risperidone-loaded capsule per week.

Throughout the study, the researchers measured the amount of drug in each patient’s bloodstream. Each week, they found a sharp increase on the day the pill was given, followed by a slow decline over the next week. The levels were all within the optimal range, and there was less variation over time than is seen when patients take a pill each day.

Using an evaluation known as the Positive and Negative Syndrome Scale (PANSS), the researchers also found that the patients’ symptoms remained stable throughout the study.

“One of the biggest obstacles in the care of people with chronic illnesses in general is that medications are not taken consistently. This leads to worsening symptoms, and in the case of schizophrenia, potential relapse and hospitalization,” Citrome says. “Having the option to take medication by mouth once a week represents an important option that can assist with adherence for the many patients who would prefer oral medications versus injectable formulations.”

Side effects from the treatment were minimal, the researchers found. Some patients experienced mild acid reflux and constipation early in the study, but these did not last long. The results, showing effectiveness of the capsule and few side effects, represent a major milestone in this approach to drug delivery, Traverso says.

“This really demonstrates that what we had hypothesized a decade ago, which is that a single capsule providing a drug depot within the GI tract could be possible,” he says. “Here what you see is that the capsule can achieve the drug levels that were predicted, and also control symptoms in a sizeable cohort of patients with schizophrenia.”

The investigators now hope to do larger phase 3 studies before applying for FDA approval of this delivery approach for risperidone. They are also preparing for phase 1 trials using this capsule to deliver other drugs, including contraceptives.

“We are delighted that this technology which started at MIT has reached the point of phase 3 clinical trials,” says Robert Langer, the David H. Koch Institute Professor at MIT, who was an author of the original study on the star capsule and is a co-founder of Lyndra Therapeutics.

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