An innovative clinical trial of previously incarcerated adult schizophrenia patients designed by Johnson & Johnson's ($JNJ) Janssen Pharmaceuticals concluded that by improving medication adherence, the company's blockbuster, once-a-month injectable for schizophrenia results in better outcomes than daily oral competitors, as measured by real-world (as opposed to strictly clinical) outcomes like arrest or psychiatric hospitalization.
Of the more than 400 subjects in a 15-month study, less than 40% of patients on J&J's Invega Sustenna had a treatment failure, compared to nearly 54% of those receiving one of 7 oral meds for the psychiatric condition. In addition, those on the injectable went longer before experiencing their first treatment failure; their median time to treatment failure was 416 days, compared to 226 days for the oral medication group.
That's good news for a drug that already earned $1.5 billion in 2014. Janssen is in discussions with the FDA about adding data from the trial into Invega Sustenna's labeling, and the new information strengthens the case for the three-month dosing option, which is under FDA review.
The study defined treatment failure as "arrest/incarceration, psychiatric hospitalization, suicide, discontinuation of antipsychotic treatment due to inadequate efficacy, treatment supplementation with another antipsychotic due to inadequate efficacy, discontinuation of antipsychotic treatment due to safety or tolerability concerns, or an increase in the level of psychiatric services to prevent imminent psychiatric hospitalization."
The most common causes for treatment failure were arrest/incarceration or psychiatric hospitalization. The rate of hospitalization or reincarceration was 33.6% in the injectable group compared to 45% in the oral group. Other causes of treatment failure included discontinuation of antipsychotic treatment or treatment supplementation due to poor efficacy, as well as an increase in the level of psychiatric services to prevent imminent psychiatric hospitalization.
J&J says extra efforts were made to include subjects who are typically excluded from clinical trials. In fact, a previous incarceration and release from custody within 90 days of the screening visit were requirements for participation in the trial.
"Across the U.S., seriously mentally ill persons, including persons with schizophrenia, are three times more likely to be in jail or prison versus being in a hospital, creating a large and costly problem for the U.S. healthcare system," said one of the trial's investigators, Dr. Jason Bermak, in a statement. "This study addresses the fact that the lack of consistent treatment can put patients at risk for relapse, possibly leading to incarceration, hospitalization and other serious consequences. However, with proper treatment and support, individuals living with schizophrenia can and do live meaningful lives."
The study authors attribute the better outcomes among patients on the injectable to improved patient adherence. More than 95% of patients in the Invega Sustenna group had satisfactory adherence to the recommended dose of one injection a month, while pharmacy refill records showed that less than one-fourth of patients on oral medications obtained their medications as recommended. The subjects were given vouchers to cover the cost of the prescription.
"In actual practice, treatment with oral antipsychotic medications requires multiple points of adherence. These include whether a clinic visit is made, whether a prescription is received, whether the prescription is filled, and, finally, whether the medication is taken as prescribed. For injectable medications, these requirements are limited to whether the patient attends a clinic visit and receives an injection," the study authors, all of whom work for or are affiliated with Janssen, write in The Journal of Clinical Psychiatry.
Previous trials comparing long-acting injectable to oral antipsychotics have produced inconsistent results, the investigators write: "We hypothesize that the inconsistencies in these reports might be a consequence of the study designs chosen for these comparisons and, possibly, a failure to follow a broad spectrum of patients using measures that reflect an adequate breadth of real-world outcomes."
They conclude that the findings "support the value of real-world study designs when attempting to identify treatment differences that may relate to formulation differences."