FDA Approves First Six-Month LAI Antipsychotic

The “long” in long-acting injectable (LAI) antipsychotics extended its reach this past fall, as the U.S. Food and Drug Administration (FDA) approved the first twice-yearly injectable of paliperidone palmitate (marketed as Invega Hafyera by Janssen). Prior to this approval, the longest coverage offered by an LAI was three months.

“This twice-yearly injectable enables us to provide more continuous medication coverage than ever before, while further reducing self-stigma among schizophrenia patients,” said Dean Najarian, Pharm D., an associate field director for Neuroscience Medical Affairs at Janssen. “Fewer injections each year means fewer trips to the mental health clinic just for medication, fewer instances of families asking patients if they took their daily antipsychotic, and fewer reminders overall that someone has an illness.”

The FDA approval was based on data from a large phase 3 study comparing the safety and efficacy of three-month paliperidone with six-month paliperidone. Over 700 adults with schizophrenia who were clinically stable and already taking one- or three-month paliperidone were randomized to receive 12 months of either the three-month or six-month formulation. The participants’ symptoms were measured throughout the study using the Positive and Negative Syndrome Scale (PANSS) as well as other measures of functioning. Patients were considered to have relapsed if PANSS total scores or specific PANSS items rose over two consecutive assessments and/or if they had any events of psychiatric hospitalization, self-injury, violent behavior, and/or suicidal/homicidal ideation. Outcomes between the two groups were comparable, with 92.5% of the patients treated with the six-month LAI and 95% treated with the three-month LAI remaining relapse-free after one year.

The safety profile of the six- and three-month LAI was also similar in terms of the frequency and type of treatment-related side effects. The most common side effects in patients were upper respiratory tract infections, injection site reactions, and weight gain.

Najarian said he hopes that these robust relapse findings can help change the paradigm on when to use LAI antipsychotics with patients. “Right now, the average patient is 38 years old and has tried four oral medications before injectables are even discussed,” he said. “Rather than reserve LAIs for people who have experienced multiple relapses, let’s use them to delay time to relapse in the first place.”

John Lauriello, M.D., the Daniel Lieberman Professor and Chair of Psychiatry at Thomas Jefferson University, said that he believes the arrival of a six-month injectable represents significant progress in the research and development of LAIs. “It’s great that we have extended the injectable lifespan [of LAI antipsychotics] from two weeks to six months in less than two decades,” he said. “However, I would not describe the new formula as a game changer; it’s more of a graduation program for those already taking an LAI.”

Lauriello noted that many patients will not respond to or tolerate paliperidone, so this is not an option for them. Also, the six-month paliperidone formulation is only recommended for patients who are stable on one-month or three-month paliperidone formulations, not patients needing acute stabilization of their psychotic symptoms.

Jeffrey Lieberman, M.D., the Lawrence C. Kolb Professor and Chair of Psychiatry at Columbia University, agreed that the potential impacts of the six-month injectable are likely to be modest. “The longer duration adds a convenience factor, so it will benefit remote individuals, those with limited health care access, and people who do not like injections,” he told Psychiatric News. “But while the clinical data show the six-month injection is not inferior to the three-month one, there is no indication that it is any better.”

Lauriello believes the added stability offered by a twice-yearly injection could be beneficial for some patients, and he hopes Janssen or insurance groups offer pricing incentives to encourage expanded use of both three- and six-month formulations. He also believes Invega Hafyera and other LAIs would be more widely used if they could be administered at home, currently by a visiting nurse but possibly family members or even the patient themselves.

“We let patients self-inject a lot of powerful drugs like insulin; if we could feel comfortable putting antipsychotic injections in patient hands that may make them feel more a part of their treatment and more time can be spent with other aspects of care like psychotherapy or occupational therapy.”

Neither Lauriello or Lieberman were involved with the development of Invega Hafyera and do not report any existing conflicts with Janssen. ■

“A Randomized, Double-Blind, Multicenter, Noninferiority Study Comparing Paliperidone Palmitate 6-month Versus the 3-month Long-Acting Injectable in Patients With Schizophrenia” is posted here.