The US Food and Drug Administration (FDA) have approved Abbott’s supplemental New Drug Application (sNDA) for Lupron Depot-PED (leuprolide acetate for depot suspension). The one-month formulation is the first product in its class to include long-term data in its label for the treatment of central precocious puberty (CPP), a condition which causes children to enter puberty too soon. The prescribing information now contains 18 years of data, including pre-specified outcome results on puberty, height and reproductive function.
"Guiding a child through puberty can be a challenge for any parent, but when things go awry in the body and this process happens too soon, it can be worrisome for everyone," said John Leonard, M.D., senior vice president, Global Pharmaceutical Research and Development, Abbott. "This study provides patients and physicians with important information to better understand Lupron Depot-PED for 1-month administration and its long-term impact, particularly on reproductive function and normalized adult height."
Abbott's submission was supported by an open-label study that enrolled 55 patients (mean age 7 ±2 years) in a treatment phase. Patients were assessed for signs and symptoms of puberty, a particular hormone (called LH), height and reproductive function. During treatment, clinical signs and symptoms of puberty were suppressed and normalized growth rates were achieved in most patients.
Forty children continued in the post-treatment follow-up period. Six months after treatment stopped, puberty resumed and 87.9 percent of patients achieved LH levels in the puberty range. Thirty-three subjects were observed until they achieved final or near final adult height. Results showed that patients experienced an average height gain over predicted adult height before treatment. In a post-treatment survey of 20 females (ages 18-26), 80 percent reported normal menstrual cycles, and seven of these females reported pregnancies.
An increase of CPP signs and symptoms were seen in the first four weeks of treatment in some patients, but resolved over time. The most common side effects reported during treatment in this study were sore throat, headache, flu syndrome and rash, injection site pain, moodiness and hot flushes.
CPP is a condition that causes children to enter puberty too soon, resulting in the development and progression of secondary sex characteristics such as breast development in females and genital development in both males and females and can potentially lead to a diminished adult height. This occurs in one child of every 5,000 to 10,000 children and is more common in girls. By definition, CPP starts in girls under the age of 8 and boys under the age of 9.
During puberty, the brain produces a hormone called gonadotropin-releasing hormone (GnRH). Through a complex process, GnRH causes increases in other hormones like luteinizing hormone (LH) and follicle stimulation hormone (FSH). It is these hormones that cause the ovaries to produce estrogen and the testicles to produce testosterone.
Lupron Depot-PED works by suppressing the level of hormones that cause puberty. This decrease in the production of certain hormones delays premature puberty until a more appropriate time in the child's life.