Therapeutics and Clinical Risk Management online journal published Shinogi’s promising results from two studies on Cuvposar, the first and only FDA-approved treatment to reduce chronic severe drooling in patients ages 3-16 with neurologic conditions associated with chronic drooling.

The first study, a randomized, double-blind, placebo-controlled phase III trial, showed children ages 3-16 with problem drooling due to neurologic conditions demonstrated a significantly better response to Cuvposar (glycopyrrolate) oral solution than to placebo. The second study, a multicenter, open-label trial, evaluated the safety and efficacy of Cuvposar over 24 weeks. The majority of patients in this study were ages 3-16 with moderate-to-severe drooling.

"Chronic severe drooling is a health issue for children with neurologic disorders," said lead study investigator Robert S. Zeller, M.D., director, Blue Bird Circle Clinic for Pediatric Neurology at Texas Children's Hospital, Houston, Texas. "These studies reinforce the efficacy and safety, respectively, of Cuvposar."

After eight weeks in the first study of 38 patients, 14 of 19 patients (73.7%) in the Cuvposar group and three of 17 (17.6%) in the placebo group exhibited at least a three-point improvement on the modified Teacher's Drooling Scale (mTDS) (P=0.0011). Two of the 38 patients were older than 16 and, as such, were excluded from the results. A beneficial effect of Cuvposar was observed as early as two weeks after treatment initiation (52.6%; P=0.0007), with the proportion of responders increasing continuously through week eight. Mean improvements in mTDS score at week eight were 3.94 points in the Cuvposar group and 0.71 points in the placebo group (P<0.0001).

Statistically significant differences in the first study were observed for both the investigator and parent/caregiver global assessments of study medication.  For patients in the Cuvposar group, 84.2% of investigators and 100% of parent/caregivers agreed the treatment was worthwhile, compared with 41.2% of investigators (P=0.0140) and 56.3% of parent/caregivers (P=0.0017) of patients in the placebo group.

"Parents and caregivers of children with neurologic conditions, such as cerebral palsy, can face many challenges," said Jennifer Davidson, DO, medical director, Shionogi. "By treating the severe drooling that is often associated with these conditions, these caregivers can focus their time and resources on other aspects of their children's care."

The second study of 137 intent-to-treat patients was a multicenter, open-label trial evaluating the safety and efficacy of Cuvposar. Most patients (89%) had at least one treatment-emergent adverse event (TEAE), 47% of which were deemed related to Cuvposar, with most being mild to moderate in intensity. Several TEAEs occurred more frequently in the high (>0.2mg/kg) and middle (>/=0.1mg to </=0.2mg/kg) than in the low dose (<0.1mg/kg) group.

Of 20 patients, 14 had serious adverse events, eight while taking the study drug and six within 30 days of the last dose.  Of these 20 AEs, four were considered treatment-related: nystagmus, esophageal candidiasis, dehydration and gastrointestinal motility disorder. The most common treatment-emergent adverse events (incidence >5%) were constipation, vomiting, diarrhea, pyrexia, dry mouth, flushing and nasal congestion. Nineteen patients (13.9%) discontinued due to an AE, but no AE trend was specifically associated with discontinuation.

After 24 weeks, 52.3% of patients had a greater than or equal to three-point decrease in mTDS from baseline and were classified as responders to treatment with Cuvposar.

The percentage of the 53 non-naive patients (i.e., patients previously treated with Cuvposar) classified as responders was higher than that of the 84 naive patients.  At the end of the study, 83.5% of parents/caregivers and 85.8% of investigators rated Cuvposar as a worthwhile treatment.

Cuvposar is supplied as a cherry-flavored, liquid solution for oral administration and was FDA approved in the U.S. in July 2010 and launched commercially in April 2011.