A clear transdermal cannabinoid (CBD) gel (ZYN002, Zynerba Pharmaceuticals) improved key symptoms of fragile X syndrome in the phase 2 FAB-C study, the company reports.
Topline results of the open-label study in pediatric and adolescent patients with fragile X syndrome show that ZYN002 met its primary endpoint, having achieved a 46% improvement (P < .0001) in the total score of Anxiety, Depression, and Mood Scale (ADAMS) at week 12 compared to baseline.
ZYN002 also achieved clinically meaningful improvements in all measures of the Aberrant Behavior Checklist for Fragile X (ABC-FXS), which addresses the key symptoms of fragile X syndrome, including social avoidance, temper tantrums, repetitive movements, and hyperactivity.
According to the company, ZYN002 is the first and only pharmaceutically produced CBD formulated as a permeation-enhanced gel.
“This is a very difficult patient population, and we’re thrilled with the data. It gives us a step to now go forward and speak with the FDA and hopefully be in pivotal trials sometime in 2018,” Armando Anido, Zynerba’s chairman and chief executive officer, told Medscape Medical News.
The FAB-C study included 20 patients aged 6 to 17 years who had fragile X syndrome. The diagnosis was confirmed by molecular documentation of full mutation in the fragile X mental retardation 1 (FMR1) gene. ZYN002 treatment was started at a dose of 50 mg daily; the dose could be increased to 250 mg daily for the first 6 weeks. After the initial 6 weeks of therapy, there followed by a maintenance dosing period, which lasted through week 12. The gel is rubbed on the upper arm and takes 30 to 45 seconds to dry.
The study met the primary endpoint for change from baseline to week 12 in the total score of the ADAMS scale, which has been validated in patients with fragile X syndrome.
Table 1.
| Primary Endpoint | Baseline Score | Week 12 Score | Change | Improvement |
|---|---|---|---|---|
| ADAMS total score | 33.4 | 18.1 | -14.1 | 45.8% (P < .0001) |
Treatment with ZYN002 also led to improvement in scores on the general anxiety, social avoidance, compulsive behavior, manic/hyperactive behavior, and depressed mood subscales of the ADAMS.
Table 2.
| ADAMS Subscales | Baseline | Week 12 | Change | Improvement |
|---|---|---|---|---|
| General anxiety | 10.0 | 4.6 | -4.8 | 54.0% (P < .0001) |
| Social avoidance | 10.2 | 4.8 | -5.1 | 52.9% (P = .0002) |
| Compulsive behavior | 2.8 | 1.4 | -1.2 | 50.0% (P = .0262) |
| Manic/hyperactive | 9.4 | 6.1 | -2.7 | 35.1% (P = .0003) |
| Depressed mood | 2.8 | 2.0 | -0.9 | 28.6% (P = .1417) |
Topline data were also positive for multiple secondary endpoints, including the ABC-FXS, Clinical Global Impression of Improvement (CGI-I), the Pediatric Anxiety Rating Scale (PARS-R), Visual Analogue Scales for Anxiety, Hyperactivity and Tantrum/Mood Lability, the Vineland Adaptive Behavior III, a quality of sleep measurement, and the Pediatric Quality of Life (PedsQL). “The results of the secondary endpoints reinforce the results demonstrated in the ADAMS,” the company said.
ZYN002 was well tolerated, with a safety profile consistent with previously released data from clinical trials, the company said. There were no severe adverse events and no drug-related gastrointestinal events, and no tetrahydrocannabinol (THC) was detected in plasma. Thirteen patients have enrolled in the open-label extension study.
“The symptoms of fragile X can be overwhelming to a patient and caregiver, so I’m very enthusiastic about the responses to ZYN002 that we saw during this study,” Honey Heussler, MBBS, of Children’s Health Queensland and lead investigator in the FAB-C study, said in the release. “These data are extremely promising, particularly the improvements in anxiety, social avoidance, and irritability as measured by scales including ADAMS, ABC-FXS, and PARS-R. Tolerability is essential in these patients, so I’m very pleased to see that ZYN002 was well tolerated in fragile X patients.”
Zynerba is also evaluating the use of cannabinoid gel in adult epilepsy patients who have focal seizures and for knee pain due to osteoarthritis.
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