Cellulite, or edematous fibrosclerotic panniculopathy, is a condition characterized by orange peel-like dimpling of the skin typically occurring mostly on the buttocks, thighs, lower abdomen and arms. Cellulite results primarily from the tethering of fibrous septae, composed primarily of collagen, which affects fat volume that affects 85-90% of post-pubertal women of all races. There are currently no FDA approved pharmaceutical therapies available for the treatment of cellulite.

In November 2018, Endo announced positive top-line data from two pivotal Phase 3 clinical trials, RELEASE-1 and RELEASE-2, of CCH for the treatment of cellulite. Both RELEASE-1 (p=0.006) and RELEASE-2 (p=0.002) achieved the primary endpoint of composite responder analysis demonstrating at least a 2-level composite improvement of cellulite appearance independently reported by patients and clinician on the photonumeric scales of cellulite severity.

Key secondary endpoints included both investigator and patient assessments of cellulite appearance as measured by CR-PCSS (Clinician Reported- Photonumeric Cellulite Severity Scale) and PR-PCSS (Patient Reported- Photonumeric Cellulite Severity Scale) scores, SRSS (Subject Self Rating Scale) and the Subject-Global Aesthetic Improvement Scale. Eight out of eight key secondary endpoints were achieved for RELEASE-1 and seven out of eight were achieved for RELEASE-2. CCH was well tolerated in actively treated subjects with most adverse events being mild to moderated and limited to the local injection area.

Endo has global marketing rights for CCH for the treatment of cellulite and expects to submit a BLA in the second half of 2019 and a potential commercial launch is expected in the second half of 2020.
Trial Design:

These multicenter, randomized, double-blind, placebo-controlled studies evaluated the safety and efficacy of CCH in reducing the appearance of cellulite and enrolled 840 women, 420 per trial, aged 18 years or older with moderate-to-severe buttock cellulite. Each subject received up to three treatments in which CCH, 0.84 mg per treatment area, or placebo were administered. The two treatment areas included the left and right buttock. Each treatment visit occurred approximately 21 days apart. A total of 12 injections were administered into cellulite dimples per treatment area per visit. Cellulite severity was assessed at the beginning and conclusion of treatment. The assessments were conducted by each patient and clinician using two validated photonumeric cellulite severity scales developed by Endo and third-party psychometric experts.

The primary endpoint of the studies was a composite responder analysis demonstrating at least a 2-level composite improvement on the photonumeric cellulite severity scale, independently reported by both the patient and clinician. Key secondary endpoints included the percentage of subjects that experienced at least a 1-level or 2-level improvement in patient reported assessment, percentage of subjects with a 1-level composite improvement, percentage of satisfied subjects, change from baseline in a cellulite impact scale and the percentage of subjects with at least a 1-level or 2-level improvement in the global aesthetic improvement scale (GAIS).