Endo International plc’s clostridium histolyticum (CCH) performed well in two identical Phase 3 studies for the treatment of cellulite in the buttocks.

Subjects receiving CCH showed highly statistically significant levels of improvement in the appearance of cellulite with treatment, as measured by the trial's primary endpoint (RELEASE-1, p=0.006 & RELEASE-2, p=0.002), which was at least a 2-level composite improvement in cellulite severity in the target buttock at Day 71 as compared to subjects receiving placebo.

In addition, RELEASE-1 passed 8 out of 8 key secondary endpoints and RELEASE-2 passed 7 out of 8 key secondary endpoints. CCH was well-tolerated in the actively-treated subjects with most adverse events (AEs) being mild to moderate in severity and primarily limited to the local injection area.

"Based on our review of the Phase 3 data, we remain confident in our CCH program for cellulite—a condition that makes many women self-conscious and prompts them to seek treatment options," says Matthew Davis, M.D., R.Ph., Endo's Senior Vice President and Chief Medical Officer, in news release. "If approved, CCH has the potential to be an important new treatment for cellulite and we are excited to take the next steps in that process."

About RELEASE-1 and RELEASE-2


RELEASE-1 and RELEASE-2 are two identical, multicenter, randomized, double-blind, placebo-controlled studies that enrolled 845 women (423 and 422 in each separate trial) aged 18 years or older in the United States with moderate to severe cellulite. Each subject received up to three treatments of CCH (0.84 mg / treatment area) or placebo with each treatment session occurring approximately 21 days apart. Up to twelve injections were administered during each session across each treatment area – the left and right buttock. At both the outset and conclusion of each treatment, cellulite severity was assessed 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 Phase 3 studies was a composite responder analysis demonstrating at least a 2-level composite improvement independently reported by both patient and clinician on the photonumeric scales of cellulite severity in the target buttock. Key secondary endpoints in target buttocks included the percentage of subjects that experience at least a 1-level or 2-level improvement in patient reported assessment percentage of subjects with a 1-level composite improvement, the percentage of subjects with at least a 1-level or 2-level improvement in the global aesthetic improvement scale (GAIS), as well as percentage of subjects with a 2-level composite improvement in non-target buttocks and also percentage of satisfied subjects, change from baseline in a cellulite impact scale (i.e., patients' self-perception related to their cellulite).

"The Phase 3 results are positive for patients and consistent with previous data that demonstrate CCH has the potential to be a breakthrough treatment for cellulite, a condition that millions of women experience but for which there are currently limited effective treatment options," says Joely Kaufman-Janette, MD, a board certified dermatologist at Skin Associates of South Florida, and a CCH clinical trial investigator. "Many of my patients have expressed that they are self-conscious about their cellulite and looking for something to effectively treat it. The fact that CCH is a potential new injectable option to treat cellulite will be very meaningful for my patients and for the aesthetics industry overall."

Primary Endpoint for RELEASE-1:

• 7.6 percent of subjects receiving CCH demonstrated a highly significant (p=0.006) improvement in the composite investigators' and patients' assessments of the appearance of cellulite, as measured by a two-level response in both the Clinician Reported- Photonumeric Cellulite Severity Scale (CR-PCSS) and Patient Reported- Photonumeric Cellulite Severity Scale (PR-PCSS) scores, for the target buttock at Day 71, compared to only 1.9 percent of placebo subjects.

Primary Endpoint for RELEASE-2:

• 5.6 percent of subjects receiving CCH demonstrated a highly significant (0.002) improvement in the composite investigators' and patients' assessments of the appearance of cellulite, as measured by a two-level response in both the CR-PCSS and PR-PCSS scores, for the target buttock at Day 71, compared to only 0.5 percent of placebo subjects.

Key Secondary Endpoints for both RELEASE-1 and RELEASE-2:

• 37.1 percent of subjects in RELEASE-1, and 41.6 percent of subjects in RELEASE-2 receiving CCH demonstrated a highly significant 1-level response in the composite investigators' and patients' assessments of the appearance of cellulite, as measured by both the CR-PCSS and PR-PCSS scores, for the target buttock at Day 71, compared to only 17.8 percent and 11.2 percent of placebo subjects respectively.
• 24.3 percent of subjects in RELEASE-1, and 21.0 percent of subjects in RELEASE-2 receiving CCH demonstrated a highly statistically significant 2-level improvement on the patients' assessment of the appearance of cellulite in the target buttock at Day 71, as measured by the PR-PCSS scores compared to only 12.2 percent and 5.8 percent of placebo subjects respectively.
• 54.3 percent of subjects in RELEASE-1, and 57.9 percent of subjects in RELEASE-2 receiving CCH demonstrated a highly statistically significant 1-level improvement on the patients' assessment of the appearance of cellulite in the target buttock at Day 71, as measured by the PR-PCSS scores compared to only 36.2 percent and 29.6 percent of placebo subjects respectively.
• 48.6 percent of subjects in RELEASE-1, and 42.1 percent of subjects in RELEASE-2 receiving CCH demonstrated a highly statistically significant 1-level improvement on the patients' assessment of the appearance of cellulite in the target buttock at Day 71, as measured by the SSRS (Subject Self Rating Scale) compared to only 22.5 percent and 15.0 percent of placebo subjects respectively.
• 54.3 percent of subjects in RELEASE-1, and 46.8 percent of subjects in RELEASE-2 receiving CCH reported being "Satisfied" or "Very Satisfied" with their cellulite treatment as assessed by the Subject Satisfaction with Cellulite Treatment Assessment at Day 71, compared to only 25.8 percent and 13.6 percent of placebo subjects respectively.
• 73.3 percent of subjects in RELEASE-1, and 67.8 percent of subjects in RELEASE-2 receiving CCH were reported as "Improved" or "Very Improved" or "Very Much Improved" in global appearance of their cellulite area as assessed by the Subject- Global Aesthetic Improvement Scale in the target buttock at Day 71, compared to only 43.2 percent and 24.1 percent of placebo subjects respectively.
• Subjects receiving CCH demonstrated a statistically significant improvement in the composite investigators' and patients' assessments of the appearance of cellulite, as measured by a 2-level improvement in both the CR-PCSS and PR-PCSS scores, for the non-target buttock at Day 71 for RELEASE-1 study but failed to show statistical significance in RELEASE-2 study.

Consistent with earlier studies of CCH for the treatment of cellulite, CCH was well-tolerated in the Phase 3 studies by all dose groups with most adverse events (AEs) being mild to moderate and primarily limited to the local injection area. The most common AEs in the trial were injection site bruising, injection site pain, injection site discoloration, injection site nodule and injection site pruritus.