Highly Statistically Significant Results (P<0.001) Demonstrated on Primary Composite Endpoint and All Secondary Endpoints
DUBLIN, Ireland I November 17, 2016 I Endo International plc (NASDAQ / TSX: ENDP) announced today positive results from its Phase 2b study of collagenase clostridium histolyticum (or “CCH”) for the treatment of edematous fibrosclerotic panniculopathy (“EFP”), commonly known as cellulite. CCH is known in its currently approved indications in the U.S. as XIAFLEX® for adult Dupuytren’s contracture and Peyronie’s disease. Trial subjects receiving CCH showed statistically significant levels of improvement in the appearance of cellulite with treatment, as measured by the trial’s primary endpoint (p<0.001), compared to those subjects receiving placebo. 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.
Pre- and post-treatment photos of placebo-treated subject
“We continue to be encouraged and very excited by the promising results of our CCH program, especially in the cellulite indication – a condition which affects many millions of people,” said Dr. Susan Hall, Executive Vice President, Chief Scientific Officer and Global Head of R&D at Endo. “We believe these data further reinforce our belief that CCH could be a potential treatment option for those with cellulite and we look forward to working with FDA to efficiently and effectively advance our development of the program into Phase 3.”
The Phase 2b trial enrolled 375 women with moderate or severe cellulite aged 18 years or older in the United States. Each subject received up to three treatment sessions of CCH (0.84 mg / session) or placebo with each treatment session occurring approximately 21 days apart. Twelve injections were administered into cellulite dimples during each session across an entire treatment quadrant – left or right buttock or left or right posteriolateral thigh. At both the outset and conclusion of the study period (28 days after the last treatment), cellulite severity was assessed by each patient and clinician using two photonumeric cellulite severity scales developed by Endo and third-party experts. The scales – the Photonumeric Cellulite Severity Scale (PCSS) – are 5-point scales ranging from 0 (no cellulite) to 4 (severe cellulite) that measure improvement in the appearance of cellulite.
The Phase 2b trial’s primary endpoint was the proportion of composite responders at Day 71 defined as subjects with a 2-point improvement in severity from baseline in the clinician-reported (CR) PCSS and a 2-point improvement in the patient-reported (PR) PCSS. Additional endpoints include a composite of 1-point responders, the percentage of responders with 1-point and 2-point improvements on the CR-PCSS and PR-PCSS, assessment of improvement by patient and clinician using the Global Aesthetic Improvement Scale (GAIS); subject satisfaction, and change in the Hexsel cellulite severity scale.
“I believe these positive results demonstrate that CCH has the potential to be a treatment option for cellulite, a condition for which there are very limited safe and proven effective treatments,” said Mitchel P. Goldman, MD, Medical Director, Cosmetic Laser Dermatology. “With so many millions of women affected by cellulite, there is a substantial need for new and innovative therapeutic options.”
Key Phase 2b Trial Results Include:
- Subjects receiving CCH demonstrated a highly statistically significant improvement in the primary endpoint of composite investigators’ and patients’ assessments of the appearance of cellulite, as measured by a two-point improvement in both the CR-PCSS and PR-PCSS scores, with a p-value of <0.001 versus placebo
- Subjects receiving CCH demonstrated a highly statistically significant improvement in the composite investigators’ and patients’ assessments of the appearance of cellulite, as measured by a one-point improvement in both the CR-PCSS and PR-PCSS scores, with a p-value of <0.001 versus placebo
- A highly significant proportion of CCH subjects reported being “Satisfied” or “Very Satisfied” with their cellulite treatment, compared to placebo subjects, with a p-value of <0.001
- A highly significant proportion of CCH subjects were reported as “Improved” or “Very Improved” or “Very Much Improved” in global appearance of their cellulite area as assessed by the subjects and investigators, compared to placebo subjects, with a p-value of <0.001
- CCH was well-tolerated by all dose groups with most adverse events (AEs) being mild to moderate and primarily limited to the local injection area; 92 percent of all related AEs were mild to moderate in the CCH group compared to 96 percent in the placebo group; the most common AEs were expected and included injection site bruising (approximately 75 percent) and injection site pain (approximately 59 percent)
“These data are exciting for the medical community and definitely warrant further investigation and development,” said Neil Sadick, MD, Clinical Professor of Dermatology, Weill Cornell Medical College. “By successfully advancing this program, we could offer patients currently seeking cellulite treatment a new and promising option.”
Results for an earlier Phase 2a trial of CCH for the treatment of cellulite demonstrated that three doses of CCH (low (0.06mg), mid (0.48mg) and high (0.84mg)) showed an improvement in the appearance of cellulite as measured by the trial endpoints of an investigator and a patient score on the GAIS, which was adapted for use in cellulite. The mid and high dose groups demonstrated a statistically significant improvement in the appearance of cellulite, as measured by GAIS scores, with a p-value of <0.05 compared to placebo for both endpoints. In the mid and high dose groups, 68 percent of patients reported being “Satisfied” or “Very Satisfied” with the results of their treatment, compared to only 34 percent of patients randomized to placebo. CCH was well-tolerated by all dose groups with most adverse events (AEs) being mild to moderate and primarily limited to the local injection area.
About Cellulite
Cellulite is a localized metabolic disorder of tissue under the skin that has been reported in 85 to 98 percent of post-pubertal females and affects women of all races and ethnicities[i] [ii]. The condition can involve the loss of elasticity or shrinking of collagen cords, called “septae,” that attach the skin to the muscle layers below. When fat in cellulite prone areas swells and expands, the septae tether the skin, which causes the surface dimpling characteristic of cellulite[iii]. CCH is intended to target and lyse, or break, those collagen tethers with the goal of releasing the skin dimpling and potentially resulting in smoothing of the skin. Despite multiple therapeutic approaches for the attempted treatment of cellulite, there are no FDA-approved pharmacological treatments and little scientific evidence that any current treatments are beneficial[iv].
About XIAFLEX
XIAFLEX® (collagenase clostridium histolyticum, or CCH) is a biologic approved in the U.S., EU, Canada, Australia and Japan for the treatment of adult Dupuytren’s contracture (DC) patients with a palpable cord and in the U.S. and EU for the treatment of adult men with Peyronie’s disease (PD) with a palpable plaque and penile curvature deformity of at least 30 degrees at the start of therapy. XIAFLEX® consists of a combination of two subtypes of collagenase, derived from Clostridium histolyticum. Together, the collagenase subtypes are thought to work synergistically to break the bonds of the collagen structure. XIAFLEX® has been granted Orphan status in the U.S. by the FDA for DC and PD.
About Endo International plc
Endo International plc (NASDAQ / TSX: ENDP) is a global specialty pharmaceutical company focused on improving patients’ lives while creating shareholder value. Endo develops, manufactures, markets and distributes quality branded and generic pharmaceutical products as well as over-the-counter medications though its operating companies. Endo has global headquarters in Dublin, Ireland, and U.S. headquarters in Malvern, PA. Learn more at www.endo.com.
SOURCE: Endo International
Post Views: 83
Highly Statistically Significant Results (P<0.001) Demonstrated on Primary Composite Endpoint and All Secondary Endpoints
DUBLIN, Ireland I November 17, 2016 I Endo International plc (NASDAQ / TSX: ENDP) announced today positive results from its Phase 2b study of collagenase clostridium histolyticum (or “CCH”) for the treatment of edematous fibrosclerotic panniculopathy (“EFP”), commonly known as cellulite. CCH is known in its currently approved indications in the U.S. as XIAFLEX® for adult Dupuytren’s contracture and Peyronie’s disease. Trial subjects receiving CCH showed statistically significant levels of improvement in the appearance of cellulite with treatment, as measured by the trial’s primary endpoint (p<0.001), compared to those subjects receiving placebo. 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.
Pre- and post-treatment photos of placebo-treated subject
“We continue to be encouraged and very excited by the promising results of our CCH program, especially in the cellulite indication – a condition which affects many millions of people,” said Dr. Susan Hall, Executive Vice President, Chief Scientific Officer and Global Head of R&D at Endo. “We believe these data further reinforce our belief that CCH could be a potential treatment option for those with cellulite and we look forward to working with FDA to efficiently and effectively advance our development of the program into Phase 3.”
The Phase 2b trial enrolled 375 women with moderate or severe cellulite aged 18 years or older in the United States. Each subject received up to three treatment sessions of CCH (0.84 mg / session) or placebo with each treatment session occurring approximately 21 days apart. Twelve injections were administered into cellulite dimples during each session across an entire treatment quadrant – left or right buttock or left or right posteriolateral thigh. At both the outset and conclusion of the study period (28 days after the last treatment), cellulite severity was assessed by each patient and clinician using two photonumeric cellulite severity scales developed by Endo and third-party experts. The scales – the Photonumeric Cellulite Severity Scale (PCSS) – are 5-point scales ranging from 0 (no cellulite) to 4 (severe cellulite) that measure improvement in the appearance of cellulite.
The Phase 2b trial’s primary endpoint was the proportion of composite responders at Day 71 defined as subjects with a 2-point improvement in severity from baseline in the clinician-reported (CR) PCSS and a 2-point improvement in the patient-reported (PR) PCSS. Additional endpoints include a composite of 1-point responders, the percentage of responders with 1-point and 2-point improvements on the CR-PCSS and PR-PCSS, assessment of improvement by patient and clinician using the Global Aesthetic Improvement Scale (GAIS); subject satisfaction, and change in the Hexsel cellulite severity scale.
“I believe these positive results demonstrate that CCH has the potential to be a treatment option for cellulite, a condition for which there are very limited safe and proven effective treatments,” said Mitchel P. Goldman, MD, Medical Director, Cosmetic Laser Dermatology. “With so many millions of women affected by cellulite, there is a substantial need for new and innovative therapeutic options.”
Key Phase 2b Trial Results Include:
- Subjects receiving CCH demonstrated a highly statistically significant improvement in the primary endpoint of composite investigators’ and patients’ assessments of the appearance of cellulite, as measured by a two-point improvement in both the CR-PCSS and PR-PCSS scores, with a p-value of <0.001 versus placebo
- Subjects receiving CCH demonstrated a highly statistically significant improvement in the composite investigators’ and patients’ assessments of the appearance of cellulite, as measured by a one-point improvement in both the CR-PCSS and PR-PCSS scores, with a p-value of <0.001 versus placebo
- A highly significant proportion of CCH subjects reported being “Satisfied” or “Very Satisfied” with their cellulite treatment, compared to placebo subjects, with a p-value of <0.001
- A highly significant proportion of CCH subjects were reported as “Improved” or “Very Improved” or “Very Much Improved” in global appearance of their cellulite area as assessed by the subjects and investigators, compared to placebo subjects, with a p-value of <0.001
- CCH was well-tolerated by all dose groups with most adverse events (AEs) being mild to moderate and primarily limited to the local injection area; 92 percent of all related AEs were mild to moderate in the CCH group compared to 96 percent in the placebo group; the most common AEs were expected and included injection site bruising (approximately 75 percent) and injection site pain (approximately 59 percent)
“These data are exciting for the medical community and definitely warrant further investigation and development,” said Neil Sadick, MD, Clinical Professor of Dermatology, Weill Cornell Medical College. “By successfully advancing this program, we could offer patients currently seeking cellulite treatment a new and promising option.”
Results for an earlier Phase 2a trial of CCH for the treatment of cellulite demonstrated that three doses of CCH (low (0.06mg), mid (0.48mg) and high (0.84mg)) showed an improvement in the appearance of cellulite as measured by the trial endpoints of an investigator and a patient score on the GAIS, which was adapted for use in cellulite. The mid and high dose groups demonstrated a statistically significant improvement in the appearance of cellulite, as measured by GAIS scores, with a p-value of <0.05 compared to placebo for both endpoints. In the mid and high dose groups, 68 percent of patients reported being “Satisfied” or “Very Satisfied” with the results of their treatment, compared to only 34 percent of patients randomized to placebo. CCH was well-tolerated by all dose groups with most adverse events (AEs) being mild to moderate and primarily limited to the local injection area.
About Cellulite
Cellulite is a localized metabolic disorder of tissue under the skin that has been reported in 85 to 98 percent of post-pubertal females and affects women of all races and ethnicities[i] [ii]. The condition can involve the loss of elasticity or shrinking of collagen cords, called “septae,” that attach the skin to the muscle layers below. When fat in cellulite prone areas swells and expands, the septae tether the skin, which causes the surface dimpling characteristic of cellulite[iii]. CCH is intended to target and lyse, or break, those collagen tethers with the goal of releasing the skin dimpling and potentially resulting in smoothing of the skin. Despite multiple therapeutic approaches for the attempted treatment of cellulite, there are no FDA-approved pharmacological treatments and little scientific evidence that any current treatments are beneficial[iv].
About XIAFLEX
XIAFLEX® (collagenase clostridium histolyticum, or CCH) is a biologic approved in the U.S., EU, Canada, Australia and Japan for the treatment of adult Dupuytren’s contracture (DC) patients with a palpable cord and in the U.S. and EU for the treatment of adult men with Peyronie’s disease (PD) with a palpable plaque and penile curvature deformity of at least 30 degrees at the start of therapy. XIAFLEX® consists of a combination of two subtypes of collagenase, derived from Clostridium histolyticum. Together, the collagenase subtypes are thought to work synergistically to break the bonds of the collagen structure. XIAFLEX® has been granted Orphan status in the U.S. by the FDA for DC and PD.
About Endo International plc
Endo International plc (NASDAQ / TSX: ENDP) is a global specialty pharmaceutical company focused on improving patients’ lives while creating shareholder value. Endo develops, manufactures, markets and distributes quality branded and generic pharmaceutical products as well as over-the-counter medications though its operating companies. Endo has global headquarters in Dublin, Ireland, and U.S. headquarters in Malvern, PA. Learn more at www.endo.com.
SOURCE: Endo International
Post Views: 83
