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Auxilium Pharmaceuticals, Inc. Announces XIAFLEX(TM) Meets Primary Endpoint With Statistical Significance (p < 0.001) in CORD I Pivotal Phase III Study for Dupuytren's Contracture
MALVERN, PA, USA | Jun 03, 2008 | Auxilium Pharmaceuticals, Inc. Announces XIAFLEX(TM) Meets Primary Endpoint With Statistical Significance (p < 0.001) in CORD I Pivotal Phase III Study for Dupuytren's Contracture
XIAFLEX Also Meets Primary Endpoint (p < 0.001) in Australian CORD II Phase III Study; Pharmacokinetic Study Demonstrates Lack of Systemic Exposure of XIAFLEX; Serious Adverse Events Occurring at a 0.33% Rate per XIAFLEX Injection; Conference Call Scheduled for Today, June 3, at 8:45 a.m. Eastern Time
MALVERN, PA--(June 03, 2008) - Auxilium Pharmaceuticals, Inc. (NASDAQ: AUXL) today announced positive top-line efficacy and safety results from the CORD I and CORD II phase III clinical trials for XIAFLEX(TM) (clostridial collagenase for injection) in the treatment of Dupuytren's contracture. Each of the CORD I and II trials successfully met the primary endpoint, a reduction in the angle of a patient's joint contracture to less than or equal to 5 degrees of normal, as measured by digital goniometry, 30 days after the last injection. The Company also released results of a Pharmacokinetic ("PK") Study that demonstrate the lack of systemic exposure of XIAFLEX in patients treated for Dupuytren's contracture. The most common adverse events in the CORD I and II and PK studies were consistent with adverse events reported in previous trials and included pain, swelling, bruising and pruritis at the injection site and transient lymph node swelling and pain. In over 2,000 XIAFLEX injections administered in approximately 850 patients through the end of May 2008, a total of seven serious adverse events ("SAEs") possibly related to study drug have been reported, five of which are related to tendon or ligament injury (rate per injection = 0.24%).
"We believe that this is a great day for the patients who suffer from Dupuytren's contracture, the physicians who treat the disease, and Auxilium, as XIAFLEX appears to offer a safe and effective, non-surgical treatment for Dupuytren's contracture," said Armando Anido, Auxilium's Chief Executive Officer and President. "We expect the results of these trials, together with all previous clinical and pre-clinical data, will enable us to submit a Biologics License Application for XIAFLEX in Dupuytren's contracture in early 2009. I wish to thank all the patients, investigators and Auxilium employees who contributed to these trials."
CORD I Efficacy Results
CORD I is the largest placebo-controlled study ever conducted in Dupuytren's contracture patients and the second U.S. pivotal phase III study for XIAFLEX in Dupuytren's contracture. A total of 306 patients evaluable for efficacy enrolled in 16 clinical sites across the U.S., with 203 patients receiving XIAFLEX and 103 receiving placebo in the double-blind portion of the study. The joints were stratified 2:1 Metacarpal Phalangeal Joint, or MP joint, to Proximal Intra-Phalangeal, or PIP joint. The primary endpoint was met with 64% (130 of 203) of patients' primary joints treated with XIAFLEX achieving less than or equal to 5 degrees of normal contracture, compared to only 6.8% (7 of 103) of patients' primary joints treated with placebo (p < 0.001). On average, Dupuytren's contracture patients who achieved the primary endpoint received 1.5 XIAFLEX injections.
In addition to the primary endpoint, there were 26 secondary endpoints that were measured, each of which was met with statistical significance. The Company believes two important secondary endpoints are the difference between the pre- and post-treatment contracture angles and whether patients achieved at least a 50% reduction in their contracture compared to baseline. First, the average percent improvement in contracture from baseline was 79.3% (50.2 degrees average contracture at baseline down to 12.2 degrees average contracture after treatment) for primary joints treated with XIAFLEX, compared to placebo patients, where the average percent improvement in contracture from baseline was 8.6% (49.1 degrees average contracture at baseline down to 45.7 degrees average contracture after placebo treatment) (p < 0.001). Second, 84.7% of patients (172 of 203) treated with XIAFLEX achieved at least a 50% reduction in their primary joint contracture from baseline, compared with 11.7% of patients (12 of 103) treated with placebo (p < 0.001).
Dr. Lawrence Hurst, M.D., Professor and Chair, Department of Hand Surgery, Department of Orthopaedics of the Health Science Center, State University of New York at Stony Brook, an investigator in the CORD I clinical trial, said, "I believe these clinical results are very encouraging for patients with Dupuytren's contracture. As a surgeon, I am pleased to get contracture improvement to less than or equal to 5 degrees of normal in 50-60% of patients who undergo surgery. Based on the risk/benefit profile demonstrated in the data released today, I would anticipate that XIAFLEX will offer a strong therapeutic alternative to surgery and could potentially become the new first-line treatment option for Dupuytren's contracture."
CORD II Efficacy Results
CORD II enrolled a total of 66 Dupuytren's contracture patients in five clinical sites across Australia. Forty-five patients received XIAFLEX and 21 received placebo in the double-blind portion of the study. The joints were stratified 1:1 MP to PIP. The primary endpoint was met, with 44.4% (20 of 45) of patients' primary joints treated with XIAFLEX achieving less than or equal to 5 degrees of normal contracture, compared to only 4.8% (1 of 21) of patients' primary joints treated with placebo (p < 0.001). On average, Dupuytren's contracture patients who achieved the primary endpoint received 1.5 XIAFLEX injections.
Within the CORD II study, average percent improvement in contracture from baseline was 70.5% (53.2 degrees average contracture at baseline down to 16.7 degrees average contracture after treatment) for primary joints treated with XIAFLEX. For placebo patients, the average percent improvement in primary joint contracture from baseline was 13.6% (50 degrees average contracture at baseline down to an average 44.3 degrees after placebo treatment) (p < 0.001). A greater than or equal to 50% reduction from baseline in the affected joint's contracture was achieved in 77.8% of patients (35 of 45) of all primary joints treated with XIAFLEX compared to 14.3% of patients (3 of 21) for joints treated with placebo (p < 0.001).
"As described in the available literature on surgery and as we have seen in previous XIAFLEX clinical studies, the CORD I and II trials demonstrate that MP joints generally respond better to treatment than PIP joints, and joints of lesser severity generally respond better than joints of higher severity," said Dr. Tony DelConte, Chief Medical Officer for Auxilium. "We believe these findings will be well-received by the physician and patient community who have expressed a desire to treat affected joints earlier than current surgical practice."
Pharmacokinetic Study Results
An open label study was conducted to assess the pharmacokinetics of a single injection of XIAFLEX in 16 subjects with Dupuytren's contracture. Nine patients with MP contractures and seven patients with PIP contractures were enrolled in the study. No measurable levels of XIAFLEX were detected in plasma from 5 minutes to 30 days post injection.
Although the study was not designed to measure efficacy in comparison to placebo, 12 of the 16 patients achieved less than or equal to 5 degrees of normal contracture after their only injection of XIAFLEX.
Adverse Events
The most common adverse events reported in the CORD I and II and PK studies were pain, swelling, bruising and pruritis at the injection site and transient lymph node swelling and pain. These adverse events were consistent with previous trials. No systemic allergic reactions were noted.
In data from the CORD I and II studies, the open label JOINT I and II studies and the PK study, over 2,000 XIAFLEX injections have been administered to approximately 850 patients through the end of May 2008. There have been seven SAEs possibly related to drug (rate per injection = 0.33%). There have been a total of three confirmed tendon ruptures (rate per injection = 0.14%), one reported tendon rupture remains unconfirmed (rate per injection = 0.05%), and one pulley ligament injury (rate per injection = 0.05%). Additionally, one complex regional pain syndrome (rate per injection = 0.05%) and one deep vein thrombosis ("DVT") (rate per injection = 0.05%) occurred. Three SAEs occurred in CORD I (two tendon ruptures and the complex regional pain syndrome), two occurred in JOINT II (DVT and a tendon rupture), one occurred in CORD II (a pulley ligament injury) and one tendon rupture occurred in the PK study.
"In summary, we believe that based on all clinical data for XIAFLEX in Dupuytren's contracture to date, we are positioned to bring a novel therapeutic to market that has the potential to revolutionize the treatment of Dupuytren's contracture," stated Mr. Anido. "The data indicate that approximately 4 out of 5 patients may achieve at least a 50% reduction in their contractures, and we believe the rate of reported serious adverse events compares favorably to the complications of surgery described in the available literature."
Conference Call
Auxilium will hold a conference call today, June 3, 2008 at 8:45 a.m. ET, to discuss the results of the CORD I and II studies and the PK study and provide updates on the XIAFLEX programs in general. The conference call will be simultaneously web cast on Auxilium's web site and archived for future review until July 3, 2008. Reference materials for the conference call also will be available on Auxilium's web site.
About Dupuytren's Contracture
Dupuytren's contracture is a condition that affects the connective tissue that lies beneath the skin in the palm. The disease is progressive in nature. Typically, painful nodules develop in the palm as collagen deposits accumulate. As the disease progresses, the collagen deposits form a cord that stretches from the palm of the hand to the base of the finger. Once this cord develops, the patient's fingers contract and the function of the hand is impaired. Currently, surgery is the only effective treatment. The incidence of Dupuytren's contracture is highest in Caucasians, historically those of Northern European descent, with a global prevalence of three to six percent of the Caucasian population. (1) Most cases of Dupuytren's contracture occur in patients older than 50 years. (2)
The most frequently affected parts of the hand associated with Dupuytren's contracture are the joints called the Metacarpal Phalangeal Joint, or MP joint, which is the joint closest to the palm of the hand and the Proximal Intra-Phalangeal Joint, or the PIP joint, which is the middle joint in the finger. The little finger and ring finger are most frequently involved. There are currently no drugs approved by the U.S. Food and Drug Administration for Dupuytren's contracture, which is treated primarily by an open surgical procedure.
(1) American Academy of Orthopaedic Surgeons. http://orthoinfo.aaos.org/topic.cfm?topic=A00008
(2) Badalamente, M. A., Hurst, L. C. et al., Collagen as a Clinical Target: Nonoperative Treatment of Dupuytren's Disease, The Journal of Hand Surgery, (2002;27A:788-798)
About CORD I
The U.S. pivotal trial is a double-blind, randomized, placebo-controlled study of XIAFLEX with 308 patients enrolled in 16 sites throughout the U.S. The primary endpoint of the study is to determine if XIAFLEX can reduce the contracture angle in metacarpophalangeal (MP) or proximal interphalangeal (PIP) joints to less than or equal to 5 degrees of normal. In CORD I, MP and PIP patients were stratified in a 2:1 ratio.
All patients receiving XIAFLEX in the double-blind portion of the study will be monitored for a minimum of 12 months following initial dosing. After finishing the double-blind portion, XIAFLEX and placebo patients are also eligible to receive additional XIAFLEX injections for either unsuccessfully treated joints or additional untreated joints during an open-label, extended treatment period. This open-label phase was designed to provide further data for the long-term safety and efficacy of XIAFLEX injections in the treatment of Dupuytren's contracture.
About CORD II
This Australian study is a supportive double-blind, randomized, placebo-controlled study with an open-label extension that enrolled 66 patients in five sites. The design of this study is similar to that of the pivotal U.S. phase III trial (CORD I) and its open-label extension. The primary endpoint was the reduction of contracture angle in MP or PIP joints to less than or equal to 5 degrees of normal. In CORD II, MP and PIP patients were stratified in a 1:1 ratio.
After finishing this double-blind portion, patients from both XIAFLEX and placebo groups will be permitted to receive additional XIAFLEX injections for either unsuccessfully treated joints or additional untreated joints during an open-label, extended treatment period. This open-label phase was designed to provide further data for the long-term safety and efficacy of XIAFLEX injections in the treatment of Dupuytren's contracture.
About JOINT I and II
In addition to the open-label extensions of CORD I and II, the Company is concurrently conducting two phase III open-label studies in approximately 600 patients. These studies will provide additional safety and efficacy data and will contribute to the safety database that is required for the BLA.
About Auxilium
Auxilium Pharmaceuticals, Inc. is a specialty biopharmaceutical company with a focus on developing and marketing to urologists, endocrinologists, orthopedists and select primary care physicians. Auxilium markets Testim(R) 1%, a topical testosterone gel, for the treatment of hypogonadism through its approximately 190-person sales and marketing team. Auxilium has four projects in clinical development. XIAFLEX(TM) (clostridial collagenase for injection) is in phase III of development for the treatment of Dupuytren's contracture and is in phase II of development for the treatment of Peyronie's disease and Frozen Shoulder syndrome (Adhesive Capsulitis). Auxilium also has options to all indications using XIAFLEX for non-topical formulations. Auxilium's transmucosal film product candidate for the treatment of overactive bladder is in phase I of development. Auxilium has one pain product using its transmucosal film delivery system in pre-clinical development and has rights to seven additional pain products and products for hormone replacement and urologic disease using its transmucosal film delivery system. For additional information, visit http://www.auxilium.com.
SOURCE: Auxilium Pharmaceuticals, Inc. |
