Auxilium Pharmaceuticals, Inc., a specialty biopharmaceutical company, has reported top-line Day 30 data for collagenase clostridium histolyticum or CCH for the potential treatment, if approved by the US Food and Drug Administration (FDA), of adult patients with edematous fibrosclerotic panniculopathy (EFP), commonly known as cellulite.  

The phase Ib study is a single site, open-label dose-escalation study that enrolled 99 women between 21 and 60 years of age. Study participants were assigned to one of 11 arms, each of which varied in treatment dose, injection concentration and volume, to receive a single injection of CCH, divided into 10 aliquots over a pre-defined 8x10cm template around a target dimple.  

The objectives of the study are to assess the safety and effectiveness of a single injection of CCH for the treatment of EFP at 30, 60 and 90 days across multiple dosing arms.  Pharmacokinetic evaluations were made as well.  

Across all dosing arms, 60 patients (63%) who were treated experienced some improvement in the volume of their target cellulite dimple at Day 30.  Overall, 17% of patients had a greater than or equal to 30% improvement in their target dimple at Day 30; however, multiple CCH dosing arms had more than 40 per cent of patients experience an improvement greater than or equal to 30% in their target dimple at Day 30.  Cellulite has been reported to occur in 85-98% of post-pubertal females and rarely in men; the condition is believed to be prevalent in women of all races.

"We are pleased with the safety profile and encouraging potential efficacy of CCH, with initial phase Ib results demonstrating that some doses of CCH exhibited potential improvement in dimple volume and were well tolerated with no dose-limiting side effects," said Dr. James Tursi, chief medical officer at Auxilium. "We look forward to advancing the clinical development of CCH in cellulite, which, if successful, we believe could lead to the first FDA-approved, office-based biological treatment option for cellulite that is supported by scientific results."

Treatment-related adverse events with CCH were mostly localized bruising, injection site discomfort and swelling, and all such events resolved without intervention, which are all consistent with Xiaflex use in other indications.  There were no new adverse events and no drug-related serious adverse events reported.

The following 3-D images represent baseline and Day 30 images of target dimples from two subjects who participated in the study.  Red colour identifies the deepest areas within the target dimple, while blue colour shows the areas with shallower depth closest to the normal skin surface.  Following a single injection of Xiaflex , subject 1227 demonstrated a 30.6% improvement in target dimple volume at Day 30 and subject 1057 demonstrated a 42.1% improvement in target dimple volume at Day 30.  These results are not representative of all subjects, but help demonstrate the extent of visible improvement across patients.

"Thirty-day data from our phase Ib cellulite clinical trial represents another important development milestone for Auxilium as we advance a fourth potential indication of CCH in development, further diversifying Xiaflex's growing pipeline," explained Adrian Adams, chief executive officer and president of Auxilium. "We believe cellulite represents a significantly undertreated condition and that innovative approaches such as CCH may, if approved, one day be a viable solution for treatment."

Cellulite, also known medically as edematous fibrosclerotic panniculopathy or EFP, describes a pathologic condition, in which lobules of subcutaneous adipose tissue extend into the dermal layer.  Cellulite can involve the loss of elasticity or shrinking of collagen cords, called septae, that attach the skin to lower layers of muscle. When fat in cellulite prone areas swells and expands, the septae tether the skin, which causes surface dimpling characteristic of cellulite.  These changes can visibly affect the shape of the epidermis and resemble an orange peel-like dimpling of the skin.    CCH treatment 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.

Xiaflex (collagenase clostridium histolyticum or CCH) is a biologic approved in the US, EU and Canada for the treatment of adult Dupuytren's contracture patients with a palpable cord. Xiaflex is a minimally invasive treatment for this condition and consists of a highly purified combination of subtypes of collagenase, derived from Clostridium histolyticum, in a specific proportion. Together, the collagenase sub-types work synergistically to break the bonds of the triple helix collagen structure more effectively than human collagenase. Xiaflex is currently under review by the FDA for the treatment of Peyronie's disease.  CCH is also in phase IIa of development for the treatment of Frozen Shoulder syndrome (adhesive capsulitis) and in phase Ib of development for the treatment of cellulite (edematous fibrosclerotic panniculopathy).