Data supports efficacy of XIAPEX® (collagenase clostridium histolyticum)

Data presented for the first time at the annual congress of the Federation of European Societies for Surgery of the Hand (FESSH), further supports the role of XIAPEX® (collagenase clostridium histolyticum) as a minimally invasive option in the treatment of Dupuytren’s contracture in adult patients with a palpable cord.1,2 XIAPEX is the first injectable treatment approved in the EU for Dupuytren’s contracture after receiving marketing authorisation from the European Medicines Agency in February 2011 for the treatment of adult patients with a palpable cord.3

Dupuytren’s disease is a slowly progressive condition affecting the layer of connective tissue in the palm of the hand and the fingers, which affects 3 to 13% of the European population4-9. Dupuytren’s disease can progress into Dupuytren’s contracture, whereby the affected finger bends permanently toward the palm. Once contracture has occurred, the affected finger often affects the ability to carry out everyday tasks.

The studies presented today examined range of motion and degrees of contracture from two pivotal trials – a pooled analysis from the Collagenase Option for Reduction of Dupuytren’s trials (CORD I and II), and data from the subgroup of European patients enrolled in the Joint Open-label Injection Non-surgical Treatment II (JOINT II) trial.

Pooled analysis from CORD I and II

The results from CORD I and II unveiled today conclude that patients treated with XIAPEX (compared with those injected with placebo) experience a significant change in degrees of contracture and an improvement in range of motion, and provide further evidence that XIAPEX is an effective and generally well tolerated treatment option for Dupuytren’s contracture.

These results were pooled to provide an overall analysis of efficacy and safety of XIAPEX versus placebo for range of motion and contracture. 372 patients with a contracture in a metacarpophalangeal (MP) joint (20-100 degrees) or proximal interphalangeal (PIP) joint (20-80 degrees) were randomised to receive up to three singular injections of XIAPEX or placebo in the contracted cord at 30 day intervals. The primary endpoint was defined as the percentage of patients achieving a reduction in contracture to 5 degrees or less, approximately 30 days after the last injection.1

In the MP joints treated with XIAPEX, there was a mean increase in range of motion of 40.6±19.2 degrees (baseline range of motion 42.2±19.1 degrees), which was significantly different (P<0.0001) from the change in placebo-treated MP joints, where range of motion increased 4.4±13.0 degrees from baseline (45.1±19.4).1 For PIP joints treated with XIAPEX, range of motion increased 29.8±20.6 degrees from baseline (44.9±19.8); range of motion in placebo-treated PIP joints increased 5.1±17.8 degrees from baseline (45.0±16.4; P<0.0001).1

Efficacy and tolerability of Xiapex in European patients with Dupuytren’s contracture

Similar results, also being presented today, were observed in a subgroup of European patients enrolled in JOINT II, a 9-month open label study. In this trial, 137 European patients with primary flexion deformities of 20-100 degrees for MP joints or 20-80 degrees for PIP joints received up to a maximum of three injections at 30-day intervals.2 The primary endpoint was clinical success, defined as a reduction in contracture to 5 degrees or less, 30 days after the last injection.2 61.3% of MP and 37.9% of PIP joints met this primary endpoint.2 Range of motion in MP joints increased from 46.6±18.9 degrees at baseline to 82.4±16.3 degrees at day 30, and from 53.8±18.30 degrees to 80.9±17.9 degrees in PIP joints.2 Additionally, patient satisfaction and physician ratings of improvement after treatment with XIAPEX were significantly higher than with placebo treatment.2

Commenting on the results, Dr. Jörg Witthaut, consultant hand surgeon from Schön Klinik, Vogtareuth, Germany, and a co-investigator in the JOINT II trial said: “This data adds to the evidence base supporting the use of XIAPEX in the treatment of Dupuytren’s contracture as a non-surgical alternative in adult patients with a palpable cord. It is also encouraging to see that patients and physicians are satisfied with XIAPEX as a viable treatment option.

The studies also demonstrated that XIAPEX was generally well tolerated.1,2 In the pooled analysis of CORD I and CORD II, the majority of XIAPEX-treated patients experienced at least one treatment-related adverse event (AE), most of which were mild or moderate in intensity and resolved without intervention within two weeks.1 One serious treatment-related AE occurred in each of four patients. The European patients enrolled in JOINT II reported at least one treatment-emergent AE. The most commonly reported AEs were localised bruising, oedema, haemorrhage, pain, swelling, and tenderness and most resolved without intervention within a week.2 There were no serious AEs in JOINT II deemed to be related to treatment with XIAPEX.2

References

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2. Witthaut J, Milner R, Bainbridge C et al. Efficacy and tolerability of collagenase clostridium histolyticum in European patients with Dupuytren’s contracture: results from a multicenter, open-label study. Abstract presented at FESSH 2011
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