Clinical data

DUROLANE is a stabilised hyaluronic acid (HA), from a non-animal source, therapy for the intra-articular treatment of mild to moderate osteoarthritis in hip and knee joints.²

DUROLANE uses advanced and unique NASHA (non-animal hyaluronic acid) technology which gives it a unique gel bead structure. The patented stabilisation technique ensures that the naturally cross-linked and entangled HA network is kept in place by introducing a very limited number of synthetic cross-links, resulting in minimal modification.⁸

A history of safe use*

DUROLANE does not generate product specific antibodies²⁰

Mice were injected with different HA products under the skin in an air pouch. Then blood samples were obtained to test for antibody production.

Antibody levels in DUROLANE treated animal blood were no different compared to controls
DUROLANE did not cause a systemic immune response
Antibody levels in Hylan G-F 20 treated animal’s blood were significantly greater than saline or DUROLANE
Hylan G-F 20 stimulated a systemic immune response

* Over 1 million injections with low post marketing adverse event rate.

DUROLANE-history-of-safe-use — Antibody Binding to Viscosuplements,as seen with increased optical density. Mean ± SEM (Standard Error of the Mean)

Significant and sustained benefits for hip^21,22 and knee^12,13 OA patients

Effectiveness in comparison to corticosteroid¹³

A randomised, blinded trial comparing one hyaluronic acid (HA) injection to corticosteroid for knee osteoarthritis pain:

The pain relief effect measured in WOMAC pain responder rate* of DUROLANE was shown to be non-inferior to methylprednisolone over 12 weeks (442 patients, NASHA: 44.6%; MPA: 46.2%; difference [95% CI]: 1.6% [ – 11.2%; + 7.9%]).
Based on the improvement from baseline, DUROLANE has shown to be longer lasting than methylprednisolone steroid at 26 weeks post-single injection treatment (p=0.034).

^{* WOMAC pain responder rate: the percentage of patients with ≥40% improvement from baseline in WOMAC pain score and an absolute improvement of ≥5 points.}

Effectiveness in hips

Significant (p<0.05) improvements at six months following injection under fluoroscopic control²²:

Forty patients with hip OA were treated with a single intra-articular injection of DUROLANE.
Walking Pain, Patient Global Assessment, WOMAC A & B decreased significantly between baseline and six months (p<0.05).
71% were classified OMERACT-OARSI* responders.

^{* Pham T, Van Der Heijde D, Altman RD, Anderson JJ, Bellamy N, Hochberg M, et al. OMERACT-OARSI Initiative: Osteoarthritis Research Society International set of responder criteria for osteoarthritis clinical trials revisited. Osteoarthritis Cartilage. 2004; 12:389–399.}

Long lasting by design⁸

DUROLANE uses unique and advanced NASHA technology to increase residence time in the joint.^8,14,17

Data from human and animal studies have shown that:

DUROLANE has a half-life of 4 weeks or 32 days in the joint in a single injection treatment regimen.^14,17
DUROLANE has a longer half-life than unstabilized hyaluronic acid (HA) and cross-linked Synvisc^® (Hylan G-F 20).^15,16

Graphs based on elimination of hyaluronic acid (HA) from the joint space of rabbits as a function of time for DUROLANE¹⁷ as compared against extrapolated data for the residence time of Hylan G-F 20¹⁵and low molecular weight HA¹⁶ in a similar rabbit model. DUROLANE values calculated based on projected clearance of one-3ml injection (20mg/ml). Hylan G-F 20 values calculated based on projected clearance of one-6ml injection (representing Synvisc-One^®) or three-2.0ml injections (representing Synvisc-3 injection regimen) of HA at 16 mg/ml in a rabbit model.¹⁵ As shown in the graph, DUROLANE human data correlates well with the rabbit model.¹⁴*

*At this time there is no known evidence to indicate whether there is any correlation between the residency period of HA in a joint and the safety or efficacy of HA to treat a joint.
^{Synvisc-One and Synvisc are registered trademarks of Genzyme Corporation.}

Pre-clinical evidence for the efficacy of DUROLANE

DUROLANE prevented knee osteoarthritis (OA) progression in an animal model.³

In an OA model:

DUROLANE injection protected joints from femoral cartilage erosion as well as tibial and femoral tissue fibrosis.
DUROLANE maintained the gait pattern (stance time) to that observed prior to the experiment, whereas animals treated with saline had worsening gait pattern, as observed by increasing stance time.

Pre-clinical evidence for the efficacy of DUROLANE — Joint Tissue Pathology Scores showing the protective effects of prophylactic hyaluronan (HA) on murine joint osteoarthritis (OA). (a) Cartilage erosion scores and (b) fibrosis scores for the OA (n=8 ± standard deviation) and OA + DUROLANE (n=8 ± standard deviation) groups illustrate the statistically significant and area-specific effects of DUROLANE on murine OA pathology.

DUROLANE provided superior pain relief, compared to Synvisc^®, in an animal knee joint pain model⁴

DUROLANE was compared to other hyaluronic acid (HA) preparations* and a saline control:

The saline control was least effective at pain relief shown by the least amount of pressure applied to the knee joint after injection to induce a response.
The pain relief DUROLANE provided was significantly better than unmodified sodium hyaluronate and Hylan G-F 20 at multiple time points (* p<0.05: ** p<0.01).
A single injection of DUROLANE provided pain relief out to 56 days in this animal knee pain model.

DUROLANE-provided-superior-pain- relief — Mechanical threshold data (means ± SEM) for the affected limb. The mean force required to cause withdrawal for the morphine group was 246.3g.
BL = Baseline testing.

Primary mechanical pain threshold was assessed following an injection of pain inducing agents by ascending pressure applied to the animal knee joint, after a single injection of NASHA (50 μl, n = 11), Hylan G-F 20 (100 μl, n = 9), and sodium hyaluronate (33 μl, n = 11). Although saline-treated animals showed a dramatic drop in mechanical thresholds from day 1, all hyaluronic acid compounds showed antinociceptive properties. These were most pronounced for NASHA and Hylan G-F 20, which were superior to unmodified sodium hyaluronate, particularly in the later stages.
* Preparations used included: NASHA (DUROLANE), Hylan G-F 20 (Synvisc^®) and unmodified sodium hyaluronate (Hyalgan^®).

NOTE: Clinical dosage of Hyalgan^® is three or five injections. Model utilizes single injection.
Model Of Repetitive Joint Pain. Arthritis Research & Therapy 13.4 (2011): R110.

^{Synvisc-One and Synvisc are registered trademarks of Genzyme Corporation.}^{Hyalgan is a registered trademark of Fidia Farmaceutici S.p.A., Italy.}

Effective relief from osteoarthritis pain with one safe treatment^{9,11,13,21,22}

Effective relief from osteoarthritis pain with one safe
treatment^{9,11,13,21,22}

DUROLANE is a single-injection treatment to relieve the pain of osteoarthritis in joints of all sizes.¹ It is based upon a safe and proven technology of stabilized hyaluronic acid (HA), NASHA. HA is a naturally occurring molecule that provides the lubrication and cushioning in a normal joint.