Durolane RPU 2010t

JOAcid injection for Osteoarthritis

VISKOSUPLEMEN INTRAARTIKULER PADA OSTEOARTRITIS

OSTEOARTHRITIS

• Most common joint disease in human

• Suffering of pain

• Causing disability in 2% of population in the world

Grading of knee OAKellgren-Lawrence

• Grade I

• Grade II

• Grade III

• Grade IV

Treatment of OA Non Pharmacological

- Patient education & empowerment

- Physiotherapy , occupational therapy & joint protection

Pharmacological

- Painkillers : Paracetamol, opioid, NSAIDs

- Intra-articular injection : corticosteroid, Hyaluronic acid (viscosupplementation)

Surgery

- Arthroscopy, osteotomy, Arthrodesis, joint replacement

ViscosupplementationEuropean League Against Rheumatism (EULAR)

• Recommends viscosupplementation for pain reduction and function improvement in the management of OA1

American College of Rheumatology (ACR)

• Recommends viscosupplementation for patients who have not responded to nonpharmacologic therapy or simple analgesics2

1. Jordan KM, Arden NK, Doherty M, et al. EULAR Recommendations 2003: an evidence based approach to the management of knee osteoarthritis: report of a task force of the Standing Committee for International Clinical Studies Including Therapeutic Trials (ESCISIT). Ann Rheum Dis. 2003;62:1145-1155. 2. American College of Rheumatology Subcommittee on Osteoarthritis Guidelines. Recommendation for the medical management of osteoarthritis of the hip and knee. Arthritis Rheum. 2000;43:1905-1915.

Viscosupplementations

1. Rooster combs hyaluronic acid (Hyalgan®)

2. Synthetic cross-linked hyaluronic acid

(Synvisc®)

3. Bacterial fermentation (Nuflexa®)

4. NASHATM / Non Animal Stabilized

Hyaluronic Acid (Durolane®)

Hyaluronic Acid Glycosaminoglycan

Poly d-glucuronic acid-n-acetyl-d-glucosamine

Hyaluronate

Synthesis of Hyaluronic Acid

Enzyme : Hyaluronic Acid Synthase

Mechanism of action of Viscosupplementation

1. Restoration of the elastoviscous properties

of synovial fluid

2. Anti-inflamatory & antinociceptive

properties

Greatest advantages with

HA

* Datamonitor 2002 (interviews)

• Ability to delay surgery

• Treatment given as an out-patient setting

• No drug medication (no regime of medicine)

• It works among majority of patients

• HA reduces NSAID´s consumptions

Greatest disadvantages

with HA

* Datamonitor 2002 (interviews)

• Number of injections

• Risk involved with several injections

NASHA Technology

• Combination of modern biotechnological techniques &

carefully controlled stabilisation process

NASHA Technology

• Non-Animal

−Produced by bacterial fermentation.

−Elimination of:

• animal-related allergic reaction.

• risk of transfer of diseases from animals.

• Stabilized:

−Long duration → single injection treatment.

−Minimal tissue disturbance.

• Patent protection until 2015.

NASHA Technology High purity

Mildest form of stabilisation : binds to receptors as effectively as

unmodified HA

Low degree of molecular cross-linking (<0.5% -1%) ensures

biocompatibility is retained (assured safety profile)

Highest molecular weight (1013)

Prolonged half life (4 weeks) (Note : t½ Hyalgan = 13.2 hours, t½

Synvisc = 1.5-8.8 days)

Permits very high density of HA (high dose)

Superior viscoelasticity (superior cushioning of joint) compared to all

comparators

NASHA Technology

Mildest form of stabilisation

NASHA Technology – 3-dimension

NASHA product consist of three-dimensional network of hyaluronic acid

NASHA Synthetic HANatural HA

The Durolane® differences

The elastic modulus and viscous modulus as functions of frequency on log scales for Durolane®, Synvisc®, and Artzal®, in comparison with endogenous HA from a young healthy subject, an old healthy subject, and a patient with osteoarthritis.14

14. Ågerup B, Berg P, Åkermark C. Non-animal stabilised hyaluronic acid: a new formulation for the treatment of osteoarthritis. BioDrugs. In press.

Bohlin VOR Rheometer System

Content

• 3 ml prefilled glass syringe

• Each ml contains

- Stabilized hyaluronic acid 20 mg

- Phys. NaCl solution, pH 7 qs.

Indications

Symptomatic treatment of mild to moderate knee or hip osteoarthritis

Contraindications

None known

Dosage & Administration

Single dose 3 ml (one syringe) per knee or hip joints Recommended needle size : 18 – 22 G

The single-injection advantage

Overall intra-articular exposure to HA following i²€tion of different HA preparations. Synvisc is a registered trademark of Genzyme Corporation. Artzal is a registered trademark of Seikagaku Corporation.

Elimination comparison of Durolane®, Synvisc®, and Artzal®4-7

4. Synvisc® (Hylan GF 20) Prescribing Information, Genzyme Corp., Cambridge, MA. Available at: www.synvisc.com. Accessed February 15, 2005. 5. Brown TJ, Laurent UN, Frazer JR. Turnover of hyaluronan in synovial joints: elimination of labeled hyaluronan from the knee joint of the rabbit. Exp Physiol. 1991;76:125-134. 6. Lindenhayn K, Heilmann HH, Niederhausen T, et al. Elimination of tritium-labelled hyaluronic acid from normal and osteoarthritic rabbit knee joints. Eur J Clin Chem Clin Biochem. 1997;35:355-363. 7. Lindqvist U, Tolmachev V, Kairemo K, Åström G, Jonsson E, Lundqvist H. Elimination of stabilised hyaluronan from the knee joint in healthy men. Clin Pharmacokinet. 2002;41:603-613.

Warnings

Durolane should not be injected :If the joints is infected or severely inflammed

If there is an active skin disease or infection

present at or near the injection site

Intravascularly or extra-articularly or in the

synovial tissues or capsule

Adverse events

Transient pain

Swelling

Stiffness

In OA of the knee:restoring flexibility

Åkermark C, Adalberth T, Ericsäter J, Isacsson J. Patient-perceived efficacy of non-animal stabilized hyaluronic acid in the treatment of osteoarthritis of the knee. Poster presented at OARSI 2004.

In OA of the knee:an advantage for patientsPatients responding after a

single injection of Durolane®13Patient response after a

single injection of Durolane®15

13. Åkermark C, Berg P, Björkman A, Malm P. Non-animal stabilized hyaluronic acid in the treatment of osteoarthritis of the knee—a tolerability study. Clin Drug Invest. 2002;22:157-166. 15. Altman RD, Moskowitz RW, Group atHS. Intra-articular hyaluronate (Hyalgan) in the treatment of patients with osteoarthritis of the knee: a randomized clinical trial. J Rheumatol. 1998;25:2203-2212.

In OA of the knee:

NASHA

Placebo

** P < 0.05

Percent response rate (WOMAC pain score)

Altman RD, Akermark C, Beaulieu,etal. Effficacy and safety of a single intraarticular injection of non-animal stabilized hyaluronic acid (NASHA) in patientsWith osteoarthritis of the knee. Osteoarthritis Cartilage 2004; 12:624-9

WOMAC = Western Ontario and McMaster Universities Osteoarthritis Index

In OA of the hip:the new flexible advantage

Improvement in WOMAC scores8

Patient assessment of global status8

8. Berg P, Olsson U. Intra-articular injection of non-animal stabilised hyaluronic acid (NASHA) for osteoarthritis of the hip: a pilot study. Clin Exp Rheumatol. 2004;22:300-306.

One flexible advantage Restores mobility and flexibility to the knee and hip

with the convenience of a single injection Cushions the blow of OA with proven pain relief and patient

satisfaction Superior physiochemical properties compared to

other HA preparations Well tolerated and safe

− Longer half life : one injection / 6 months− Non animal origin (↓ allergic reaction, ↓ risk of transfer of diseases from

Animal )

NASHATM

-based products have benefited patients throughout the world in numerous indications

Durolane is a registered trademark and NASHA is a trademark owned by Q-Med AB.

All content © 2005, Q-Med AB.