synolis va vs synvisc · synolis va powered by aptissen - - aptissen private & confidential 5...

SYNOLIS VA VS SYNVISC

SYNOLIS VA

3Synolis VA powered by Aptissen - - Aptissen Private & ConfidentialFOR INTERNAL USE ONLY

UNIQUE COMPOSITION

FIRST COMPANY TO ADD AN ANTIOXIDANT (SORBITOL) TO THE HA MOLECULE TO GET UNRIVALLED PROPERTIES OF THE GEL

CE MARK

STRONG SCIENCE BACKGROUND- PATENTED RHEOLOGICAL PROPERTIES / SYNOVIAL LIQUID (EU & USA PATENTS)- CLINICAL STUDIES

- SYNOLIS VA 40/80: CE MARK IN 2013- SYNOLIS VA 80/160: CE MARK IN 2019

2ML

4ML

SYNOLIS VA : PRODUCT RANGE

SYNVISC RANGE


SYNVISC

Manufacturer SANOFI

HA gel structure

SYNVISC contains hylan A (average molecular weight 6,000,000) and hylan B hydrated gel in a buffered physiological sodium chloride solution, pH 7.2. SYNVISC has an elasticity (storage modulusG') at 2.5 Hz of 111 ± 13 Pascals (Pa) and a viscosity (loss modulus G") of 25 ± 2 Pa (elasticity and viscosity of knee synovial fluid of 18 to 27-year-old humans measured with a comparable method at 2.5 Hz: G' = 117 ± 13 Pa; G" = 45 ± 8 Pa.)Each 2.25 mL syringe of SYNVISC contains:Hylan polymers (hylan A + hylan B) 16 mgSodium chloride 17 mgDisodium hydrogen phosphate 0.32 mgSodium dihydrogen phosphate monohydrate 0.08 mgWater for injection q.s. to 2.0 mL

IndicationsSYNVISC is indicated for the treatment of pain in osteoarthritis (OA) of the knee in patients who have failed to respond adequately to conservative nonpharmacologic therapy and simple analgesics, e.g., acetaminophen.

Pack size SYNVISC is supplied in a 2.25 mL glass syringe containing one 2 mL (16 mg) dose of SYNVISC. The contents of the syringe are sterile and nonpyrogenic.


SYNVISC ONE

Manufacturer SANOFI

HA gel structure

Synvisc-One combines the three doses of SYNVISC (SYNVISC) which consists of hylan A (average molecularweight 6,000,000 daltons) and hylan B hydrated gel in a buffered physiological sodium chloride solution, pH 7.2. Synvisc-One has an elasticity (storage modulus G') at 2.5 Hz of 111 ± 13 Pascals (Pa) and a viscosity(loss modulus G") of 25 ± 2 Pa (elasticity and viscosity of knee synovial fluid of 18 to 27- year-old humansmeasured with a comparable method at 2.5 Hz: G' = 117 ± 13 Pa; G" = 45 ± 8 Pa.)Each 10 mL syringe of Synvisc-One combines the three 2-mL doses (16 mg each) of a complete SYNVISC treatment regimen (48 mg). Each Synvisc-One 10-mL syringe contains:Hylan polymers (hylan A + hylan B) 48 mgSodium chloride 51 mgDisodium hydrogen phosphate 0.96 mgSodium dihydrogen phosphate monohydrate 0.24 mgWater for injection q.s. to 6.0 mL

Indications

Synvisc-One is indicated for the treatment of pain in osteoarthritis (OA) of the knee in patients who have

failed to respond adequately to conservative nonpharmacologic therapy and simple analgesics, e.g.,

acetaminophen.

Pack size Synvisc-One is supplied in a 10 mL glass syringe containing 3 doses (48 mg) of SYNVISC. The contents of the syringe are sterile and non-pyrogenic.


• Extensive bibliography

• Approved in most of worldwide countries, including USA and Japan

• Market leader in the majority of countries

• Supported by Sanofi

• Gold standard in 3 injection segment

• Global player: stable and homogeneous worldwide pricing strategy (upper end)

• For Synvisc-One, volume of 6ml: too large for knee joints

• Synvisc: NaHA from avian origin + chemical binding between chains not perceived as fully ethical & ecological responsive

• One of the highest price on the market (consistent across the world)

• Lack of product support, especially since it moved from Genzyme to Sanofi

• No novelties for many years

SYNVISC RANGE PROS & CONS

SYNOLIS RANGE VS SYNVISC RANGE


GENERAL COMPARISON

Product name Company

Mg of HA

HA origin

Crosslinked

Volume (ml) [ HA ] (%)

[HA] (mg/ml)

Molecular weight Regimen

Synvisc Sanofi 16 RC Y 2 0.8 8 6 MDa 1inj/ week3 weeks

Synolis VA Aptissen 40 B N 2 2 20 2 MDa 1 inj/week3 weeks or less

B: Biofermentation

RC: Rooster Combs

Y: Yes

N: No

Product name Company

Mg of HA

HA origin

Crosslinked

Volume (ml) [ HA ] (%)

[HA] (mg/ml)

Molecular weight Regimen

Synvisc One Sanofi 48 RC Y 6 0.8 8 6 MDa 1inj

Synolis VA Aptissen 80 B N 4 2 20 2 MDa 2 x 2 ml inj1 x 4ml inj


SAFETY

SYNVISC• Bellamy et al. compared Synvisc with Euflexxa in 321 patients over 3

months. 8% of patients who received Synvisc developed an effusion vs.0.6% for Euflexxa.

• Caborn et al. reported a level of adverse events comparable to thecomparator: triamcinolone hexacetonide (corticosteroid) with 7% ofinjection site-related events for Synvisc and 8% of swelling after injection.

• Raman et al. reported a case of pseudo-sepsis (major AE) in the groupusing Synvisc, along with minor adverse events in 39 patients out of 199(20%)

• The topic of increased adverse events associated with the use of Synvischas motivated further investigations and publications:

– Wadell et al.; J Surg Orthop Adv 2006; 15(1): 53-9

– Puttick et al.; J Rheumatol 1995; 22(7):1311-4

– Martens et al.; Arthritis Rheum 2001;44(4):978-9

– Leopold et al.; J Bone Jt Surg Am 2002;84-A(9):1619-23

– Magilavy et al.; J Bone Jt Surg Am 2003;85-A(8):1618-20

– Pullman-Mooar et al.; J Rheumatol 2002;29(12):2611-4

• A communication from Health Canada targeted the safety issue: http://www.hc-sc.gc.ca/dhp-mps/alt_formats/hpfb-dgpsa/pdf/medeff/carn-bcei_v15n2-eng.pdf

➔ Since then, the processes must have been optimized as there are lessadverse events in the clinical studies

SYNOLIS• Heisel et al. reported no adverse event reported by the 101 patients who

used GO-ON Matrix/Synolis V-A

• An observational study including 1147 patients using GO-ONMatrix/Synolis V-A (to be published) reported 22 patients with adverseevents (1.9%), the most common being “Injection site joint pain” (pain atinjection site that could result from the injection procedure).

➔ Synolis VA safety has always been flawless since the product is on themarket

http://www.hc-sc.gc.ca/dhp-mps/alt_formats/hpfb-dgpsa/pdf/medeff/carn-bcei_v15n2-eng.pdf

OBJECTIONS HANDLER


RHEOLOGICAL PROPERTIES OBJECTION

Synovial fluid is viscoelastic (meaning that it is viscous and elastic) and adapts its state to the speed of movement and constraint

Why is it important for the joint ?



100

10

1

0,1

0,01 0,1 1 10Frequency (HZ)

100

10

1

0,1

Elas

tici

ty G

’ (p

a)

Vis

cosi

ty G

’’ (

pa) Young

Wal

k

Ru

n

0.4 HzCROSSOVER

The dynamic moduli of synovial fluid from young and healthy patients (Balazs et al.)

What is the behavior of the viscosity and elasticity of the synovial fluid during a movement (measured by the frequency)?

The viscosity and elasticity meet at one point: crossover



Synolis VA is not crosslinked but its rheological properties are enhanced compare to young and healthy synovial fluid

• Better viscosity

• Better elasticity

• OBJECTION:

Synvisc had one of the highest elasticity and viscosity of products on the market

• HOW TO ANSWER:


HA PROTECTION RATE OBJECTION 1/2

Figure 1 : Protection of different HA against degradation

1. Aptissen SA - Geneva – Switzerland

Synolis VA is 3 to 4 times more resistant to degradation than other HA-containing products

• OBJECTION:

Synvisc and Synvisc-One are crosslinked and therefore it will be degraded more slowly

• HOW TO ANSWER:

0

10

20

30

40

50

60

70

80

90

100

0 2 4 6 8 10 12 14 16

Per

cen

tage

of

Elas

tici

ty (

%)

Degradation Time (min)

Synolis V-A Synvisc One

Resistance todegradation Cross-linked viscosupplement


HA PROTECTION RATE OBJECTION 2/2

Table 1 : Protection of different HA against degradation

• Sorbitol reduces the degradation of the gel by free radicals contained in OA joints

• Sorbitol protective effect is better than crosslinked

• Sorbitol preserves rheological properties of HA

• Synolis VA is 3 to 4 times more resistant to degradation than other HA-containing products 1

Formulation %ΔG’ (lost elasticity)

Synolis VA -22%

Cross-Linked -64%

1. Alexandre ADAMCZEWSkI Research department – Aptissen SA - Geneva – Switzerland


CARTILAGE OBJECTION

• OBJECTION:

Synvisc preserves cartilage

• HOW TO ANSWER:

Synvisc protects collagen (Type II) from degradation in OA patients

Synolis VA improves cartilage quality (C. Lavet et al Poster presented at ESCO 2017) and the high dose of sorbitol has a significant positive effect on chondrocyte viability (Mongkhon et al 2014)


STORAGE OBJECTION

• OBJECTION:

Why is Synolis VA storage temperature between 2ºC and 25ºC compared to Synvisc One that has higher ranges? (between 2ºC-30º)

• HOW TO ANSWER:

The storage temperature of Synolis VA is recommended to be room temperature (between 2ºC and 25ºC) in

order to maintain the rheological properties of the product.

Every product on the market has different manufacturing process or rheological properties which implies

differences in the storage.

synolis va vs synvisc · synolis va powered by aptissen - - aptissen private & confidential 5...

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