Distributed by:

Kaneka Pharma Europe N.V. German Branch

Frankfurter Straße 80 – 82

D-65760 Eschborn

Phone: +49 (0) 6196-96797-0

Fax: +49 (0) 6196-96797-29

E-Mail: contact@kaneka.de

www.kanekapharma.com

Manufactured by:

Kaneka Corporation

2-3-18, Nakanoshima Kita-ku

Osaka 530-8288

Japan

EC-representative:

Kaneka Pharma Europe N.V.

Nijverheidsstraat 16

2260 Westerlo-Oevel, Belgium

Phone: +32 (0) 14-256-297

Fax: +32 (0) 14-256-298

LA-15The adaptive apheresis therapy – safe, selective and efficient

0123 LA-1

5/E/

350/

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016

The adaptive LDL-apheresis therapy – safe, selective and effi cient

Mode of action of the LIPOSORBER® LA-15

A step further – Kaneka’s medical devices

Kaneka Corporation is one of the pioneers in the development and commercial launching of products for

therapeutic apheresis for lipid metabolism disorders (e.g. hyperlipidemia) and auto-immune diseases.

In 1986, Kaneka introduced the double-adsorber column LIPOSORBER® LA-15 apheresis system, which can be

regenerated for the repetitive use during a treatment.

Coronary heart diseases and the infl uence of blood lipids

Coronary heart diseases are characterised by chronic pro-

gressive changes in the blood vessel walls, infl uenced

by various factors such as lipoproteins, endothelial cells,

vascular smooth muscle cells, monocytes, macrophages,

thrombocytes, growth factors and cytokines. Known

independent risk factors for atherosclerosis development

include the various forms of hyperlipidemia including in-

creased lipoprotein(a), high blood pressure (hypertension),

diabetes mellitus, smoking, obesity and stress.

A meta-analysis of seventeen clinical studies on statins,

one of the world mostly used cholesterol-lowering drug,

demonstrates the effectiveness of statin-therapies on

stabilization the progression of coronary atherosclerosis (1).

With aggressive modifi cation of the risk factors and a lipid-

lowering therapy, it is possible to achieve not only plaque

stabilisation but even plaque regression.(1, 2, 3)

The therapeutic LDL-C goal by the apheresis: „The lower the better“

To achieve the therapeutic target, usually one has to resort

using a high dose statin therapy combined with other

medications.

If the therapeutic aims are not achieved by the applied

medications, one can start constructively with the effi cient

lipoprotein-apheresis therapy.

In addition to an effective reduction of LDL cholesterol

(LDL-C), the Lipoprotein-apheresis therapy is also able to

reduce the independent cardiovascular risk factor

lipoprotein(a) (Lp(a)), which does not respond adequately

to lipid-lowering medication.(4, 5, 6, 7, 8)

A step further – Kaneka’s medical devicesA step further – Kaneka’s medical devicesA step further – Kaneka’s medical devicesA step further – Kaneka’s medical devices

Kaneka Corporation is one of the pioneers in the development and commercial launching of products for Kaneka Corporation is one of the pioneers in the development and commercial launching of products for Kaneka Corporation is one of the pioneers in the development and commercial launching of products for Kaneka Corporation is one of the pioneers in the development and commercial launching of products for

LIPOSORBER® LA-15 – the safe double-adsorber regeneration system

LIPOSORBER® LA-15 system, enables

LDL-C reduction of up to 81%, with a

smaller extracorporeal volume as the

whole blood apheresis system with

LIPOSORBER® D. (12, 13, 14)

LIPOSORBER® LA-15 system therefore

offers an effi cient and safe therapeutic

option for sensitive patients with the indi-

cation of severe lipid metabolism disor-

ders, e.g. familial hypercholesterolemia or

increased Lp(a).(9 -13, 15, 16)

LIPOSORBER® LA-15 – selective adsorption

The adsorbent in LIPOSORBER® LA-15

columns is made of dextran sulfate-

cellulose beads, which provides specifi c

binding to Apo-B containing lipoproteins

such as LDL, VLDL and Lp(a). (See – Mode

of action of the LIPOSORBER® LA-15 (Fig.1)).

LDL, Lp(a) and VLDL are selectively

removed by the electro-static interaction

between the negatively charged dextran

sulfate and the positively charged moiety

of Apo-B. (9 – 13, 15, 16)

Therapeutic benefi ts

� Selective adsorption of LDL and

Lp(a) with a smaller extracorporeal

volume as the whole blood

LIPOSORBER® D system. (12 – 16)

� Provides an option to reach LDL-C

targets for high risk CV patients

according to ESC/EAS guidelines.

(12, 13, 15, 16, 23)

� Atherosclerosis stabilization and

plaque regression.(17, 18, 19)

� LIPOSORBER® LA-15 system offers

a safe, selective and effi cient

Lipoprotein-apheresis treatment.

(9 – 13, 15, 16)

Safety

� Safe to use and a well tolerated therapy. The safety of the treatment has been demonstrated in clinical studies. (9, 10, 11)

� LIPOSORBER® LA-15 System is certifi ed for CE-marking, approved in Japan, USA and Canada.

� The treatment set is made up of single-use components which are discard after every therapy.

Contraindication

ACE inhibitors are contraindicated, due

to the negatively charged surface of

LIPOSORBER® LA-15, and can be safely

replaced with AT-1 blockers. (9, 10, 11)

Cellulose beads

2 3

Fig. 1

The target: „the lower the better“

Figure 4 shows an optimal stepwise LDL-C reduction model for

high-risk patients during apheresis treatment. The target LDL-C

level for high-risk patients is below 70mg/dl (< 1.8 mmol/l).(23)

Therapeutic success – plaque stabilization and regressionLIPOSOBER® LA-15 – effi ciency by regeneration

Smaller extracorporeal volume

The column volume of one LIPOSORBER® LA-15 column is only

150 ml, which makes the total extracorporeal volume much

smaller as the whole blood LIPOSORBER® D system and

makes it possible to treat the patients gently.

Further reduction of the extracorporeal

volume is possible by using a smaller

plasma separator and removal of the

blood-warmer pouch in several

steps from 476 ml to 326 ml.

Patients with low body weight

particularly benefi t from this

fl exibility.

Use heparin to inhibit clotting in

the extracorporeal circuit.

Effi ciency by regeneration

Patient’s plasma is continuously pumped through LIPOSORBER®

LA-15 adsorber columns during the extracorporeal therapy.

Double-adsorber columns are alternately used for processing

plasma to adsorb atherogenic lipoproteins while the

other column is regenerated to recover its

adsorption capacity by fl ushing out the

adsorbed lipoproteins. This regenera-

tion procedure automatically takes

place without plasma loss and

ensures to reach the targeted

LDL-C value even in patients

with very high initial LDL-C.

A treatment session takes

approximately 2 to 4 hours and

is usually performed in an

out-patient clinic.

Air detector

Heparin pump

Blood pump Plasma pump

LIPOSORBER® LA-15Adsorption columns

Regenerationpump

Plasma separator

Blood return

Blood withdrawal

Blood return

Plasma line Waste lineHeater

Re-Primingsolution

Regenerationsolution

IVUS before initiating the LDL-apheresis IVUS after regular LDL-apheresis*Flow scheme – LIPOSORBER® LA-15 system

Diet

Time

Apheresis

LDL-

Chol

este

rol

Diet & Drug

Pre-treatment

Post-treatment

76%to81%

65%to69%

49%to60%

5%to14%

HDL-CTGLp(a)LDL-C

Low extracorporeal volumes

Patien

ts with low

body weight Sensitive p

atient

s w

ith

in

tole

ran

ces

RegenerationSele

ctiv

ity

Patie

nts with very high lipid concentrations

Fig. 2 (19)

Plaque Area = 7,8 mm2

Lumen Area = 3,3 mm2

Fig. 3 (19)

Plaque Area = 7,0 mm2

Lumen Area = 5,3 mm2

medio

Reduction rates by LIPOSORBER® LA-15Step-wise LDL-C lowering by Lipoprotein-apheresis therapy

Fig. 4 (24)

Fig. 5 (12)

4 5

The formula, according to Kroon et al., for calculating the time-averaged LDL-C concentration during biweekly treatment. (25)

* Statin plus apheresis therapy

Kaneka – for your healthThe LIPOSORBER® LA-15 Apheresis System

The apheresis monitoring machine, KANEKA MA-03*

KANEKA MA-03*, specially designed as

user-friendly, is used for plasma and

whole blood lipoprotein apheresis and

immuno-apheresis.

� High resolution 12 inch colour monitor

� Touch screen for direct interface

� Easy to use menu

� Integrated blood warmer

� Automatic blood pressure monitoring

� Records the treatment data on a

memory card

� MA-03* is CE-certifi ed

* manufactured by Nikkiso Co. Ltd.

LIPOSORBER® LA-15 at a glance

Safe:

� Proved by clinical studies (9, 10, 11)

� Used globally since 1986

� Regulatory approvals in the USA,

Canada, Japan and CE-marked

� Made up of disposables

Gentle:

� Smaller extracorporeal volume (14)

Effi cient:

� Selective elimination of atherogenic

lipoproteins (12, 13, 15, 16)

� No LDL adsorption capacity limit due

to the double-adsorber regeneration

procedure

References and Sources

1. Tian et al., 2012, BMC Cardiovas. Disord. Sep 1; 12:70. doi 10.1186/1471-2261-12-70

2. Nissen et al., 2006, ASTEROID trial, JAMA; 295(13):1556-65

3. Nissen et al., 2004, REVERSAL trial, JAMA; 291(9):1071-80

4. Julius et al., 2012, Therapeutic Apheresis and Dialysis; 17(2):179-184

5. Rosada et al., 2014, Artif. Org.; 38(2): 135–141

6. Leebmann et al., 2013, Circulation; 128(24):2567-76

7. Jaeger et al., 2009, Nature Clinical Practice Cardiovasc. Medicine; 6(3):229-239

8. Safarova et al., 2013, Atherosclerosis Supplement; 14:93-99

9. Palcoux et al., 2008, Therapeutic Apheresis and Dialysis; 12(3):195-201

10. Hudgins et al., 2008, Am. J. Cardiol.; 102:1199-1204

11. Koga 1999, Therapeutic Apheresis; 3(2):155-160

12. Gordon et al., 1998, Am. J. Cardiol.; 81:407-411

13. Hequet at al., 2010, Transfusion and Apheresis Science; 42:3-10

14. Julius et al., 2013, Clin. Lipidol.; 8(6):693-705

15. Parker, 1994, Chem. Phys. Lipids; 67/68, 331-338

16. Kanemitsu et al., 1998, Therapeutic Apheresis; 2(1):65-70

17. Mabuchi et al., 1998, Am. J. Cardiol.;81:1489-1495

18. Kroon et al., 1998, LAARS; Circulation;93:1826-1836

19. Matsuzaki et al., 2002, LACMART; J. Am. College Cardiol.; 40:220-7

20. Elicio et al., 1997, Artif. Org.; 21(4):334-5

21. Sinzinger et al., 2000, Thromb. Res.; 100:43-46

22. Kojima et al., 2001, Hypertens. Res.; 24:595-598

23. Reiner et al., 2011, European Heart Journal; 32, 1769–1818; ESC/EAS GUIDELINES

24. Kaneka Pharma America, „The LIPOSORBER® Patient Guide“ (modifi ed)

25. Kroon et al., 1996, Circulation; 93: 1826-35

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