BioFreedom – the world’s first coronary stent system coated with BA9

Presentación del tema: "BioFreedom – the world’s first coronary stent system coated with BA9"— Transcripción de la presentación:

1 BioFreedom – the world’s first coronary stent system coated with BA9
BioFreedom – the world’s first coronary stent system coated with BA9. No polymer just stent and drug – no carriers, no permanent polymers or biodegradable polymers. The next natural progression in the development of the BioMatrix family of stents.

2 Qué es Biofreedom?

3 BioFreedom™: El primer DCS con BA9 que combina las ventajas de un DES y un BMS
Plataforma del stent Acero inoxidable 316 L Grosor del strut 0.0044” Perfil 0.043” (3.0mm) Polímero Sin portador polimérico del fármaco Fármaco Biolimus A9™ Dosis Dosis standard: 15.6µg de BA9/mm de longitud Cinética de Liberación 50 horas /90% liberado BioFreedom – the same stainless steel platform as BioMatrix Flex / Neo Flex which is 96%-98% free of drug at 28 days and as such becomes BMS stent-like around 28 days. The safety of a BMS with the effectiveness of a DES – giving you options for all your patients not just those who can take long DAPT regimens. I LIKE!

4 BioFreedom BioFreedom con BA9 sin polímero – Una combinación que ofrece al cardiólogo clínico la oportunidad de adaptar la TDAP para reducir el riesgo de sangrado

5 BioFreedom™: El primer DCS con BA9 que combina las ventajas de un DES y un BMS
Hipótesis: La liberación de la droga sín polímero vía stents porosos puede reducir los eventos tardíos causados por el polímero que recubre los stents. La superficie micro estructurada almacena el fármaco en los reservorios de la superficie abluminal. Ventajas potenciales: Evita los efectos tardíos de largo plazo que pudieran ser atribuibles al polímero L a integridad de la superficie presenta una mejora ya que no hay polímero que se pueda fracturar ó pelar La terapia dual antiplaquetaria pudiera acortarse BioFreedom – the same stainless steel platform as BioMatrix Flex / Neo Flex which is 96%-98% free of drug at 28 days and as such becomes BMS stent-like around 28 days. The safety of a BMS with the effectiveness of a DES – giving you options for all your patients not just those who can take long DAPT regimens. I LIKE!

6 La inflamación debida al polímero puede afectar la seguridad y la eficacia a largo plazo
Evidence has been accumulating over recent years demonstrating that durable polymer coatings on DES can lead to chronic inflammation and impaired healing. Biosensors developed the successful BioMatrix Flex / NeoFlex system, which addressed this issue and now we come to the market with a drug only coated stent – completely polymer free, a system we attest offers new options when it comes to selecting the right DAPT regime for all your patients. Inflammatory polymers have been shown to cause endothelial dysfunction in pre-clinical and clinical models1, 2, 3, 4 Dysfunctional endothelium can lead to vasoconstriction, increased inflammation, increase potential for thrombosis and delayed healing 5, 6, 7 The hypothesis is that an inflammatory polymer increases the potential for dysfunctional endothelium which may increase the potential for TLR and VLAST 1) Data from Abbott XIENCEV US Physician presentation SE D 2) Data on File at MDT - In vitro data verifying biocompatibility of BioLinx. Ref. Lab Notebooks 1813LAB (Carol Sullivan), 1816LAB & 1715LAB (Jennifer Wong). Ref. slides 15, 16 & 17 of TCTMD ) 3) Poster by Kishore Udipi: Development of a Novel Biocompatible Co-Polymer System for Extended Drug Release in a Second Generation Drug Eluting Stent Coverage 4) Awata et al. ACC 5) JW Kim et al. ACC 2008. 6) Data on File at MDT - Haraguchi et al. TCT ACH Challenge for Driver, Endeavor, Cypher, Taxus 7) PS 406 (ACH Challenge for Endeavor Resolute and Xience V)

7 Con BioFreedom 98% del fármaco está liberado del stent después de 1 mes
BA9 is proven to deliver BMS-like reendothilisation at 28 days. The Biofreedom stent is 98% free of drug at 28days. Biosensors conclude there is a high possibility that BioFreedom is the first stent with the efficacy of a DES and the safety of a BMS

8 El precio de la TDAP: Sangrado ?
As all of the studies have shown, DAPT brings not only increased efficacy but also an increase in major bleeding. Not all of these bleeding episodes need to be fatal but all will bring with them some form of mortality No significant p-values

9 ¿Es seguro el Biofreedom?

10 Evaluación Pre-clínica de seguridad
SAFETY Pre-clinical safety evaluation was conducted comparing two doses of Biolimus and demonstrated the following - we compared high (225µg BA9) and low (112µg BA9) dose Bio-Freedom (HD,LD) to a polymer-coated sirolimus eluting Cypher stent (SES) and a bare metal stent (BMS) at 28 and 180 days in an overstretch coronary mini-swine model.  Endpoints were histomorphometry and histology. At 28 days, there was a reduction in percent area stenosis by HD, LD and SES compared to BMS (% area stenosis: HD 17.67±4.01, LD 17.45±5.08, SES 16.40±3.89, BMS 26.74±12.37 %, BMS > HD, LD & SES, p=0.001). At 180 days, both Bio-Freedom stents were associated with reduced neointimal hyperplasia, whereas SES exhibited increased neointima (% area stenosis: HD 21.07±4.42, LD 20.00±5.44, SES 33.83±11.15, BMS 28.57±9.28 %, SES > HD & LD, BMS > HD & LD, p<0.001). At 180 days, SES showed increased fibrin and giant cells as well as a trend to more granulomas than the other groups.

11 Evaluación Pre-clínica de seguridad
SAFETY Pre-clinical safety evaluation was conducted comparing two doses of Biolimus and demonstrated the following - we compared high (225µg BA9) and low (112µg BA9) dose Bio-Freedom (HD,LD) to a polymer-coated sirolimus eluting Cypher stent (SES) and a bare metal stent (BMS) at 28 and 180 days in an overstretch coronary mini-swine model.  Endpoints were histomorphometry and histology. At 28 days, there was a reduction in percent area stenosis by HD, LD and SES compared to BMS (% area stenosis: HD 17.67±4.01, LD 17.45±5.08, SES 16.40±3.89, BMS 26.74±12.37 %, BMS > HD, LD & SES, p=0.001). At 180 days, both Bio-Freedom stents were associated with reduced neointimal hyperplasia, whereas SES exhibited increased neointima (% area stenosis: HD 21.07±4.42, LD 20.00±5.44, SES 33.83±11.15, BMS 28.57±9.28 %, SES > HD & LD, BMS > HD & LD, p<0.001). At 180 days, SES showed increased fibrin and giant cells as well as a trend to more granulomas than the other groups.

12 48 meses de resultados Todos los pacientes – 1er and 2da Cohorte (93
EVENTO BFD SD N = 60 BFD LD N = 62 TAXUS MACE (Muerte, IM, Bypass de emergencia ó TLR) 8(13.6%) 14(23.4%) 8(13.3%) Muerte 3(5.1%) 5(8.6%) 2(3.4%) IM 2(3.5%) 2(3.3%) 1(1.7%) IM con onda Q 0(0.0%) IM sin onda Q Bypass de emergencia TLR 3(5.2%) 8(13.2%) 6(10.2%) Trombosis del stent (Definitiva /Probable (ARC) At 48 months there was no  significant difference in MACE and TLR between the 3 studied groups and neither group had any ST events (reinforcing that techniques drive a reduction in ST even with old technology) All p-values are non-significant. Tests were performed for BFD SD vs. TAXUS and BFD LD vs. TAXUS.

13 ¿Es efectivo el Biofreedom?

14 Evaluación Pre-clínica de eficacia
There was no significant difference between either high dose or low dose, however, at 28 days both doses demonstrated significantly reduced neointimal thickness at 28 days vs BMS Tada et al., Circ Cardiovasc Interv 2010;3;

15 Evaluación Pre-clínica de eficacia
There was no significant difference between either high dose or low dose, however, at 28 days both doses demonstrated significantly reduced neointimal thickness at 28 days vs BMS Tada et al., Circ Cardiovasc Interv 2010;3;

16 Pérdida tardía del lumen(LLL) intra-stent a 12 meses de seguimiento 2da Cohorte – Endpoint primario
P = 0.001* (p=0.11**) P = 0.21* (p=0.55**) As the SD BioFreedom significantly reduced LLL versus Taxus at 12 months it became the standard dose for BioFreedom N = 31 N = 35 N = 31 *Non-inferiority tests based on the mean. **Superiority tests. All values are presented as median [IQR]. Grube E., oral presentation, TCT 2010

17 BioFreedom Comparable LLL Efficacy
BioFreedom LLL compared to Taxus ( LLL) FIM trial Xience - Stone GW. ACC2007 Spirit III Nevo – Ormiston et al. Circ Cadiovasc Interv 2010;3:556-64 BioMatrix Flex - The Lancet, Volume 372, Issue 9644, Pages , 27 September 2008

18 Revascularización de la lesión tratada (TLR) a 4 años
- 49%

19 ¿Cuál es el mensaje?

20 BioFreedom BioFreedom: primer y único stent libre de polímero liberador de BA9 Ningún polímero ofrece una reducida disfuncionalidad del endotelio BioFreedom FIM demostró una excelente eficacia con 49% RRR en TLR comparado con Taxus a 12 meses y no inferioridad (con tendencias hacia la superioridad) en términos de perdía tardía del lumen (LLL) intra-stent No hay incidencia de trombosis del stent definitiva / probable hasta 4 años en pacientes tratados con BioFreedom Gracias al perfil de liberación y a la ausencia de polímero, Biofreedom es igual de efectivo que un BMS después de un mes, incluso puede ser apropiado recomendar una TDAP más corta Esta hipótesis está siendo probada en el estudio clínico LEADERS-Free BioFreedom is the  first polymer-free drug coated stent with BA9 (Biolimus), BioFreedom FIM demonstrated the excellent efficacy profile of BioFreedom with 49% RRR in TLR compared to Taxus at 12 months and non-inferiority (with a numerical improvement and trend towards superiority) in terms of In-Stent LLL. There was no incidence of definite / probable stent thrombosis (ARC) up to 4 years for the patients treated with BioFreedom. Due to drug elution profile, and absence of polymer, at 1 month BioFreedom is effectively a BMS and therefore a shorter DAPT recommendation may be appropriate, this hypothesis is currently being tested in a large RCT – LEADERS-Free. A drug coated stent that allows shorter DAPT with the benefit of a limus drug to regulate the healing process, could also demonstrate a significant reduction in bleeding episodes, if as in the FIM Leaders Free shows no ST events associated with BioFreedom and shorter DAPT is shown to reduce bleeding episodes, then we have a product here that can change the world of PCI with metal stents!

21 Más datos

22 Biosensors believe in BioFreedom and we have invested heavily to get the answers everyone is asking about optimal DAPT. The data from this study will be available in 2015.

23 Estudio LEADERS Free, un diseño único
Double blinded design in a DES trial PI: Philip Urban Estudio Randomizado, Prospectivo, multi-centro, multi-nacional, doble ciego Población con alto riesgo de sangrado (ACS + Pacientes estables electivos) Población selectiva 2500 pacientes en 65 hospitales a nivel mundial BioFreedom™ DCS 1:1 aleatorización Gazelle™ BMS Seguimiento clínico: 1 m 2 m 4 m año años Endpoint primario de seguridad: Composición de muerte cardiaca, IM, trombosis del stent definitiva/probable a 1 año (No-inferioridad) Endpoint primario de eficacia: TLR clínicamente indicada a 1 año (Superioridad) TDAP obligatoria solamente por 1 mes, seguida de TSAP por un largo plazo Leaders Free will answer this question. It is double blinded, randomized, looking at high bleeding risk forgotten patients in 65 centres worldwide – 2500 recruited April 2014 Primary safety endpoint - Composite of cardiac death, MI, definite/probable stent thrombosis at 1 year (Non-inferiority) Primary efficacy endpoint - Clinically driven TLR at 1 year (Superiority) Dos endpoints primarios de seguridad y eficacia 1 mes de Terapia Dual Antiplaquetaria (DAPT) Urban et al., Am Heart J. 2013; 165:

24 Pacientes « olvidados » Un stent metálico libre de polímero
Tendencia actual en la terapia dual: « más corta es mejor » Urban, oral presenation, EuroPCR 2012

25 Importancia del estudio
Primer estudio de un DCS de gran escala que se fija “endpoints” clínicos Primer estudio prospectivo, randomizado, doble ciego que evalúa el uso de un stent activo con sólo un mes de TDAP Primer estudio prospectivo, randomizado, doble ciego que evalúa resultados en pacientes sometidos a PCI considerados de alto riesgo de sangrado

26 ¿Cómo puede impactar el estudio Leaders Free en la práctica clínica ?
Definirá los riesgos relativos de la trombosis del stent y de sangrado en un subgrupo de pacientes complejos. Podrá ayudar a “desconectar” la idea del uso de stents activos con una TDAP prolongada e ininterrumpida. Tiene el potencial de demostrar que los pacientes con alto riesgo de sangrado pueden beneficiarse de las bajas tasas de TLR. Read the slide !

27 ¿Qué más se está llevando a cabo?

28 BioFreedom EGO Biofreedom Pre-IDE Study in the US
OCT Study Hong Kong Pre-IDE Study in the US Inició en Junio 2014 BioFreedom Japan registration study Otros ?????

29 GRACIAS