April	  15,	  2012	                                  	                                  	          Strategic	  Clinical	  ...
Candida	  Fratazzi	  MD	                                      President                                            	      ...
Learning	  Objec1ves                                                	          •  Understand	  drug	  development	  challe...
Innova1ve	  Strategies	  are	  overdue	  4	  
Which	  are	  the	  causes                                                         	          •  Gaps,	  that	  cost	  1me...
S t r a t e g y 	   a n d 	   I n n o v a 1 o n 	  6	  
Bridging	  research	  and	  clinical	  trials                                                           	  Focus	  on	  cl...
Strategic	  Clinical	  Innova1on	  is	  a	  bridge	          •  Links	  preclinical	  data	  with	  unmeet	  medical	     ...
                                                          Bridging	  the	  Chasm	                                         ...
S t r a 1 fi e d 	   M e d i c i n e 	   i s 	   t h e 	   g o a l 	  10	  
Choose	  the	  RIGHT	  DRUG	  at	  the	  RIGHT	  DOSE	  for	             the	  RIGHT	  GROUP	  OF	  PEOPLE      	         ...
          Beneficial	  to	  some	                       	  12	  
Harmful	  to	  others                               	  13	  
Advantages	  of	  Stra1fied	  Medicine	  •             Avoid	  adverse	  events	                   Ø  2.2	  million	  peop...
B i o m a r k e r s 	   a r e 	   t h e 	   t o o l s 	  15	  
Why	  Biomarkers	  are	  important                                             	  16	  
Biomarker	  defini1on	             A	  molecule	  that	  indicates	  	  an	  altera1on	  of	             the	  physiologica...
Biomarkers	  connect                                           	                          Qualified	  biomarkers           ...
Different	  types	  of	  biomarkers                                                          	           •  Screening	  mar...
Different	  types	  of	  biomarkers                                                        	           •  Stra:fica:on	  mar...
Biomarkers	  in	  clinical	  innova1on	                                   •      Biomarkers	  that	  validate	  the	  impo...
O r p h a n 	   D i s e a s e 	   i s 	   t h e 	   m o d e l : 	                              C a s e 	   S t u d y 	  22...
Gaucher	  disease	  Type	  1	                                                  	           Challenge	           Develop	  ...
Gaucher	  disease	  Type	  1	                                                  	           Strategy	  	           Create	 ...
Gaucher	  Disease	           •  Rare	  disease	  with	  a	  	  prevalence	  1:50,000-­‐	  100,000;	              Type	  1	...
Gaucher	  Disease	           •  Inherited	  deficiency	  of	  lysosomal	  enzyme	              glucocerebrosidase	  (GCD)	 ...
Gaucher	  Disease	  type	  1	  -­‐	  Clinical	  Features                                                                  ...
Study	  Endpoints                                              	           •  Change	  from	  baseline	  	               –...
Summary	           The	  proposed	  clinical	  strategy	  was	  successful,	           	  and	  the	  product	  was	  appr...
                               Clinical	  Strategy	  Success                                                            	 ...
C o n c l u s i o n 	  31	  
Safer	  and	  more	  Effec1ve	  drugs                                                	  32	  
Strategic	  Clinical	  Innova1on	  approach	                                                                	           • ...
Strategic	  Clinical	  Innova1on	  advantages                                                               	           • ...
Q u e s t i o n s 	     	     ? 	   ? !35	  
Disclosure	                                                	                                                	             ...
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ACRP 2012 Global Conference & Exhibition


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The Rising Interest in the Rare Disease Model Could Have a Critically Important Role into Biomarker’s Implementation for Stratified Medicine.

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ACRP 2012 Global Conference & Exhibition

  1. 1. April  15,  2012       Strategic  Clinical  Innova1on  1  
  2. 2. Candida  Fratazzi  MD   President   BBCR,  LLC   www.bostonclinicalresearch.com   S023  room  350  D-­‐F     10:30-­‐  11:30AM     Rising  interest  in  the  Rare  Disease  model  could  have    a  cri1cal  role  into  Biomarker’s  implementa1on     for  Stra1fied  Medicine  2  
  3. 3. Learning  Objec1ves   •  Understand  drug  development  challenges   •  Biomarkers  per  pa1ents  selec1on  and  efficacy   evalua1on:  an  orphan  disease  case  study     •  Discuss  strategic  clinical  innova1on  and  stra1fied   medicine  3  
  4. 4. Innova1ve  Strategies  are  overdue  4  
  5. 5. Which  are  the  causes   •  Gaps,  that  cost  1me  and  money,  appear  in  the  clinical   research  process     •  Protocols  wriVen  for  top  line  visualiza1on  that  may  be   lacking  scien1fic  rigor   •  Clinical  strategies  and  plans  may  be  myopic  and  miss   greater  op1ons   •  Increasing  regulatory  demand  for  transparent  study   results  and  cross  AEs  5  
  6. 6. S t r a t e g y   a n d   I n n o v a 1 o n  6  
  7. 7. Bridging  research  and  clinical  trials  Focus  on  clinical  strategy,  early  plan  and  study  design   7  
  8. 8. Strategic  Clinical  Innova1on  is  a  bridge   •  Links  preclinical  data  with  unmeet  medical   needs   •  Matches  study  endpoints  with  study  objec1ves   •  Connects  product  poten1al  to  treatment   benefits   •  Creates  cohesive  phase  I/II  studies  to  support   first  in  man/POC  objec1ves  8  
  9. 9.   Bridging  the  Chasm     Pre-­‐clinical  research  meets  FPI     Protocol  Synopsis   Trial  Design   Biomarkers   Protocol  Implementa:on/ Discovery  /  Pre-­‐Clinical   Objec1ves/   Endpoints   Safety  /   Tox  Data   Pa1ents   Selec1on   CRO   Strategy   Discovery   Pa1ents   Data   Safety   Disease   Regula1on   Pa1ents’   Staging/   Needs   KOL  9  
  10. 10. S t r a 1 fi e d   M e d i c i n e   i s   t h e   g o a l  10  
  11. 11. Choose  the  RIGHT  DRUG  at  the  RIGHT  DOSE  for   the  RIGHT  GROUP  OF  PEOPLE   Responders Non-Responders Adverse Drug Events 11  
  12. 12.   Beneficial  to  some    12  
  13. 13. Harmful  to  others  13  
  14. 14. Advantages  of  Stra1fied  Medicine  •  Avoid  adverse  events   Ø  2.2  million  people  are  hospitalized  and  100,000   deaths  occur  each  year  due  to  adverse  effects  of   prescrip1on  drugs  •  BeFer  treat  disease   Ø  Development  of  predic1ve  markers  would  allow  for   earlier  treatment  •  Iden:fy  novel  drug  targets   Ø   Current  drugs  are  based  on  less  than  500  targets     14  
  15. 15. B i o m a r k e r s   a r e   t h e   t o o l s  15  
  16. 16. Why  Biomarkers  are  important  16  
  17. 17. Biomarker  defini1on   A  molecule  that  indicates    an  altera1on  of   the  physiological  state  of  an  individual  in     rela1onship  to  health  or  disease  state,     drug  treatment,  toxins  etc.              Biomarkers  are,  by  virtue  of  their  short  term  availability,   predictors  of  long  term  events  17  
  18. 18. Biomarkers  connect   Qualified  biomarkers   Biology   Clinical     endpoints     A qualified biomarker must link biology and clinical end-points18  
  19. 19. Different  types  of  biomarkers   •  Screening  markers:  markers  discrimina1ng  the   healthy  state  from  beginning  of  disease  state   preferen1ally  in  an  asymptoma1c  phase  (  cancer   makers  for  early  diagnos1c)   •  Prognos:c  markers:  once  the  disease  state  is   established  predict  the  likely  course  of  the  disease      19  
  20. 20. Different  types  of  biomarkers   •  Stra:fica:on  markers:  predict  the  likelihood  of  a   response    to  a  drug  before  star1ng  treatment   classifying  pa1ents  in   responders  and   non-­‐ responders   •  Efficacy  markers:  monitor  the  efficacy  of  a  drug   treatment    20  
  21. 21. Biomarkers  in  clinical  innova1on   •  Biomarkers  that  validate  the  importance  of  the  target  in  Target  Valida1on   human  disease          Target/Compound   •  Biomarkers  that  define  the  direct  interac1on  of  the  Interac1on   compound  with  its  discrete  target        Pharmacodynamic   •  Biomarkers  that  define  consequences  of  compound  Ac1vity  (PK/PD)   interac1on  with  the  target  rela1ve  to  PK        Disease  Biomarker  &  Disease  Modifica1on   •   Biomarkers  that  correlate  with  disease            Pa1ent  selec1on  and   •   Biomarkers  that  define  likelihood  of  pa1ents  to  respond  Stra1fica1on   21   (or  not)  to  the  compound  
  22. 22. O r p h a n   D i s e a s e   i s   t h e   m o d e l :   C a s e   S t u d y  22  
  23. 23. Gaucher  disease  Type  1     Challenge   Develop  the  new  ERT  in  an  orphan  popula1on  when  a   very  similar  product  had  the  market  monopoly  for  about   15  years   •  Very  limited  number  of  naïve  pa1ents   •  Newly  diagnosed  pa1ents  presented  with  early   symptoms   •  Treated  pa1ents  had  improvement  on  many  of  the   clinical  features  23  
  24. 24. Gaucher  disease  Type  1     Strategy     Create  a  clinical  innova1ve  strategy  and  trial  designs,   which  would  require  a  feasible  number  of  pa1ents,  and   1ght  pa1ents’  selec1on  with  study  endpoints.  Select   validated  biomarkers’  assay  with  known  intra-­‐assay  and   intra-­‐personal  variability.  Work  with  the  Regulatory   agency  upfront  to  validate  approach.  Understand   physicians  and  pa1ents  expecta1ons  versus  current   standards  of  care.  24  
  25. 25. Gaucher  Disease   •  Rare  disease  with  a    prevalence  1:50,000-­‐  100,000;   Type  1  is  the  most  common  Gaucher  variant   •  Disease  expression  varies  from  asymptoma1c  to   significant  morbidity   •  Disease  progression  in  Type  1  Gaucher  disease  occurs   over  decades,  possibly  shortens  life  expectancy    25  
  26. 26. Gaucher  Disease   •  Inherited  deficiency  of  lysosomal  enzyme   glucocerebrosidase  (GCD)   •  Accumula1on  of  glucocerebroside  in  macrophage   lysosomes  (liver,  spleen,  bone  marrow,  brain)   •  3  variants:  type  1,  2,  and  3  26  
  27. 27. Gaucher  Disease  type  1  -­‐  Clinical  Features  •  Hepatosplenomegaly  •  Hypersplenism  •  Hematological  abnormali1es  (anemia,   thrombocytopenia)  •  Lung  disease  •  Bone  disease  (pain  crises,  fractures,  osteonecrosis)    •  Non-­‐neuronopathic  (Types  2  &  3  are  neuronopathic)    27  
  28. 28. Study  Endpoints   •  Change  from  baseline     –  Hemoglobin   –  Platelet  count   –  Spleen  volume   –  Liver  volume  28  
  29. 29. Summary   The  proposed  clinical  strategy  was  successful,    and  the  product  was  approved    29  
  30. 30.   Clinical  Strategy  Success     •  Overall  clinical  development  program  well  planned   •  Clinically  meaningful  endpoints   –  Natural  history  well  understood     •  Each  trial  had  a  dis1nct  purpose   –  studies  supported  an1cipated  use  in  both   treatment  naïve  and  switching  pa1ents  30  
  31. 31. C o n c l u s i o n  31  
  32. 32. Safer  and  more  Effec1ve  drugs  32  
  33. 33. Strategic  Clinical  Innova1on  approach     •  Develop  Early  Roadmap     •  Create  Strategic  Clinical  Plan   •  Customize  trial  design   •  Op1mize  pa1ent  selec1on   •  Visualize  goals,  ac1on  plan  and  op1ons   •  Maximize  early  stage  product-­‐value  33    
  34. 34. Strategic  Clinical  Innova1on  advantages   •  Accelerate  enrolment   •  Increase  inves1gators’    interest   •  Facilitate  IRB  approval   •  Reduce  pa1ents  withdrawn  from  the  study   •  Reduce  blames  for  bad  trial  execu1on   •  Increase  study  success  rate    34  
  35. 35. Q u e s t i o n s     ?   ? !35  
  36. 36. Disclosure       I  have  no  relevant  financial  rela1onship     in  rela1on  to  this  educa1onal  ac1vity  36