Canada’s  Orphan  Drug  Regulatory  Framework:  What  Health  Canada  is  doing  now  and  what  is  yet  to  come      Canadian  Expert  Pa.ents  in  Health  Technology  Conference  November  7,  2016    Liz  Anne  Gillham-­‐Eisen  Health  Products  and  Food  Branch  

Orphan  drugs  

Orphan  drugs  are  used  to  treat  rare  diseases  which:  •  are  life-­‐threatening,  seriously  debilita.ng  or  both  serious  and  chronic  in  nature  

•  affect  a  rela.vely  small  number  of  pa.ents  (less  than  5  in  10  000,  but  typically  closer  to  1  in  100  000)  

•  are  oRen  gene.cally  based,  onset  at  birth  or  early  childhood,  lead  to  a  shortened  life-­‐span  

•  reduce  quality  of  life  and  place  significant  challenges  on  pa.ents,  caregivers  and  the  healthcare  system  

•  are  difficult  to  study  because  of  the  small  pa.ent  popula.on  

 

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Challenges:  Limited  pa?ent  popula?ons  and  treatments      

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There are more than 7,000 rare diseases

Rare diseases affect 1 in 12, or nearly 3 million Canadians

Diagnosis is challenging and can take years

Once diagnosed, there is likely no treatment available, or limited treatments for the patient

Challenges  –  Orphan  drug  development  and  pa?ent  access  

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Orphan  drugs  are  challenging  to  develop:  

Small  pa.ent  popula.ons  make  it  difficult  to  conduct  clinical  trials,  especially  in  na.ons  without  large  pa.ent  popula.ons  

LiXle  is  oRen  known  about  the  rare  disease  

Researchers  and  drug  sponsors,  in  the  past,  did  not  have  incen.ves  to  invest  in  developing  drugs  for  rare  diseases  

Once  developed  and  approved:

Orphan  drugs  are  oRen  costly  

Pa.ents  across  Canada  may  not  have  equal  access  to  approved  orphan  drugs  

An  Orphan  Drug    Framework  for  Canada  A  Regulatory  Framework  for  Drugs  for  Rare  Diseases  (Orphan  Drugs)  proposed  to  -­‐      

• channel  orphan  drugs  into  a  federal  regulatory  pathway  designed  to  improve  market  availability  in  Canada    • draw  on  new  post-­‐market  and  transparency  powers  from  Vanessa’s  Law      • reflect  Canada’s  legisla.ve  and  regulatory  context,  while  aligning  where  possible  with  other  interna.onal  regulators’  orphan  drug  frameworks    • encourage  the  genera.on  of  knowledge  regarding  rare  diseases  in  drug  development  through  an  open  and  transparent  regulatory  environment  and  the  provision  of  advice  to  companies  developing  orphan  drugs    • allow  for  accelerated  market  authoriza.on    

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Life-­‐cycle  Approach  What  is  known  about  the  poten?al/actual  benefits,  harms  and  uncertain?es  associated  with  a  drug  changes  over  ?me    

Current:    Limited  point-­‐in-­‐,me  oversight  based  on  applica.ons  for  clinical  trials  and  marke.ng  authoriza.ons.    

Future:    Expanded  and  con,nuous  oversight  beginning  at  early  development  stage  with  medical  plausibility  and    encompassing  a  greater  ability  to  define  post-­‐approval  informa.on  gathering.    

Transparency  throughout  the  life  cycle  

More  collabora.on  with  other  health  system  partners,  such  as  HTA  Agencies  

 

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Key  Components  of  the  Framework  Defini?on  Orphan  drugs  are  used  to  treat  rare  diseases  which:  

• are  life-­‐threatening,  seriously  debilita.ng  or  both  serious  and  chronic  in  nature  • affect  a  rela.vely  small  number  of  pa.ents  (less  than  5  in  10  000)    

Orphan  drug  designa?on  cer?ficate  

• publicly  iden.fy  medically  plausible  orphan  drugs  to  enable  early  considera.on  of  medically  plausible  drugs  by  payers  for  purposes  of  improving  pa.ent  access    

 

Regulator’s  Advice  • wriXen  regulator’s  advice  for  clinical  trials,  the  poten.al  balance  of  pre-­‐  and  post-­‐market  evidence  requirements,  and  the  development  of  post-­‐market  plans  • joint  advice  where  possible  with  interna.onal  regulators  and  HTA  bodies    

   

Key  Components  of  the  Framework  Market  Authoriza?on  Applica?ons  • modernized  licensing  structure  and  possibility  for  abbreviated  pathway  for  ultra-­‐rare  orphan  drugs  • ability  to  issue  terms  and  condi.ons  on  a  market  authoriza.on  • post-­‐authoriza.on  plan  to  characterize,  monitor  and  con.nue  to  iden.fy,  assess  and  manage  the  harms  and  benefits  associated  with  the  orphan  drug  

–  includes:  enhanced  post-­‐market  surveillance  procedures,  regular  monitoring  of  terms  and  condi.ons  of  market  authoriza.on,  risk  management  plan,  confirmatory  studies,  etc.    

Transparency  

• Transparency  throughout  the  life-­‐cycle  of  the  drug  to  communicate  applica.ons  under  review  and  regulatory  review  decisions.  

Pa?ent  Involvement  • Collec.on  and  considera.on  of  public  input  into  the  review  of  submissions  for  orphan  drugs.      

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Regulatory  Openness  and  Transparency  •  To  help  Canadians  beXer  understand  how  and  why  decisions  are  

made:  –  Submissions  Under  Review  

•  hXp://www.healthycanadians.gc.ca/drugs-­‐products-­‐medicaments-­‐produits/authorizing-­‐manufacturing-­‐autorisa.on-­‐fabrica.on/review-­‐approvals-­‐evalua.on-­‐approba.ons/submissions-­‐under-­‐review-­‐presenta.ons-­‐cours-­‐examen-­‐eng.php  

–  Drug  and  Health  Products  Register  •  hXps://hpr-­‐rps.hres.ca/  

–  Regulatory  Decision  Summary  (RDS)  –  purpose  and  reason  •  hXp://www.hc-­‐sc.gc.ca/dhp-­‐mps/prodpharma/rds-­‐sdr/drug-­‐med/index-­‐eng.ph  

–  Summary  Basis  of  Decision  (SBD)  –  more  technical  than  RDS  •  hXp://www.hc-­‐sc.gc.ca/dhp-­‐mps/prodpharma/sbd-­‐smd/drug-­‐med/index-­‐eng.php  

–  Summary  Safety  Reviews  •  hXp://www.hc-­‐sc.gc.ca/dhp-­‐mps/medeff/reviews-­‐examens/ssr-­‐rei-­‐eng.ph  

–  Stakeholder  Registry  •  hXp://www.hc-­‐sc.gc.ca/ahc-­‐asc/public-­‐consult/stakeholder-­‐intervenants/index-­‐

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Pa?ent  Involvement:  Exploring  opportuni?es  •  Pa.ent  input  can  add  value  to  the  evalua.on  of  human  drugs,  such  as  

contribu.ng  to  benefit/risk  assessment  •  Current  approach  considered  “ad-­‐hoc”.  Pa.ents  as  part  of  expert  

commiXees  or  panels;  part  of  specific  issues,  and  rou.nely  as  part  of  policy  and  regulatory  development.  Health  Canada  is  currently    exploring  and  examining  the  most  effec.ve  ways  to  involve  pa.ents  in  the  review  process  

•  Not  a  ques.on  of  “if”  but  a  ques.on  of  “how”  •  Consulta.on  with  pa.ents,  pa.ent  groups,  caregivers  and  health  care  

providers  cri.cal  for  the  design  of  any  program(s)    

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Pa?ent  Involvement  Pilot  Project  •  Pa.ent  Involvement  pilot  project  launched  in  2014  

•  Orphan  drugs  context  was  considered  a  good  star.ng  point  •  Pilot  was  intended  to  be  a  simula.on  of  how  input  could  be  obtained  and  

used  to  help  inform  Health  Canada’s  benefit/risk  assessment    •  Two  drugs  were  involved  in  the  pilot  (one  biologic  and  one  pharmaceu.cal)  

•  Input  was  sought  through  online  ques.onnaires  designed  to  gather  the  perspec.ves  of  pa.ents,  caregivers,  pa.ent  groups  and  health  care  professionals.  Ques.ons  related  to  quality  of  life,  experience  with  other  therapies,  unmet  need,  and  risk  tolerance.    

•  Results  –  more  experience  is  needed;  reviewer  and  pa.ent  group  training  would  be  useful,  .ming  of  request  for,  and  receipt  of  input  is  important,  considera.on  should  be  given  to  establishing  criteria  for  when  to  request  pa.ent  input  that  would  be  of  most  value  to  both  reviewers  and  pa.ents.    

Finding the right balance

Who best to provide input?

When most feasible and

useful to collect?

What other information

could be collected?

Most effective and best format/s: summaries?

Other?

How best to use the

input?

Accountability

Routine collection or establish criteria for

when most valuable?

Meaningful data and timeliness of reviews

Vanessa’s  Law  •  Overall  policy  objec.ves  are  to:  

–  Provide  a  range  of  pre-­‐  and  post-­‐market  regulatory  tools  that  enable  the  safety  oversight  of  therapeu.c  products  throughout  their  lifecycle;  and  

–  Promote  greater  confidence  in  the  oversight  of  therapeu.c  products  by  increasing  transparency.  

 

•  Vanessa’s  Law  amends  the  Food  and  Drugs  Act    improving  Health  Canada’s  ability  to:    –  collect  post-­‐market  safety  informa.on    –  take  appropriate  ac.on  when  a  serious  risk  to  health  is  iden.fied    

•  These  amendments  are  par.cularly  important  in  the  rare  disease  context  where  oRen  .mes:  –  many  of  the  pa.ents  impacted  are  vulnerable  paediatric  popula.ons    –  informa.on  on  the  drug  and  the  disease  is  some.mes  limited    

 

 

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Vanessa’s  Law  •  June  18,  2016:  No.ce  of  Intent  that  Health  Canada  plans  to  bring  

forward  regulatory  amendments  to  implement  key  authori.es  under  Vanessa’s  Law  

Coming  soon  

•   Two  regulatory  packages  are  under  development:  –  Authori.es  to  implement  a  lifecycle  approach  to  regula.ng  drugs  

(“Vanessa’s  Law  Lifecycle  Authori.es”)  –  Recall  of  drugs  and  medical  devices  

Coming  later  •  Analysis  con.nues  on  the  other  Vanessa’s  Law  authori.es  (terms  and  

condi.ons  for  market  authoriza.ons,  repor.ng  of  adverse  reac.ons,  and  disclosure  of  clinical  trial  informa.on)    

 

 

Current  availability  of  Orphan  Drugs  in  Canada  •  Patented  Medicine  Prices  Review  Board's  (PMPRB)  Orphan  

Drug  Launch  Monitor,  published  in  2016:      

–  analyzes  the  interna.onal  approval  of  designated  orphan  drugs  and  assesses  their  availability  in  Canada  

–  focuses  on  a  number  of  select  orphan  drugs  reported  at  the  ac.ve-­‐substance  level  and  iden.fied  based  on  the  following  criteria:  1.  drugs  that  received  orphan  designa.on  and  approval  in  the  US  and/or  EU  over  the  last  

decade  (2005–2014),  and  2.  drugs  that  only  have  orphan  indica.ons  

–  includes  Canada  and  the  seven  PMPRB  interna.onal  comparator  countries  (PMPRB7):  France,  Germany,  Italy,  Sweden,  Switzerland,  the  United  Kingdom  (UK)  and  the  US  

 

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The  PMPRB  analysis  reveals  the  following  key  points:  

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Many orphan drugs available in PMPRB7 countries are approved for use in Canada

Health Canada approved 9 of the top 10 select orphan drugs

Orphan drugs not available in Canada represent a small share of the international market: some were accessed through the Special Access Program, while others were approved by Health Canada in 2015

Access  to  drugs  as  a  priority  

  Minister  of  Health  mandate  leXer  (2015)  •  “…improve  access  to  necessary  prescrip.on  

medicines”  

  HPFB  priori.es  –  new  Strategic  Plan  

Research & development

Health Canada review / authorization

Patented Medicine Prices Review Board

(PMPRB)

Health Technology Assessment

Provincial/Territorial Drug Plans

 

pan-Canadian  Pharmaceu?cal  Alliance  

(pCPA)  

   

Hospitals

Patient Access

  Innova.on  and  access  to  drugs  -­‐  What  role  can  the  regulator  play?  

Private Plans

Where do we go from here?

•  Improving  research,  approval,  and  access  •  Many  of  the  tools  considered  for  orphan  drugs  can  also  

be  considered  in  the  context  of  all  drugs    •  Work  is  ongoing  to  explore  and  examine  most  effec.ve  

ways  to  involve  pa.ents  in  the  review  process  •  Life  cycle  approach  and  increasing  transparency  •  Con.nue  collabora.ons  interna.onally  to  promote  

convergence,  and  enhance  collabora.ons  among  key  Canadian  stakeholders  across  the  lifecycle  of  a  drug  

       Thank  You/Merci!  

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