ORPHAN DRUG EVIDENCE REQUIREMENTS FOR POSITIVE HTA RECOMMENDATIONS
ISPOR 10 November 2015
Meriem Bouslouk, PhD, MSc Pharmaceuticals Department Federal Joint Committee (G-BA) Germany
WHO IS TAKING CARE OF ME?
Slide 2 | © 2015 | Meriem Bouslouk, PhD 1 JANUARY 2011, AMNOG: FAIR PRICING FOR NEW PHARMACEUTICALS
6 months until a G-BA resolution
Slide 3 | © 2015 | Meriem Bouslouk, PhD
ADDITIONAL BENEFIT
Orphan drug ˂ €50 million
Extent of the additional benefit over the appropriate comparator:
1) Major additional benefit------
2) Considerable additional benefit 6) Non-quantifiable?
3) Minor additional benefit------
Probability of the 4) No additional benefit additional benefit: . Proof . Indication 5) Less benefit than . Hint the appropriate comparator
Slide 4 | © 2015 | Meriem Bouslouk, PhD EXTENT OF THE ADDITIONAL BENEFIT Highest category per AMNOG procedure Major (15 October 2015) 1 Reference price 4 Non-quantifiable 14 Considerable 30 Total of 139 resolutions
No additional Considerable benefit Minor 3 56 34
Non-quantifiable 10
Minor 13 26 orphan drugs
Slide 5 | © 2015 | Meriem Bouslouk, PhD
IMPORTANT MILESTONES IN THE ASSESSMENT
Active ingredient Therapeutic area Date of the G-BA resolution * Time-limited Pirfenidone Idiopathic pulmonary fibrosis 15 March 2012 Tafamidis meglumine Amyloidosis 7 June 2012 Pasireotide Hypopituitarism 6 December 2012 Ivacaftor Cystic fibrosis 7 February 2013 Ruxolitinib Myeloproliferative disorders 7 March 2013 Decitabine Leukemia, myeloid 2 May 2013 Hodgkin disease lymphoma, non- Brentuximab vedotin 16 May 2013 Hodgkin Bosutinib Leukaemia, myeloid 17 October 2013* Ponatinib Leukemia, lymphoid; myeloid 23 January 2014* Pomalidomide Multiple myeloma 20 February 2014 Macitentan Pulmonary hypertension 17 July 2014 Riociguat Pulmonary hypertension 16 October 2014 Digestive system diseases, Cholic acid 6 November 2014 metabolism, inborn errors Ruxolitinib (> €50m) Myeloproliferative disorders 6 November 2014
Slide 6 | © 2015 | Meriem Bouslouk, PhD IMPORTANT MILESTONES IN THE ASSESSMENT
Active ingredient Therapeutic area Date of the G-BA resolution * Time-limited Pirfenidone Idiopathic pulmonary fibrosis 15 March 2012 Tafamidis meglumine Amyloidosis 7 June 2012 Idiopathic pulmonary PasireotidePirfenidone Cushing’s disease 156 December March 2012 2012 Ivacaftorfibrosis Cystic fibrosis 7 February 2013 Ruxolitinib Myeloproliferative disorders 7 March 2013 Decitabine Leukemia, myeloid 2 May 2013 Hodgkin disease lymphoma, non- Brentuximab vedotin 16 May 2013 Hodgkin Bosutinib Leukaemia, myeloid 17 October 2013* Ponatinib Leukemia, lymphoid; myeloid 23 January 2014* Pomalidomide Multiple myeloma 20 February 2014 Macitentan Pulmonary hypertension 17 July 2014 Riociguat Pulmonary hypertension 16 October 2014 Digestive system diseases, Cholic acid 6 November 2014 metabolism, inborn errors Ruxolitinib (> €50m) Myeloproliferative disorders 6 November 2014
Slide 7 | © 2015 | Meriem Bouslouk, PhD
IMPORTANT MILESTONES IN THE ASSESSMENT
Active ingredient Therapeutic area Date of the G-BA resolution * Time-limited Pirfenidone Idiopathic pulmonary fibrosis 15 March 2012 Tafamidis meglumine Amyloidosis 7 June 2012 Pasireotide Hypopituitarism 6 December 2012 Ivacaftor Cystic fibrosis 7 February 2013 Ruxolitinib Myeloproliferative disorders 7 March 2013 Decitabine Leukemia, myeloid 2 May 2013 Hodgkin disease lymphoma, non- Brentuximab vedotin 16 May 2013 Hodgkin Bosutinib Leukaemia, myeloid 17 October 2013* Ponatinib Leukemia, lymphoid; myeloid 23 January 2014* Pomalidomide Multiple myeloma 20 February 2014 Macitentan Pulmonary hypertension 17 July 2014 Riociguat Pulmonary hypertension 16 October 2014 Digestive system diseases, Cholic acid 6 November 2014 metabolism, inborn errors Ruxolitinib (> €50m) Myeloproliferative disorders 6 November 2014
Slide 8 | © 2015 | Meriem Bouslouk, PhD IMPORTANT MILESTONES IN THE ASSESSMENT
Active ingredient Therapeutic area Date of the G-BA resolution * Time-limited Pirfenidone Idiopathic pulmonary fibrosis 15 March 2012 Tafamidis meglumine Amyloidosis 7 June 2012 Pasireotide Cushing’s disease 6 December 2012 Ivacaftor Cystic fibrosis 7 February 2013 RuxolitinibPasireotide Cushing’s Myeloproliferative disease disorders 67 March December 2013 2012 Decitabine Leukemia, myeloid 2 May 2013 Hodgkin disease lymphoma, non- Brentuximab vedotin 16 May 2013 Hodgkin Bosutinib Leukaemia, myeloid 17 October 2013* Ponatinib Leukemia, lymphoid; myeloid 23 January 2014* Pomalidomide Multiple myeloma 20 February 2014 Macitentan Pulmonary hypertension 17 July 2014 Riociguat Pulmonary hypertension 16 October 2014 Digestive system diseases, Cholic acid 6 November 2014 metabolism, inborn errors Ruxolitinib (> €50m) Myeloproliferative disorders 6 November 2014
Slide 9 | © 2015 | Meriem Bouslouk, PhD
IMPORTANT MILESTONES IN THE ASSESSMENT
Active ingredient Therapeutic area Date of the G-BA resolution * Time-limited Pirfenidone Idiopathic pulmonary fibrosis 15 March 2012 Tafamidis meglumine Amyloidosis 7 June 2012 Pasireotide Hypopituitarism 6 December 2012 Ivacaftor Cystic fibrosis 7 February 2013 Ruxolitinib Myeloproliferative disorders 7 March 2013 Decitabine Leukemia, myeloid 2 May 2013 Hodgkin disease lymphoma, non- Brentuximab vedotin 16 May 2013 Hodgkin Bosutinib Leukaemia, myeloid 17 October 2013* Ponatinib Leukemia, lymphoid; myeloid 23 January 2014* Pomalidomide Multiple myeloma 20 February 2014 Macitentan Pulmonary hypertension 17 July 2014 Riociguat Pulmonary hypertension 16 October 2014 Digestive system diseases, Cholic acid 6 November 2014 metabolism, inborn errors Ruxolitinib (> €50m) Myeloproliferative disorders 6 November 2014
Slide 10 | © 2015 | Meriem Bouslouk, PhD IMPORTANT MILESTONES IN THE ASSESSMENT
Active ingredient Therapeutic area Date of the G-BA resolution * Time-limited Pirfenidone Idiopathic pulmonary fibrosis 15 March 2012 Tafamidis meglumine Amyloidosis 7 June 2012 Pasireotide Cushing’s disease 6 December 2012 Ivacaftor Cystic fibrosis 7 February 2013 Ruxolitinib Myeloproliferative disorders 7 March 2013 Decitabine Leukemia, myeloid 2 May 2013 IvacaftorHodgkin Cystic disease fibrosis lymphoma, non- 7 February 2013 Brentuximab vedotin 16 May 2013 Hodgkin Bosutinib Leukaemia, myeloid 17 October 2013* Ponatinib Leukemia, lymphoid; myeloid 23 January 2014* Pomalidomide Multiple myeloma 20 February 2014 Macitentan Pulmonary hypertension 17 July 2014 Riociguat Pulmonary hypertension 16 October 2014 Digestive system diseases, Cholic acid 6 November 2014 metabolism, inborn errors Ruxolitinib (> €50m) Myeloproliferative disorders 6 November 2014
Slide 11 | © 2015 | Meriem Bouslouk, PhD
IMPORTANT MILESTONES IN THE ASSESSMENT
Active ingredient Therapeutic area Date of the G-BA resolution * Time-limited Pirfenidone Idiopathic pulmonary fibrosis 15 March 2012 Tafamidis meglumine Amyloidosis 7 June 2012 Pasireotide Cushing’s disease 6 December 2012 Ivacaftor Cystic fibrosis 7 February 2013 Ruxolitinib Myeloproliferative disorders 7 March 2013 Decitabine Leukemia, myeloid 2 May 2013 Hodgkin disease lymphoma, non- Brentuximab vedotin 16 May 2013 Hodgkin Bosutinib Leukaemia, myeloid 17 October 2013* Ponatinib Leukemia, lymphoid; myeloid 23 January 2014* Pomalidomide Multiple myeloma 20 February 2014 Macitentan Pulmonary hypertension 17 July 2014 Riociguat Pulmonary hypertension 16 October 2014 Digestive system diseases, Cholic acid 6 November 2014 metabolism, inborn errors Ruxolitinib (> €50m) Myeloproliferative disorders 6 November 2014
Slide 12 | © 2015 | Meriem Bouslouk, PhD IMPORTANT MILESTONES IN THE ASSESSMENT
Active ingredient Therapeutic area Date of the G-BA resolution * Time-limited Pirfenidone Idiopathic pulmonary fibrosis 15 March 2012 Tafamidis meglumine Amyloidosis 7 June 2012 Pasireotide Cushing’s disease 6 December 2012 Ivacaftor Cystic fibrosis 7 February 2013 Ruxolitinib Myeloproliferative disorders 7 March 2013 Decitabine Leukemia, myeloid 2 May 2013 Hodgkin disease lymphoma, non- Brentuximab vedotin 16 May 2013 Hodgkin BosutinibBosutinib Leukaemia, Leukaemia, myeloid myeloid 17 October October 2013* 2013* Ponatinib Leukemia, lymphoid; myeloid 23 January 2014* Pomalidomide Multiple myeloma 20 February 2014 Macitentan Pulmonary hypertension 17 July 2014 Riociguat Pulmonary hypertension 16 October 2014 Digestive system diseases, Cholic acid 6 November 2014 metabolism, inborn errors Ruxolitinib (> €50m) Myeloproliferative disorders 6 November 2014
Slide 13 | © 2015 | Meriem Bouslouk, PhD
IMPORTANT MILESTONES IN THE ASSESSMENT
Active ingredient Therapeutic area Date of the G-BA resolution * Time-limited Pirfenidone Idiopathic pulmonary fibrosis 15 March 2012 Tafamidis meglumine Amyloidosis 7 June 2012 Pasireotide Cushing’s disease 6 December 2012 Ivacaftor Cystic fibrosis 7 February 2013 Ruxolitinib Myeloproliferative disorders 7 March 2013 Decitabine Leukemia, myeloid 2 May 2013 Hodgkin disease lymphoma, non- Brentuximab vedotin 16 May 2013 Hodgkin Bosutinib Leukaemia, myeloid 17 October 2013* Ponatinib Leukemia, lymphoid; myeloid 23 January 2014* Pomalidomide Multiple myeloma 20 February 2014 Macitentan Pulmonary hypertension 17 July 2014 Riociguat Pulmonary hypertension 16 October 2014 Digestive system diseases, Cholic acid 6 November 2014 metabolism, inborn errors Ruxolitinib (> €50m) Myeloproliferative disorders 6 November 2014
Slide 14 | © 2015 | Meriem Bouslouk, PhD IMPORTANT MILESTONES IN THE ASSESSMENT
Active ingredient Therapeutic area Date of the G-BA resolution * Time-limited Pirfenidone Idiopathic pulmonary fibrosis 15 March 2012 Tafamidis meglumine Amyloidosis 7 June 2012 Pasireotide Cushing’s disease 6 December 2012 Ivacaftor Cystic fibrosis 7 February 2013 Ruxolitinib Myeloproliferative disorders 7 March 2013 Decitabine Leukemia, myeloid 2 May 2013 Hodgkin disease lymphoma, non- Brentuximab vedotin 16 May 2013 Hodgkin Bosutinib Leukaemia, myeloid 17 October 2013* Ponatinib Leukemia, lymphoid; myeloid 23 January 2014* Leukemia, lymphoid; PomalidomidePonatinib Multiple myeloma 2023 February January 2014 2014* Macitentanmyeloid Pulmonary hypertension 17 July 2014 Riociguat Pulmonary hypertension 16 October 2014 Digestive system diseases, Cholic acid 6 November 2014 metabolism, inborn errors Ruxolitinib (> €50m) Myeloproliferative disorders 6 November 2014
Slide 15 | © 2015 | Meriem Bouslouk, PhD
IMPORTANT MILESTONES IN THE ASSESSMENT
Active ingredient Therapeutic area Date of the G-BA resolution * Time-limited Pirfenidone Idiopathic pulmonary fibrosis 15 March 2012 Tafamidis meglumine Amyloidosis 7 June 2012 Pasireotide Cushing’s disease 6 December 2012 Ivacaftor Cystic fibrosis 7 February 2013 Ruxolitinib Myeloproliferative disorders 7 March 2013 Decitabine Leukemia, myeloid 2 May 2013 Hodgkin disease lymphoma, non- Brentuximab vedotin 16 May 2013 Hodgkin Bosutinib Leukaemia, myeloid 17 October 2013* Ponatinib Leukemia, lymphoid; myeloid 23 January 2014* Pomalidomide Multiple myeloma 20 February 2014 Macitentan Pulmonary hypertension 17 July 2014 Riociguat Pulmonary hypertension 16 October 2014 Digestive system diseases, Cholic acid 6 November 2014 metabolism, inborn errors Ruxolitinib (> €50m) Myeloproliferative disorders 6 November 2014
Slide 16 | © 2015 | Meriem Bouslouk, PhD IMPORTANT MILESTONES IN THE ASSESSMENT
Active ingredient Therapeutic area Date of the G-BA resolution * Time-limited Pirfenidone Idiopathic pulmonary fibrosis 15 March 2012 Tafamidis meglumine Amyloidosis 7 June 2012 Pasireotide Cushing’s disease 6 December 2012 Ivacaftor Cystic fibrosis 7 February 2013 Ruxolitinib Myeloproliferative disorders 7 March 2013 Decitabine Leukemia, myeloid 2 May 2013 Hodgkin disease lymphoma, non- Brentuximab vedotin 16 May 2013 Hodgkin Bosutinib Leukaemia, myeloid 17 October 2013* Ponatinib Leukemia, lymphoid; myeloid 23 January 2014* Pomalidomide Multiple myeloma 20 February 2014 Macitentan Pulmonary hypertension 17 July 2014 Riociguat Pulmonary hypertension 16 October 2014 Digestive system diseases, CholicRuxolitinib acid Myeloproliferative 6 November 2014 metabolism, inborn errors (> €50m) 6 November 2014 Ruxolitinib (> €50 m) disordersMyeloproliferative disorders 6 November 2014
Slide 17 | © 2015 | Meriem Bouslouk, PhD
IMPORTANT MILESTONES IN THE ASSESSMENT
Active ingredient Therapeutic area Date of the G-BA resolution * Time-limited Elosulfase alfa Mucopolysaccharidosis IVA 20 November 2014 Siltuximab Giant lymph node hyperplasia 4 December 2014 Cabozantinib Thyroid neoplasms 22 January 2015* Obinutuzumab Leukemia, lymphocytic, chronic 5 February 2015 Teduglutide Malabsorption syndromes 19 February 2015 Ivacaftor Cystic fibrosis 19 February 2015 (new indication) Mantle-cell lymphoma Ibrutinib 16 April 2015 leukaemia, lymphocytic, chronic Alipogene tiparvovec Lipoprotein lipase deficiency 21 May 2015* Ataluren Muscular Dystrophy, Duchenne 21 May 2015* Pasireotide Acromegaly 18 June 2015 (new indication) Ramucirumab Stomach Neoplasms 16 July 2015 Nintedanib Idiopathic Pulmonary Fibrosis 3 September 2015 Eliglustat Gaucher Disease 1 October 2015
Slide 18 | © 2015 | Meriem Bouslouk, PhD IMPORTANT MILESTONES IN THE ASSESSMENT
Active ingredient Therapeutic area Date of the G-BA resolution * Time-limited Elosulfase alfa Mucopolysaccharidosis IVA 20 November 2014 Siltuximab Giant lymph node hyperplasia 4 December 2014 Cabozantinib Thyroid neoplasms 22 January 2015* Obinutuzumab Leukemia, lymphocytic, chronic 5 February 2015 Teduglutide Malabsorption syndromes 19 February 2015 Ivacaftor Cystic fibrosis 19 February 2015 (new indication) Mantle-cell lymphoma Ibrutinib 16 April 2015 leukaemia, lymphocytic, chronic Alipogene tiparvovec Lipoprotein lipase deficiency 21 May 2015* AlipogeneAtalurenLipoprotein Muscular Dystrophy, lipase Duchenne 21 May 2015* 21 May 2015* Pasireotide tiparvovec deficiencyAcromegaly 18 June 2015 (new indication) Ramucirumab Stomach Neoplasms 16 July 2015 Nintedanib Idiopathic Pulmonary Fibrosis 3 September 2015 Eliglustat Gaucher Disease 1 October 2015
Slide 19 | © 2015 | Meriem Bouslouk, PhD
EVIDENCE AND OUTCOME
Active Evidence basis for the No of patients Extent of No of patients ingredient assessment assessed additional in Germany (intervention/control) Benefit (highest) (SHI) Pirfenidone 2 RCTs (double-blind, placebo- 174/174; Non- 6,000 control, phase 3) 171/173 quantifiable Tafamidis 1 RCT (placebo-control, double-blind, 65/63 Minor 40-100 meglumine phase 2/3) Pasireotide 1 randomised uncontrolled, double- 82/80 Minor 160-360 blind, phase 3 trial Ivacaftor 2 RCTs (active control, double-blind, 83/78; 26/26 Considerable 170 (2 subpopulations) phase 3) Ruxolitinib 2 RCTs (placebo-control, double- 155/154 Minor 1,600-5,000 2 assessments: blind, phase 3; active control, ˂ €50m 146/73 Considerable > €50m open-label, phase 3)
Decitabine 1 RCT (active control, open-label 242/243 Minor 300-780 phase 3) Brentuximab 1 uncontrolled phase 2 trial; phase 1 182/--; 42/-- Non-quantifiable 60-260 vedotin trials and case series 15-160 (2 indications, 3 subpopulations) Bosutinib 1 uncontrolled single arm phase 52/-- Non- 380-500 1/2 trial quantifiable Ponatinib 1 uncontrolled, single arm open-label 444/-- Non-quantifiable 525-1,135 (2 indications) phase 2 trial
red: Assessments also available in UK and France
Slide 20 | © 2015 | Meriem Bouslouk, PhD EVIDENCE AND OUTCOME
Active Evidence basis for the No of patients Extent of No of patients ingredient assessment assessed additional in Germany (intervention/control) Benefit (highest) (SHI) Pomalidomide 1 RCT (active control, open-label, 302/153 Considerable 1,900 phase 3) Macitentan 1 RCT (placebo-control, double- 242/249 Minor 580-5,850 blind, phase 3) Riociguat 1 RCT (placebo-control, double- 133/88 Minor 580-7,850 blind, phase 3) Cholic acid Case series, literature review 52/-- Non-quantifiable 10-25
Elosulfase alfa 1 RCT (placebo-control, double- 58/59 Minor 15-95 blind, phase 3) Cabozantinib 1 RCT (placebo-control, double- 219/111 Minor 60-500 blind, phase 3) Obinutuzumab 1 RCT (active control, open-label, 333/330 Non-quantifiable 818-1,477 phase 3) Teduglutide 2 RCTs (placebo-control, double- 43/43; 35/16 Minor 1,100-2,400 blind, phase 3)
Ivacaftor 1 RCT (placebo-control, double- 38/37 Minor 10-11 (new indication) blind, phase 3)
red: Assessments also available in UK and France
Slide 21 | © 2015 | Meriem Bouslouk, PhD
EVIDENCE AND OUTCOME
Active ingredient Evidence basis for the No of patients Extent of additional No of patients assessment assessed Benefit (highest) in Germany (intervention/control) (SHI)
Ibrutinib 2 RCTs (placebo-control, 111/---; 195/196 Non-quantifiable 700-950 (2 indications, 3 double-blind, phase 3; active- subpopulations) 2,000-7,500 control, double-blind, phase 3) 200-300
Alipogene tiparvovecData review 9/- Non-quantifiable 17-35
Ataluren 1 RCT (placebo-control, 57/57 Minor 82-110 double-blind, phase 2b)
Pasireotide 1 RCT (active control, double 65/65/68 Minor 265- 1,133 (new indication) blind, phase 3)
Ramucirumab 1 RCT (placebo control, 330/335 Minor 5,900-7,900 double blind, phase 3)
Nintedanib 2 RCTs (placebo control, 309/204; 329/219 Minor 2,080-19,700 double blind, phase 3)
Eliglustat 1 RCT (active control, open 34/53 Non-quantifiable 150-500 label, phase 3)
Slide 22 | © 2015 | Meriem Bouslouk, PhD www.g-ba.de