Resolution by the Federal Joint Committee on an amendment to the Pharmaceutical Directive (AM-RL): Appendix XII - Resolutions on the benefit assessment of pharmaceuticals with new active ingredients, in accordance with the German Social Code, Book Five (SGB V), section 35a Pomalidomide from 20 February 2014 In its session on 20 February 2014, the Federal Joint Committee resolved to amend the Pharmaceutical Directive (AM- RL), version published 18 December 2008/22 January 2009 (Federal Gazette, number 49a of 31 March 2009), last amended on 6 February 2014 (Federal Gazette, AT 27 February 2014 B3), as follows: Appendix XII shall be amended in alphabetical order to include the active ingredient pomalidomide: Pomalidomide Therapeutic indication I. Imnovid in combination with dexamethasone is indicated in the treatment of adult patients with relapsed and refractory multiple myeloma who have received at least two prior treatment regimens, including both lenalidomide and bortezomib, and have demonstrated disease progression on the last therapy. 1. Extent of additional benefit of the pharmaceutical Pomalidomide is authorized as a pharmaceutical for the treatment of a rare disease (orphan drug) in accordance with EC regulation number 141/2000 of the European Parliament and Council of 16 December 1999 on orphan drugs. In accordance with SGB V section 35a, paragraph 1, sentence 10, the additional medical benefit has been proved through market authorization. In accordance with the rules of procedure of the Federal Joint Committee, chapter 5, section 12, paragraph 1, number 1, sentence 2, the Federal Joint Committee determines the extent of the additional benefit for the number of patients and patient groups for whom a therapeutically significant additional benefit exists. This quantification of the additional benefit has been conducted in accordance with the criteria laid out in the Rules of Procedure, chapter 5, section 5, paragraph 7, numbers 1 to 4. Extent of additional benefit: Considerable Study results according to endpoints 1, 2 : Mortality Intervention arm (pomalidomide + low-dosage dexamethasone) Overall survival (OS) Control arm (high-dosage dexamethasone) N=302 3 N=153 3 Following median follow-up period of 18.1 weeks 4 Deaths OS in weeks Deaths OS in weeks Intervention vs. control HR [95% CI] 76 (25.2%) n.r. [48.1; n.r.] 58 (37.9%) 34.0 [23.4; 39.9] 0.53 [0.37; 0.74] p<0.001 1 2 3 4 Data for the CC-4047-MM-003 study target population from the G-BA benefit assessment, the dossier of the pharmaceutical company, and the publication San Miguel et al. (2013). If not otherwise indicated, the results at data cut-off on 7 September 2012 (median follow-up period: 18.1 weeks) are shown. ITT population: all randomized patients. Data cut-off: 7 September 2012; crossover rate: 29%.
Intervention arm (pomalidomide + low-dosage dexamethasone) Following median follow-up period of 10.0 months 5 Morbidity OS in months Progress -free survival (PFS) Progress/death Control arm (high-dosage dexamethasone) OS in months Intervention vs. control HR [95% CI] AD 12.7 [10.4; 15.5] 8.1 [6.9; 10.8] HR=0.74 [0.56; 0.97] p=0.0285 AD: 4.6 months Weeks Median [95% CI] Progress/death Weeks HR [95% CI] AD 164 (54.3%) 15.7 [13.0; 20.1] 103 (67.3%) 8.0 [7.0; 9.0] 0.45 [0.35; 0.59] p<0.001 AD: 7.7 weeks Health-related quality of life 6 EORTC QLQ-30: No significant differences on 13 of 15 subscales. On subscale physical function difference in favor of pomalidomide; on subscale nausea and vomiting difference not in favor of pomalidomide. EORTC QLQ-MY20 and EQ 5D: no significant differences. Side effects 8 AE SAE AE CTC grade 3 or 4 N=300 7 N=149 7 OR [95% CI] 291 (97.0%) 139 (93.3%) 2.33 [0.92; 5.85] p=0.0814 153 (51.0%) 75 (50.3%) 1.03 [0.69; 1.52] p=0.9204 234 (78.0%) 113 (75.8%) 1.13 [0.71; 1.80] p=0.6332 Discontinuation of treatment due to AE 29 (9.7%) 8 (5.4%) 1.89 [0.84; 4.23] p=0.1454 AE of particular interest 9 CTC grade CTC grade OR [95% CI] 10 All grades Neutropenia 3 or 4 All grades 3 or 4 10 136 (45.3%) 125 (41.7%) 29 (19.5%) 22 (14.8%) 4.123 [2.482; 6.849] p<0.0001 5 6 7 8 9 Data cut-off: 1 March 2013; crossover rate: 50%. Metrics used: EORTC QLQ-30, EORTC QLQ-MY20, EQ 5D. All randomized patients who have received at least one dose of the study medication. Patients with at least one event. AEs of particular interest discussed in the EPAR are shown.
10 Applies to AE of CTC grade 3 or 4. OR or for AEs of all grades were not available.
Intervention arm (pomalidomide + low-dosage dexamethasone) Thrombocytopenia Infection Control arm (high-dosage dexamethasone) Intervention vs. control 81 (27.0%) 62 (20.7%) 40 (26.8%) 36 (24.2%) 0.818 [0.512; 1.305] p=0.3985 165 (55.0%) 72 (24.0%) 72 (48.3%) 34 (22.8%) 1.068 [0.671; 1.701] p=0.8144 Haemorrhage 49 (16.3%) 8 (2.7%) 32 (21.5%) 7 (4.7%) 0.556 [0.198; 1.563] p=0.2734 Venous thromboembolic event 10 (3.3%) 4 (1.3%) 3 (2.0%) 0 n/a p=0.3068 Peripheral neuropathy 37 (12.3%) 3 (1.0%) 16 (10.7%) 2 (1.3%) 0.742 [0.123; 4.491] p=0.6686 Secondary primary malignoma Other selected AEs 2 (0.7%) 11 1 (0,7%) 11 0,993 [0,089; 11,04] p=1.000 Diseases of the blood and lymphatic system 209 (69.7%) 176 (58.7%) 85 (57.0%) 68 (45.6%) n.a. Febrile neutropaenia 20 (6.7%) 20 (6.7%) 0 (2.0%) 0 n/a p=0.0004 Leukopaenia 37 (12.3%) 26 (8.7%) 8 (5.4%) 5 (3.4%) 2.732 [1.027; 7.266] p=0.0465 Metabolic and nutritional disorders 95 (31.7%) 48 (16.0%) 60 (40.3%) 29 (19.5%) n.a. Hyperglycaemia Insomnia Myopathy 15 (5.0%) 9 (3.0%) 12 (8.1%) 10 (6.7%) 0.430 [0.171; 1.082] p=0.0814 24 (8.0%) 1 (0.3%) 31 (20.8%) 4 (2.7%) n.a. 2 (0.7%) 0 (0.0%) 11 (7.4%) 5 (3.4%) n.a. Abbreviations used: AD: absolute difference; CTCAE: common terminology criteria for adverse events; HR: hazard ratio; ITT: intention to treat; n.a.: not available; n: number of patients with event; N: total number of patients; n/a: not applicable; n.r.: not reached; OR: odds ratio; (S)AE: (serious) adverse events 2. Number of patients and criteria for defining patients eligible for treatment Target population: approx. 1,900 patients 11 Non-invasive basal-cell carcinoma of the skin.
3. Requirements for quality-assured administration The specifications outlined in the product information are to be followed. The European Medicines Agency (EMA), the European regulatory authority, provides the product information for Imnovid (active ingredient: pomalidomide) at the following public link (last accessed: 15 January 2014): http://www.ema.europa.eu/docs/en_gb/document_library/epar_-_product_information/human/002682/wc500147717.pdf Treatment with pomalidomide must be initiated and monitored by an internist for haematology and oncology experienced in the treatment of patients with multiple myeloma. The prescribing physician must inform female and male patients of teratological risks expected and the strict contraception measures described in the contraception programme and provide them with materials in accordance with the national patient card system. Treatment with pomalidomide should be discontinued if the disease progresses. 4. Costs of treatment Duration of treatment: Pomalidomide (Patients 75 years and older) (Patients 75 years and older) Consumption: Mode of treatment 1 x 4 mg daily on 21 days of a 28-day cycle 1 x 40 mg daily on days 1, 8, 15 and 22 of a 28-day cycle 1 x 20 mg daily on days 1, 8, 15 and 22 of a 28-day cycle Strength (mg) Number of treatments per patient per year Duration per treatment (days) Number of treatment days per patient per year 13 cycles 21 273 13 cycles 4 52 13 cycles 4 52 Number/amount per pack (tablets) 12 Average annual consumption (tablets) Pomalidomide 4 21 273 (Patients 75 years and older) 8 100 260 (Patients 75 years and older) 8 100 130 Costs: Cost of pharmaceutical: Costs (pharmacy retail price) Cost after legally mandated rebates Pomalidomide 12,997.64 12,360.08 [ 1.80 13 ; 635.76 14 ] 15 123.07 112.40 [ 1.80 13 ; 8.87 14 ] "Lauer-Taxe", effective: 1 January 2014 Costs for additional, necessary statutory health insurance (SHI) benefits: None Annual treatment costs: Annual treatment costs per patient Pomalidomide in combination with dexamethasone (Patients 75 years and older) 160,973.28 Pomalidomide in combination with dexamethasone (Patients 75 years and older) 160,827.16 12 13 14 15 Largest pack. Rebate in accordance with SGB V, section 130. Rebate in accordance with SGB V, section 130a. Reference price.
II. This resolution takes effect on the day of its publication in the internet on the website of the Federal Joint Committee on 20 February 2014. The justification for this resolution will be published on the website of the Federal Joint Committee at www.g-ba.de. Berlin, 20 February 2014 The Federal Joint Committee in accordance with SGB V, section 91 The Chair Hecken