DETERMINANTS OF ORPHAN DRUG PRICES IN FRANCE: REGRESSION ANALYSIS

Transcription

1 DETERMINANTS OF ORPHAN DRUG PRICES IN FRANCE: REGRESSION ANALYSIS Korchagina D 1, Vataire AL 2, Toumi M 3, Falissard B 4, Aballéa S 2 ISPOR 18th Annual European Congress 1 University of Paris-Sud, Paris, France, 2 Creativ-Ceutical, Paris, France, 3 Aix- Marseille University, Marseille, France, 4 Maison de Solenn, Paris, France

2 Background

3 Orphan drugs Rare diseases About 7000 diseases, mostly genetic and very severe conditions Low prevalence Little interest from the industry Low profitability High unmet needs Special orphan legislation USA 1983: Orphan Drug Act EU 2000: Regulation (EC) No 141/2000 (the Orphan Regulation) Japan 1993: Orphan drug regulation Singapore 1991: Medicine Order Orphan Drug Exemption Australia 1997: Orphan Drug Policy Taiwan 2000: Rare Disease and Orphan Drug Act - 3 -

4 Revenue OD prices Price per patient Targeted population size Ultra-orphan product Orphan product Specialist product GP product OD market is very heterogeneous: Revenue Covered therapeutic areas Geographical regions - 4 -

5 HTA in France Transparency Committee (CT) Assessment of actual benefit (AB), improvement in actual benefit (IAB), target population Health Technology Assessment French National Authority for Health (HAS) Economic and Public Health Assessment Committee (CEESP) Health economic assessment National Union of Health Insurance Funds (UNCAM) Reimbursement rate Pricing & Reimbursement Decision Economic Committee for Healthcare Products (CEPS) Price negotiation with pharmaceutical company Ministry of Health (MoH) Inclusion in hospital list and reimbursement list Publication in the Official Journal AB main driver for reimbursement IAB main driver for price: I Therapeutic breakthrough II Important improvement in terms of efficacy or safety III Modest improvement in terms of efficacy or safety IV Minor improvement in terms of efficacy or safety V No improvement - 5 -

6 Methods

7 Data extraction Therapeutic area (EPAR) Prevalence (orphan designation) Population age (EPAR) Severity (Orphan designation) Alternative treatments (HTA report) ATC class (EPAR) Treatment line (HTA report) MA date (EPAR) Posology Disease Drug Type of the pilot study (HTA report) Nb of patients in the study (HTA report) Comparator (HTA report) Endpoint (hard vs. surrogate) (HTA report) Evidence AB score (HTA report) IAB score (HTA report) HTA date (HTA report) Commercialisation date (Ameli database) Price (ex-factory, retail) (Ameli database) Reimbursement level (Ameli database) Delay between MA and commercialization HTA

8 Data extraction Therapeutic area (EPAR) Prevalence (orphan designation) Population age (EPAR) Severity (Orphan designation) Alternative treatments (HTA report) ATC class (EPAR) Treatment line (HTA report) MA date (EPAR) Posology Disease Drug Type of the pilot study (HTA report) Nb of patients in the study (HTA report) Comparator (HTA report) Endpoint (hard vs. surrogate) (HTA report) Evidence AB score (HTA report) IAB score (HTA report) HTA date (HTA report) Commercialisation date (Ameli database) Price (ex-factory, retail) (Ameli database) Reimbursement level (Ameli database) Delay between MA and commercialization HTA

9 Methods Descriptive analyses Bivariate analyses Regression analyses Cost as continuous variable: GLM (goodness of fit tested with RMSE) Gamma distribution Negative binomial distribution All analyses were conducted SAS

10 Results

11 Nb of assessments Availability of ODs in France Approved by EMA 102 Assessed by HAS 91 On the market 79 Price is available HTA Year

12 Percent Annual treatment cost 70 observations Average cost = , ranging from to Cost Orfadin, Fabrazyme, Replagal Vpriv Kalydeco Soliris Myozyme Increlex Carbaglu Aldurazyme Naglazyme Elaprase Cost

13 Frequency Annual cost, Is cost driven by the IAB score? T = 1.43 p = (38%) 6 (9%) 14 (21%) 15 (22%) 7 (10%) IAB score IAB score Most of ODs were assigned IAB II by the HAS. No significant association between the IAB score and the cost

14 Annual cost Is cost driven by the prevalence? Average prevalence: 1.23 per individuals, ranging from to 5 1,000, , , , , , , , , , Prevalence, per habitats Statistically significant correlation between the annual cost and the prevalence (p=0.0045)

15 Is cost driven by the severity? T = 0.01 p = (81) 13 (19%) Most of diseases were not classified as severe be the EMA. No significant association between the severity of the disease and the annual cost of treatment.

16 Regression model Negative binomial with outliers Negative binomial without outliers Prevalence NS Age <.0001 <.0001 Alternatives Severity NS ATC code <.0001 <.0001 Treatment line NS Type of study Comparator <.0001 Endpoint NS NS IAB score < Comm. Date <.0001 <.0001 Delay NS p <p 0.2 p>

17 Model results and discussion Prevalence Age Alternatives Severity ATC code Treatment line Type of study Comparator Endpoint IAB score NS Lower cost in elderly patients Impact (if significant) Higher cost for No or One alternatives NS Highest costs in A (Alimentary tract and metabolism) and H (Systemic hormonal preparations) classes Higher cost for First line Higher cost for Phase III Higher costs for active comparator NS Higher costs for IAB I-II Comm. Date Lower costs in , higher costs in Delay Inverse ratio

18 Discussion The rarity by itself seems not to be valued by payers. The quality of submitted evidence has an impact on drug costs. There is a complex association between the annual treatment cost and the covariates which cannot be explained only by the IAB score. Study limitations: Small number of observations Costs for hospital only drugs not available Complex correlation structure between covariates

19 Thank you Daria Korchagina Paris-Sud University

20 Back up

21 Data extraction Therapeutic area (EPAR) Prevalence (orphan designation) Population age (EPAR) Severity (Orphan designation) Alternative treatments (HTA report) ATC class (EPAR) Treatment line (HTA report) MA date (EPAR) Posology Disease Drug Type of the pilot study (HTA report) Nb of patients in the study (HTA report) Comparator (HTA report) Endpoint (hard vs. surrogate) (HTA report) Evidence AB score IAB score HTA date Commercialisation date (Price lists) Price (ex-factory, retail) (Price lists) Reimbursement level (Price lists) Delay between MA and commercialization HTA

22 Annual cost as categorical variable Q1 Q2 Q3 Q4 Nb of valid values Mean (Sd) (3451) (4645) (8671) (237355) 95% CI [ ; 7 389] [ ; ] [ ; ] [ ; ] Min-Max [ ; ] [ ; ] [ ; ] [ ; ] Median

23 Percentage Annual cost Disease characteristics Prevalence Prevalence Mean 1.23 (1.10) Median % CI [0.97 ; 1.50] Min-Max [0.0 ; 5.0] 1,000, , , , , , , , , ,000 Prevalence, per habitats Prevalence, per habitats Statistically significant correlation between the annual cost and the prevalence (p=0.0045)

24 Disease characteristics Severity T = 0.01 p = (81) 13 (19%) Most of diseases were not classified as severe be the EMA. No significant association between the severity of the disease and the annual cost of treatment.

25 Disease characteristics Therapeutic area T = 3.28 p = (39%) 20 (29%) 1 (1%) 5 (7%) 4 (6%) 6 (9%) 4 1 (1%) 1 (1%) 1 (1%) (6%) I Infectious and parasitic diseases II Neoplasms III Diseases of the blood and blood-forming organs IV Endocrine, nutritional and metabolic diseases VI Diseases of the nervous system IX Diseases of the circulatory system X Diseases of the respiratory system XI Diseases of the digestive system XIX Injury, poisoning and certain other consequences of external causes NC Not classified Most of molecules target oncology and metabolic diseases. Significantly higher costs for the treatment of metabolic diseases.

26 Disease characteristics Age of targeted population W = 2.84 p = (50%) 15 (21%) 14 (20%) 6 (9%) Most of molecules are indicated in adult patients. No significant association between the age of targeted population and the cost.

27 Disease characteristics Alternative treatment T = 3.18 p = (44%) 22 (32%) 10 (14%) 7 (10%) Several treatment options exist for the most of diseases. Significant association between the number of alternative treatments and the cost.

28 Drug characteristics Treatment line W = 1.87 p = (60%) 28 (40%) Most of OD are to be used in the first line. No significant association between the treatment line and the cost

29 Drug characteristics ATC class W = p = (47%) 5 (7%) 14 (20%) 3 (4%) 5 (7%) 2 (3%) 3 (4%) 3 (4%) 1 (1%) 1 (1%) L Antineoplastic and immunomodulating agents C Cardiovascular system A Alimentary tract and metabolism J Antiinfectives for systemic use N Nervous system V Various H Systemic hormonal preparations, excluding sex hormones and insulins R Antiparasitic products, insecticides and repellents G Genito-urinary system and sex hormones B Blood and blood forming organs Most of molecules are from immunomodulating agents or alimentary tract and metabolism classes. Significant association between ATC class and the cost

30 Submitted evidence Type of study T = 0.8 p = (64%) 14 (20%) 11 (16%) Most of molecules were tested in a Phase III clinical trial. No significant association between the type of submitted study the cost

31 Submitted evidence Type of comparator T = 0.77 p = (42%) 20 (30%) 19 (28%) Most of molecules were tested vs. Placebo. No significant association between the type of comparator and the cost

32 Submitted evidence Endpoint T = 0.39 p = (80%) 12 (20%) The efficacy of most of ODs was evaluated using a surrogate endpoint. No significant association between the type of endpoint and the cost

33 Frequency Annual cost, HTA IAB score T = 1.43 p = (38%) 6 (9%) 14 (21%) 15 (22%) 7 (10%) IAB score IAB score Most of ODs were assigned IAB II by the HAS. No significant association between the IAB score and the cost

34 HTA Delay between HTA and commercialization Prevalence Nb of valid values 70 Mean (Sd) 6.64 (10.31) 95% CI [4.19 ; 9.10] Min-Max [1.0 ; 67.0] Median 1.0 Pearson p= Spearman p=

35 HTA Date of commercialization T = 0.57 p = 0.87 No significant association between the date of commercialisation and the annual cost of treatment

36 Model 1 Negative binomial with outliers Negative binomial without outliers Prevalence NS NS Age NS Alternatives Severity NS NS NS ATC code NS Treatment line NS NS Multinomial logistic Type of study x x x Comparator x x x Endpoint x x x IAB score Comm. Date x x x Delay NS NS NS p <p 0.2 p>

37 Selection of the variables Prevalence Age Alternatives Severity ATC code Treatment line Type of study Comparator Endpoint IAB score Comm. Date Delay p <p 0.2 p>0.2 Continuous Categorical Final decision