Table 3 CDRa comments on recommendations for orphan drugs with high ICURs
Drug | Disease | Recommendation (Date of decision) | ICURb | Patient input | CDR comments |
|---|---|---|---|---|---|
Eculizumab | Paroxysmal nocturnal hemoglobinuria | Do not list at the submitted price (19–02-2010) | $500,000 to $2.4 million/QALY (vs. BSC) | No reference to patient input | Double blind RCT (n = 87 patients) showed a significant reduction in hemolysis and improvement in QoL with eculizumab (versus placebo) but was not designed to assess effect on survival or thrombotic events, a prognostic factor for survival. CDR concluded that the drug was not cost-effective |
Eltrombopag olamine | Chronic immune thrombocytopenic purpura (ITP) | Do not list (24/10/2011) | Confidentialc | No patient groups responded to the CDR call for input | Data from three RCTs (n = 429) was reviewed but only one trial (n = 197) was discussed (others were excluded because of a limited study duration). In the study, the percentage of patients achieving the primary outcome (platelet response) was significantly higher with eltrombopag. However, CDR considered this outcome less clinically relevant than bleeding events and noted that there were no RCTs comparing eltrombopag with individual comparator ITP therapies |
Tolvaptan | Autosomal dominant polycystic kidney disease (ADPKD) | Do not list (24/02/2016) | $244,402/QALY (vs. BSC) | Noted the burden of ADPKD on patients and caregivers and stressed that only tolvaptan has been approved for treatment of ADPKD. Patients expect tolvaptan toprolong their lives and improve QoL but also noted the challenges of using tolvaptan (large daily fluid intake, increased urination, dry mouth and thirst) | One Phase III, RCT (n = 1445) showed that tolvaptan significantly delayed clinical progression. However, CDR was concerned about the importance of these outcomes and the extent to which clinical changes are maintained over a patient’s lifetime and potential safety issues associated with the drug. NICE have recommended tolvaptan for rapidly progressing disease but CDR concluded that at present identifying such patients would create challenges for drug plans to consistently implement and the cost-effectiveness of the drug in these populations could not be evaluated, based on available data |
Revised CADTH Framework released in March 2016 | |||||
Asfotase alfa | Pediatric-onset hypophosphatasia (HPP) | List with criteria and conditionsd (23/03/2016) | $2,698,950/QALY (vs. BSC) | Identified a substantial unmet need in treatment of HPP. Details of the clinical impact of the disease were provided and the particular burden oncaregivers emphasized. Patients and caregivers noted that this is the first therapy approved for HPP and that they would be willing to accept extensive side effects if overall QoL was improved | Two open-labelled Phase II studies (n = 72) and one extension study demonstrated improvement in skeletal development and patients appeared to have a lower rate of mortality compared with the rate of HPP mortality from natural disease history data. Because of the heterogeneous patient population, CDR recommended that drug plans and clinical experts establish case-by-case evaluation criteria for initiation and continuation of therapy. CDR considered asfotase alfa not to be cost-effective at the submitted price |
Elosulfase alfa | Mucopolysaccharidosis IVA | List with criteria and conditionsd (20/05/2016) | $1,720,127/QALY (vs. BSC) | Patients expressed a desire to see disease progression stabilized or slowed. Patients receiving elosulfase alfa reported improvements in endurance and stabilization of condition and did not report any major AEs | One double-blind RCT (n = 177) demonstrated significant improvement in six-minute walk test vs. placebo. However, CDR noted uncertainties regarding relevance and validity of the walk test as an outcome and recommended a manufacturer sponsored international registry to collect clinical data. In addition, CDR recommended that goals of therapy be defined on a case-by-case basis and reassessed after 1 year of therapy. Uncertainty was reported regarding true cost-effectiveness and CDR noted that a price reduction of 97% would be required for the ICUR to approach $100,000/QALY |
Canakinumab | Systemic juvenile idiopathic arthritis (sJIA) | List with criteria and conditionsd (17/06/2016) | $824,000/QALY (vs. BSC) | Inability to perform daily routine activities imparts a severe psychological burden on patients and their caregivers. Patient groups noted that responses to treatment options available can vary significantly | Two RCTs (n = 184) demonstrated that canakinumab improved patient QoL, decreased pain and improved function compared to placebo. There are no direct comparisons of canakinumab to other biologic therapies in sJIA but indirect comparisons suggest that it has similar efficacy. One of the criteria of reimbursement is that treatment be discontinued if there is no improvement after day 15. CDR determined that canakinumab is 10 to 15 times higher in price than other sJIA treatments and a reduction in price of approximately 90% would be required to make it a cost-effective option vs. tocilizumab; condition of reimbursement is that drug price should not exceed drug plan cost of tocilizumab |