4 Committee discussion
The appraisal committee reviewed the data available on the clinical and cost effectiveness of alirocumab, having considered evidence on the nature of primary hypercholesterolaemia and mixed dyslipidaemia and the value placed on the benefits of alirocumab by people with the condition, those who represent them, and clinical experts. It also took into account the effective use of NHS resources.
4.1 The committee heard from the patient experts about the nature of the condition and their experience with treatment. It heard that people with familial hypercholesterolaemia have a lifetime risk of cardiovascular events and their quality of life is adversely affected by the need to be on treatment throughout their life. The committee noted that some people taking statins for hypercholesterolaemia can experience side effects such as muscle and joint pain that can disrupt daily activities and reduce quality of life. It heard from the clinical and patient experts that although low‑density lipoprotein (LDL) apheresis is an alternative treatment option for people with very severe hypercholesterolaemia, it is not available in all areas and is not a sustainable therapy because it requires lengthy attendance at a clinic every 2 weeks and time to recover from the procedure. The committee concluded that the current treatment options for hypercholesterolaemia or mixed dyslipidaemia may not be sufficient in all cases, and that alternative treatment options are desirable.
4.2 The committee discussed the marketing authorisation for alirocumab and how alirocumab might be used in practice. The committee was aware that alirocumab has a marketing authorisation for use in adults with primary hypercholesterolaemia (heterozygous‑familial and non‑familial) or mixed dyslipidaemia (see section 2.1), and understood that 5 clinical groups of people can be distinguished within the marketing authorisation for treating primary hypercholesterolaemia:
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A primary prevention non‑familial hypercholesterolaemia group.
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A secondary prevention non‑familial group of people with established cardiovascular disease, who have previously had a cardiovascular event (the high‑risk cardiovascular disease [non‑familial] population). This group included people with non‑familial hypercholesterolaemia with a history of:
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acute coronary syndrome (such as myocardial infarction or unstable angina requiring hospitalisation)
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coronary or other arterial revascularisation procedures
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coronary heart disease
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ischaemic stroke
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peripheral arterial disease.
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A subgroup of people from the high‑risk group who have had more than 1 previous cardiovascular event or who have polyvascular disease (referred to as the recurrent events/polyvascular disease [non‑familial] population). This group included people with non‑familial hypercholesterolaemia with recurrent cardiovascular events, or cardiovascular events in more than 1 vascular bed.
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A primary prevention heterozygous‑familial hypercholesterolaemia group (the primary prevention [heterozygous‑familial] population)
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A secondary prevention heterozygous‑familial hypercholesterolaemia group (the secondary prevention [heterozygous‑familial] population). This group included people with heterozygous‑familial hypercholesterolaemia with a history of:
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acute coronary syndrome (such as myocardial infarction or unstable angina requiring hospitalisation)
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coronary or other arterial revascularisation procedures
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coronary heart disease
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ischaemic stroke
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peripheral arterial disease.
The committee considered that these groups broadly corresponded to those defined in the company submission. It noted that the homozygous‑familial hypercholesterolaemia population is not within the marketing authorisation for alirocumab (see section 2.1). It also noted that the company did not present any evidence for people with non‑familial hypercholesterolemia without a history of cardiovascular disease (primary prevention) and therefore, agreed that it could not make recommendations for this population. The committee noted that the 4 groups defined by the company were within the marketing authorisation, and concluded that the company's subgroups were appropriately defined and relevant for its decision‑making.
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4.3 The committee discussed whether alirocumab would be used for treating mixed dyslipidaemia. It noted that although the marketing authorisation and the final scope for alirocumab included people with mixed dyslipidaemia, the company did not present any separate evidence for this population. The committee was aware that people with mixed dyslipidaemia also have higher LDL‑C levels, and heard from the clinical experts that treatment for mixed dyslipidaemia is partly determined by LDL‑C level. The committee was aware that people with heterozygous‑familial hypercholesterolaemia are considered to be at high risk of CVD not only because of the high LDL‑C concentrations, but also because of the lifelong exposure to such concentrations. The committee understood from the clinical experts that although alirocumab was likely to mainly be used for primary hypercholesterolaemia in clinical practice, it may also be used for treating mixed dyslipidaemia when LDL‑C levels remain persistently high.
4.4 The committee considered the current treatment options and comparators for people with hypercholesterolaemia. The committee heard from the clinical experts that a maximally tolerated dose of statins is the main treatment option for familial and non‑familial hypercholesterolaemia (as described in NICE's guidelines on familial hypercholesterolaemia and lipid modification), but that a minority of people cannot have statins. It understood that common side effects such as fibromyalgia and headache contribute to intolerance and discontinuation of statin therapy. The committee was also aware that NICE's technology appraisal guidance on ezetimibe for the treatment of primary (heterozygous-familial and non-familial) hypercholesterolaemia recommends ezetimibe monotherapy as an option to treat primary hypercholesterolaemia when statin treatment is insufficient. The committee concluded that a maximally tolerated dose of statins with ezetimibe was the main treatment option and therefore was an appropriate comparator for alirocumab in this appraisal.
4.5 The committee discussed statin therapy for treating hypercholesterolaemia. It was aware that the marketing authorisation stated that alirocumab should be used in combination with a statin or with a statin and other lipid‑lowering therapies in patients unable to reach LDL‑C goals with the maximum tolerated dose of statin, or alone or in combination with other lipid‑lowering therapies in patients who cannot have a statin or for whom a statin is contraindicated (see section 2.1). The committee heard from the clinical expert that although up to approximately 23% of people with primary hypercholesterolemia were currently reported to be intolerant to statins, the true rate was likely to be between 0.5% to 3.0% of the population because there were no clear diagnostic criteria for statin intolerance. The committee acknowledged that there is no universally accepted definition of intolerance to statins, but was aware of the definition of intolerance used in NICE's guideline on familial hypercholesterolaemia. It agreed that some people could be misidentified as intolerant to statins and that the true size of the population that cannot take statins was relatively small compared to the wider population covered by the marketing authorisation. The committee was aware that there may also be people in whom statins are contraindicated. It was aware that these people have the same unmet clinical need as those who cannot tolerate statins and that there is no biologically plausible reason for the alirocumab to work differently in these people. The committee was aware that the populations in the company's new evidence (see section 3.48) were defined by the LDL‑C level at which treatment with alirocumab should be started. The committee was aware that people who cannot take statins have higher than average LDL‑C levels, and would therefore meet the LDL‑C levels needed to start treatment with alirocumab for people who can take statins. The committee concluded that it was not necessary to make separate recommendations for people who cannot take statins.
4.6 The committee discussed the place of lipoprotein apheresis in managing primary hypercholesterolaemia, noting that this was not included as a comparator in the final scope for this appraisal. The committee noted from consultation comments that apheresis is not only costly and onerous for the patient, but also difficult to access because only a few centres offer it. The committee further heard from the clinical expert that lipoprotein apheresis would be considered for people with heterozygous‑familial hypercholesterolaemia whose LDL‑C level remains above 5.0 mmol/l or decreases by less than 40% when taking maximally tolerable doses of combined drug therapy. The committee concluded that treatments that avoid the need for apheresis would be welcomed.
4.7 The committee heard from the clinical expert that alirocumab should only be used when LDL‑C levels are persistently high despite lipid‑lowering therapy. The committee recalled that statins with or without ezetimibe are the main treatment for primary hypercholesterolaemia, but that some people may be misidentified as being unable to take statins (see section 4.5) which may make subsequent treatments less cost effective. Because of this, the committee emphasised that its recommendations for alirocumab should only apply when the maximum tolerated lipid‑lowering therapy has failed. It clarified that this meant that either when the maximum dose has been reached or when further titration is limited by intolerance (as defined in NICE's guideline on familial hypercholesterolaemia: identification and management).
Clinical effectiveness
4.8 The committee considered the clinical‑effectiveness evidence for alirocumab. It agreed that the trials included patients whose characteristics reflected those with hypercholesterolaemia seen in clinical practice in England, and that the results could be generalised to clinical practice. It noted that in people with hypercholesterolaemia, alirocumab statistically significantly reduced LDL‑C levels from baseline at 24 weeks by 39% to 62% compared with placebo, 24% to 36% compared with ezetimibe, and 20% to 49% compared with a statin. The committee heard from the clinical expert that PCSK9 inhibitors could reduce LDL‑C by up to 60% compared with placebo and that the treatment would have a sustained benefit, especially for people with familial hypercholesterolaemia. It also noted the ERG's comments that alirocumab was shown to have a similar safety profile to control groups. The committee concluded that alirocumab is clinically effective in reducing LDL‑C levels when compared with placebo, ezetimibe or statins in people with hypercholesterolaemia.
4.9 The committee discussed the effect of alirocumab on cardiovascular events in people with hypercholesterolaemia. It noted that the trials mainly reported surrogate end points (especially LDL‑C) and were not powered to measure cardiovascular outcomes, which the committee considered to be an important limitation of the evidence base. The committee noted that the company provided information about the relationship between LDL‑C and cardiovascular events from the Navarese meta‑analyses of PCSK9 inhibitor trials. The committee heard from the clinical expert that the currently accepted relationship between LDL‑C and cardiovascular events is based on a Cholesterol Treatment Trialists' Collaboration (CTTC) meta‑analysis of statin trials. It understood that the CTTC meta‑analysis included trials that had long follow‑up periods, were designed to measure cardiovascular outcomes, had a large number of patients and many observed events. In contrast, the Navarese meta‑analysis of PCSK9 inhibitors included trials with shorter follow‑up periods, fewer patients and fewer events. The committee also discussed the company's new evidence submitted in response to the appraisal consultation document, which used the CTTC meta‑analysis. The company stated that although NICE's technology appraisals for ezetimibe and evolocumab used the CTTC meta‑analysis, it had used the most conservative estimate of the relationship between LDL‑C and cardiovascular outcomes in its own modelling for alirocumab. The committee heard from the ERG that this estimate was taken from the most recent update of the CTTC meta‑analysis, which included more trials and patients than the older meta‑analysis used in the other NICE technology appraisals. Therefore, the committee concluded that the most appropriate evidence to assess this relationship was from the most recent update of the CTTC meta‑analysis.
Cost effectiveness
4.10 The committee considered the structure of the company's model. It noted that the model was consistent with the approaches for hypercholesterolaemia developed for related NICE guidance. Although the structure omitted the transient ischaemic attack and stable angina health states, the ERG considered these limitations to be conservative assumptions and considered the model to be of good quality with an appropriate structure. The committee concluded that the company's approach to modelling and the model structure was a reasonable basis for its decision‑making.
4.11 The committee considered the baseline characteristics, risks and the transition probabilities used by the company. The committee understood that they were based on relevant real‑world data from the Health Improvement Network (THIN) database, and noted the ERG's comment that there was good agreement with medium‑term survival for the high‑risk cardiovascular disease and recurrent events/polyvascular disease (non‑familial) populations. The committee therefore agreed that using data from THIN for these populations was appropriate. It understood that the company checked the face validity of baseline characteristics with known prevalence. It was aware that the company acknowledged that the baseline characteristics based on THIN were different from the known prevalence for the primary and secondary prevention (heterozygous‑familial) populations. Therefore, the committee accepted the company's approach using the Dutch lipid criteria with THIN instead of THIN alone, to identify people for the primary prevention (heterozygous‑familial) population because the baseline characteristics were considered more realistic. The committee noted the company's belief that the patient characteristics for the secondary prevention (heterozygous‑familial) population using the Dutch lipid criteria with THIN still lacked face validity, because they were different from known prevalence. The committee noted that the company used an alternative source (Mohrschladt) for this population and that this resulted in a composite annual baseline cardiovascular risk twice as high when compared with data from THIN. Although the ERG was unable to verify whether this alternative source was appropriate, the committee agreed that on balance, given that the patient characteristics from a real‑world dataset (THIN) were different from known prevalence, it was appropriate to use Mohrschladt for the secondary prevention (heterozygous‑familial) population. The committee concluded that the baseline characteristics, risks and transition probabilities used in the company's model were acceptable for its decision‑making.
4.12 The committee considered the incremental cost‑effectiveness ratios (ICERs) per quality‑adjusted life year (QALY) for each group separately (as defined in section 4.2). It considered the ICERs from the company's new evidence in response to the appraisal consultation document, and noted that they incorporated both a revised patient access scheme and the committee's preferred assumptions as outlined in the appraisal consultation document.
4.13 The committee discussed how the company defined subgroups by LDL‑C level for each population in its new evidence. The committee recognised that using subgroups based on LDL‑C levels at which treatment should be started (that is, threshold LDL‑C levels) was consistent with both suggestions from consultation comments received in response to the appraisal consultation document and the committee's approach in previous technology appraisals. However, the committee recognised that the threshold LDL‑C levels were calculated as an average and would therefore include some people in whom alirocumab was most beneficial and cost effective (that is, people at relatively high baseline LDL‑C levels) as well as people in whom alirocumab was less beneficial and cost effective (that is people, at relatively low baseline LDL‑C levels). Therefore, the committee agreed that the LDL‑C levels in the company's new evidence may not be representative of the threshold at which alirocumab would be cost effective for all patients in the subgroup. The committee then noted that the ERG's revised exploratory analysis identified the LDL‑C level at which the ICER could be within the range normally considered to be a cost‑effective use of NHS resources (using a maximum acceptable ICER of less than £30,000 per QALY gained). The committee concluded that the company's approach was clinically plausible and consistent with other NICE technology appraisals for hypercholesterolaemia, and that the ERG's revised exploratory analysis could be used to more accurately identify the LDL‑C level at which the ICER would be within the range normally considered to be a cost‑effective use of NHS resources.
Non‑familial hypercholesterolaemia (primary prevention) population
4.14 The committee noted that the company did not submit evidence for people with non‑familial hypercholesterolaemia without a history of cardiovascular disease (see section 4.2). Because of this, the committee concluded that alirocumab in combination with other lipid‑lowering therapies had not been shown to be a cost‑effective use of NHS resources for treating non‑familial hypercholesterolaemia in adults without a history of cardiovascular disease and did not recommend alirocumab for this group.
Non‑familial hypercholesterolaemia high‑risk cardiovascular disease (secondary prevention) population
4.15 In this population, the ICERs to be considered for alirocumab and a statin plus ezetimibe compared with a statin and ezetimibe were between £24,800 and £44,300 per QALY gained. Applying the ERG's revised exploratory analysis showed that the ICER for alirocumab in combination with other lipid‑lowering therapies compared with other lipid‑lowering therapies alone would be below £30,000 per QALY gained at an LDL‑C level of 4.1 mmol/l. The committee agreed that alirocumab in combination with other lipid‑lowering therapies could be considered a cost‑effective use of NHS resources compared with lipid‑lowering therapies alone for treating primary non‑familial hypercholesterolaemia in adults with a high risk of cardiovascular disease and persistent LDL‑C levels of at least 4.0 mmol/l despite having the maximum tolerated lipid‑lowering therapy, and recommended it for this group.
Non‑familial hypercholesterolaemia recurrent events/polyvascular disease (secondary prevention) population
4.16 In this population, the ICERs to be considered for alirocumab and a statin plus ezetimibe compared with a statin and ezetimibe were between £19,300 and £34,000 per QALY gained. Applying the ERG's revised exploratory analysis showed that the ICER would be below £30,000 per QALY gained at an LDL‑C level of 3.5 mmol/l. The committee agreed that alirocumab in combination with other lipid‑lowering therapies could be considered a cost‑effective use of NHS resources compared with lipid‑lowering therapies alone for treating primary non‑familial hypercholesterolaemia in adults with a very high risk of cardiovascular disease and persistent LDL‑C levels of at least 3.5 mmol/l despite having the maximum tolerated lipid‑lowering therapy, and recommended it for this group.
Heterozygous‑familial hypercholesterolaemia (primary prevention)
4.17 In this population, the ICERs to be considered for alirocumab and a statin plus ezetimibe compared with a statin and ezetimibe were between £37,000 and £50,000 per QALY gained. The committee noted that all of these ICERs were above the maximum acceptable ICER normally considered to represent a cost‑effective use of NHS resources (£20,000 to 30,000 per QALY gained). Although no ICERs were available for LDL‑C levels above 4 mmol/l, the committee noted that, in general, the ICERs tended to decrease as the LDL‑C level threshold for treatment increased. Therefore, it agreed that at higher LDL‑C levels (above 4 mmol/l) the ICER for alirocumab could plausibly approach the range normally considered to be a cost‑effective use of NHS resources. The committee also recalled that the ICERs for specific LDL‑C level thresholds for treatment could include a cohort of people in whom alirocumab would not be cost effective (see section 4.13). The committee noted that the ERG's revised exploratory analysis showed the ICER would be below £30,000 per QALY gained at an LDL‑C level of 6.1 mmol/l, and agreed that this was most likely the LDL‑C level at which the ICER would be within the range normally considered to be a cost‑effective use of NHS resources. The committee also noted that people with hypercholesterolaemia with an LDL‑C level above 5.0 mmol/l would be eligible for apheresis; it recalled its conclusion that treatments that avoid the need for apheresis would be welcomed (see section 4.6), but was aware that the company's model did not incorporate the cost and disutility associated with apheresis, which could reduce the resulting ICER. The committee concluded that despite the high ICERs, alirocumab in combination with other lipid‑lowering therapies could plausibly be considered a cost‑effective use of NHS resources compared with other lipid‑lowering therapies alone for treating heterozygous‑familial hypercholesterolaemia in adults without a history of cardiovascular disease and persistent LDL‑C levels of at least 5.0 mmol/l despite having the maximum tolerated lipid‑lowering therapy, and recommended it for this group.
Heterozygous‑familial hypercholesterolaemia (secondary prevention)
4.18 In this population, the ICERs to be considered for alirocumab and a statin plus ezetimibe compared with a statin and ezetimibe were between £20,000 and £24,000 per QALY gained. Applying the ERG's revised exploratory analysis showed that the ICER for alirocumab in combination with other lipid‑lowering therapies compared with other lipid‑lowering therapies alone would be below £30,000 per QALY gained at an LDL‑C level of 4.0 mmol/l. The committee considered consultation comments that indicated that people with heterozygous‑familial hypercholesterolaemia with a history of cardiovascular disease had a lifelong risk of future cardiovascular events. It also noted consultation comments suggesting that treatment with alirocumab should be started at an LDL‑C level of 3 mmol/l, or at 4.0 mmol/l pending further evidence from cardiovascular outcome studies. The committee accepted that alirocumab would be beneficial for people with a lifelong risk of cardiovascular events in this population group. The committee also considered consultation comments suggesting that an LDL‑C level above 4 mmol/l to start treatment would exclude some people at high risk of cardiovascular disease. Having accepted that a minimum LDL‑C level of 4 mmol/l may exclude a small group of people, the committee agreed that a lower LDL‑C level of 3.5 mmol/l for starting treatment would be more appropriate than 4.0 mmol/l. On balance, the committee concluded that alirocumab in combination with other lipid‑lowering therapies could be considered a cost‑effective use of NHS resources compared with other lipid‑lowering therapies for treating heterozygous‑familial hypercholesterolaemia in adults with a history of cardiovascular disease and persistent LDL‑C levels of at least 3.5 mmol/l despite having the maximum tolerated lipid‑lowering therapy, and recommended it for this group.
Mixed dyslipidaemia
4.19 The committee was aware that the company's model did not include people with mixed dyslipidaemia. It discussed whether its recommendations for primary hypercholesterolaemia could be generalised to mixed dyslipidaemia. The committee recalled that people with mixed dyslipidaemia also have elevated LDL‑C concentrations, and that treatment for mixed dyslipidaemia is partly determined by the LDL‑C concentration (see section 4.3). The committee understood that unlike people with non‑familial hypercholesterolemia, people with heterozygous‑familial hypercholesterolaemia are at high risk of cardiovascular disease not only because of the high LDL‑C concentrations, but also because of the lifelong exposure to such concentrations. Therefore, the committee concluded that the recommendations for people with mixed dyslipidaemia should be the same as the recommendations for people with non‑familial hypercholesterolaemia.
4.20 The committee discussed whether the ICERs presented accurately reflect the cost of alirocumab to the NHS. It understood that the actual discount received by the NHS may be less than the percentage discount offered in the patient access scheme. This is because people may move from secondary to primary care after several years, and simple discounts do not apply when drugs are prescribed through GP's FP10 prescriptions. The committee considered that the subgroups for which alirocumab is recommended have severe hypercholesterolaemia and a high risk of CVD, so treatment should continue in secondary care where simple patient access schemes apply. The committee concluded that the discounted patient access scheme price of alirocumab would be consistently applied for all people for whom alirocumab is recommended.
4.21 The committee discussed whether alirocumab could be considered innovative, and noted that clinical and patient experts thought it to be an innovative drug. The committee acknowledged that alirocumab was one of the first in a new class of drugs with a novel mechanism of action. Even so, it concluded that there was no evidence of additional gains in health‑related quality of life over those already included in the QALY calculations, and that there was no need to change its conclusions on that basis.
4.22 The committee considered a potential equality issue raised by a patient and professional organisation that the incidence of familial hypercholesterolaemia could be higher in people of Ashkenazi Jewish origin. The committee concluded that its recommendations for alirocumab would apply to all patients and that the recommendation would not affect people protected by the equality legislation any differently.
4.23 The committee was aware of NICE's position statement on the Pharmaceutical Price Regulation Scheme (PPRS) 2014, and in particular the PPRS payment mechanism. It accepted the conclusion 'that the 2014 PPRS payment mechanism should not, as a matter of course, be regarded as a relevant consideration in its assessment of the cost effectiveness of branded medicines'. The committee heard nothing to suggest that there is any basis for taking a different view about the relevance of the PPRS to this appraisal. It therefore concluded that the PPRS payment mechanism was not relevant in considering the cost effectiveness of the technology in this appraisal.
Summary of appraisal committee's key conclusions
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TA393 |
Appraisal title: alirocumab for treating primary hypercholesterolaemia and mixed dyslipidaemia |
Section |
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Key conclusion |
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Alirocumab is recommended as an option for treating primary hypercholesterolaemia or mixed dyslipidaemia, only if:
In summary, alirocumab in combination with other lipid‑lowering therapies:
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1.1, 4.14 to 4.18 |
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Current practice |
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Clinical need of patients, including the availability of alternative treatments |
The committee concluded that the current treatment options for hypercholesterolaemia may not be sufficient in all cases, and that alternative treatment options are desirable. |
4.1 |
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The technology |
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Proposed benefits of the technology How innovative is the technology in its potential to make a significant and substantial impact on health‑related benefits? |
The committee acknowledged that alirocumab was one of the first in a new class of drugs with a novel mechanism of action. The committee concluded that alirocumab is clinically effective in reducing LDL‑C levels when compared with placebo, ezetimibe or statins in people with hypercholesterolaemia. There was no evidence of additional gains in health‑related quality of life over those already included in the quality‑of‑life (QALY) calculations. |
4.8, 4.21 |
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What is the position of the treatment in the pathway of care for the condition? |
The committee concluded that a maximally tolerated dose of statins with ezetimibe was the main treatment option and appropriate comparator for hypercholesterolaemia (heterozygous‑familial and non‑familial). |
4.4 |
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Adverse reactions |
The committee noted that alirocumab was shown to have a similar safety profile to control groups. |
4.8 |
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Evidence for clinical effectiveness |
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Availability, nature and quality of evidence |
The committee noted that the trials mainly reported surrogate end points (especially LDL‑C) and were not powered to measure cardiovascular outcomes. |
4.9 |
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Relevance to general clinical practice in the NHS |
The committee concluded that the current treatment options for hypercholesterolaemia may not be sufficient in all cases, and that alternative treatment options are desirable. |
4.1 |
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Uncertainties generated by the evidence |
The committee noted that the trials mainly reported surrogate end points (especially LDL‑C) and were not powered to measure cardiovascular outcomes, which the committee considered to be an important limitation of the evidence base. |
4.9 |
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Are there any clinically relevant subgroups for which there is evidence of differential effectiveness? |
The committee heard from the clinical expert that PCSK9 inhibitors could reduce LDL‑C by up to 60% compared with placebo and that the treatment would have a sustained benefit especially for people with familial hypercholesterolaemia. |
4.6 |
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Estimate of the size of the clinical effectiveness including strength of supporting evidence |
The committee noted that in people with hypercholesterolaemia, alirocumab statistically significantly reduced LDL‑C levels from baseline at 24 weeks by 39% to 62% compared with placebo, 24% to 36% compared with ezetimibe, and 20% to 49% compared with a statin. |
4.8 |
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Evidence for cost effectiveness |
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Availability and nature of evidence |
The committee concluded that the company's model was acceptable for its decision‑making. |
4.10 |
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Uncertainties around and plausibility of assumptions and inputs in the economic model |
The committee concluded that the most appropriate evidence to assess this relationship between LDL‑C and cardiovascular outcomes was from the most recent update of the CTTC meta‑analysis. The committee noted that the company incorporated both a revised patient access scheme and the committee's preferred assumptions as outlined in the appraisal consultation document. |
3.48, 4.9 |
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Incorporation of health‑related quality‑of‑life benefits and utility values Have any potential significant and substantial health‑related benefits been identified that were not included in the economic model, and how have they been considered? |
There was no evidence of additional gains in health‑related quality of life over those already included in the QALY calculations. |
4.21 |
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Are there specific groups of people for whom the technology is particularly cost effective? |
The committee accepted that alirocumab would be beneficial for people with a lifelong risk of cardiovascular events in the heterozygous‑familial hypercholesterolaemia (secondary prevention) population. |
4.18 |
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What are the key drivers of cost effectiveness? |
The committee was aware that using different rate ratios for the relationship between LDL‑C levels and cardiovascular outcomes could impact on the cost effectiveness of alirocumab. The committee agreed that the LDL‑C levels in the company's new evidence may not be representative of the threshold at which alirocumab would be cost effective for all patients in the subgroup. |
3.53, 4.13 |
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Most likely cost‑effectiveness estimate (given as an ICER) |
For the non‑familial hypercholesterolaemia (primary prevention) population:
For the non‑familial hypercholesterolaemia high‑risk cardiovascular disease (secondary prevention) population:
For the non‑familial hypercholesterolaemia recurrent events/polyvascular disease (secondary prevention) population:
For the heterozygous‑familial hypercholesterolaemia (primary prevention) population:
For the heterozygous‑familial hypercholesterolaemia (secondary prevention) population:
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4.14 to 4.18 |
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Additional factors taken into account |
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Patient access schemes |
The company has agreed a patient access scheme with the Department of Health. |
2.3 |
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End‑of‑life considerations |
Not applicable. |
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Equalities considerations and social value judgements |
The following potential equality issues were identified during the scoping process:
The potential equality issues identified during the scoping process have been noted by the committee. None of these issues related to protected characteristics, as defined by the Equalities Act, and so were not considered equality issues. The following potential equality issue was identified during the consultation:
The committee concluded that its recommendations for alirocumab would apply to all patients and that the recommendation would not affect people protected by the equality legislation any differently. |
4.22 |
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