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As part of the National Institute for Health and Care Excellence (NICE) highly specialised technology (HST) evaluation programme, Novartis submitted evidence to support the use of onasemnogene abeparvovec as a treatment option for patients with pre-symptomatic 5q spinal muscular atrophy (SMA) with a bi-allelic mutation in the survival of motor neuron (SMN) 1 gene and up to three copies of the SMN2 gene. The Liverpool Reviews and Implementation Group at the University of Liverpool was commissioned to act as the External Assessment Group (EAG). This article summarises the EAG's review of the evidence submitted by the company and provides an overview of the NICE Evaluation Committee's final decision, published in April 2023. The primary source of evidence for this evaluation was the SPR1NT trial, a single-arm trial including 29 babies. The EAG and committee considered that the SPR1NT trial results suggested that onasemnogene abeparvovec is effective in treating pre-symptomatic SMA; however, long-term efficacy data were unavailable and efficacy in babies aged over 6 weeks remained uncertain. Cost-effectiveness analyses conducted by the company and the EAG (using a discounted price for onasemnogene abeparvovec) explored various assumptions; all analyses generated incremental cost-effectiveness ratios (ICERs) that were less than £100,000 per quality-adjusted life-year (QALY) gained. The committee recommended onasemnogene abeparvovec as an option for treating pre-symptomatic 5q SMA with a bi-allelic mutation in the SMN1 gene and up to three copies of the SMN2 gene in babies aged ≤ 12 months only if the company provides it according to the commercial arrangement (i.e. simple discount patient access scheme)., (© 2023. The Author(s).)

As part of the Single Technology Appraisal (STA) process, the UK National Institute for Health and Care Excellence (NICE) invited Apellis Pharmaceuticals/Sobi to submit evidence for the clinical and cost effectiveness of pegcetacoplan versus eculizumab and pegcetacoplan versus ravulizumab for treating paroxysmal nocturnal haemoglobinuria (PNH) in adults whose anaemia is uncontrolled after treatment with a C5 inhibitor. The Liverpool Reviews and Implementation Group at the University of Liverpool was commissioned as the Evidence Review Group (ERG). The company pursued a low incremental cost-effectiveness ratio (ICER) Fast Track Appraisal (FTA). This was a form of STA processed in a shorter time frame and designed for technologies with company base-case ICER < £10,000 per quality-adjusted life-year (QALY) gained and most plausible ICER < £20,000 per QALY gained. This article summarises the ERG's review of the company's evidence submission, and the NICE Appraisal Committee's (AC's) final decision. The company presented clinical evidence from the PEGASUS trial that assessed the efficacy of pegcetacoplan versus eculizumab. At Week 16, patients in the pegcetacoplan arm had statistically significantly greater change from baseline in haemoglobin levels and a higher rate of transfusion avoidance than patients in the eculizumab arm. Using the PEGASUS trial and Study 302 data (a non-inferiority trial that assessed ravulizumab versus eculizumab), the company conducted an anchored matching-adjusted indirect comparison (MAIC) to indirectly estimate the efficacy of pegcetacoplan versus ravulizumab. The company identified key differences between trial designs and populations that could not be adjusted for using anchored MAIC methods. The company and ERG agreed that the anchored MAIC results were not robust and should not inform decision making. In the absence of robust indirect estimates, the company assumed that ravulizumab had equivalent efficacy to eculizumab in the PEGASUS trial population. Results from the company base-case cost-effectiveness analysis showed that treatment with pegcetacoplan dominated eculizumab and ravulizumab. The ERG considered that the long-term effectiveness of pegcetacoplan was uncertain and ran a scenario assuming that after 1 year the efficacy of pegcetacoplan would be the same as eculizumab; treatment with pegcetacoplan continued to dominate eculizumab and ravulizumab. The AC noted that treatment with pegcetacoplan had lower total costs than treatment with eculizumab or ravulizumab because it is self-administered and reduces the need for blood transfusions. If the assumption that ravulizumab has equivalent efficacy to eculizumab does not hold, then this will affect the estimate of the cost effectiveness of pegcetacoplan versus ravulizumab; however, the AC was satisfied that the assumption was reasonable. The AC recommended pegcetacoplan as an option for the treatment of PNH in adults who have uncontrolled anaemia despite treatment with a stable dose of a C5 inhibitor for ≥ 3 months. Pegcetacoplan was the first technology recommended by NICE via the low ICER FTA process., (© 2023. The Author(s).)

The National Institute for Health and Care Excellence (NICE) provides guidance to improve health and social care in England and Wales. NICE invited Daiichi Sankyo to submit evidence for the use of trastuzumab deruxtecan (T-DXd) for treating human epidermal growth factor 2 (HER2)-positive unresectable or metastatic breast cancer (UBC/MBC) after two or more anti-HER2 therapies, in accordance with NICE's Single Technology Appraisal process. The Liverpool Reviews and Implementation Group, part of the University of Liverpool, was commissioned to act as the Evidence Review Group (ERG). This article summarises the ERG's review of the evidence submitted by the company and provides an overview of the NICE Appraisal Committee's (AC's) final decision made in May 2021. Results from the company's base-case fully incremental analysis showed that, compared with T-DXd, eribulin and vinorelbine were dominated and the incremental cost-effectiveness ratio (ICER) per quality-adjusted life year (QALY) gained versus capecitabine was £47,230. The ERG scenario analyses generated a range of ICERs, with the highest being a scenario relating to a comparison of T-DXd versus capecitabine (£78,142 per QALY gained). The ERG considered that due to a lack of appropriate clinical effectiveness evidence, the relative effectiveness of T-DXd versus any comparator treatment could not be determined with any degree of certainty. The NICE AC agreed that the modelling of overall survival was highly uncertain and concluded that treatment with T-DXd could not be recommended for routine use within the National Health Service (NHS). T-DXd was, however, recommended for use within the Cancer Drugs Fund, provided Managed Access Agreement conditions were followed., (© 2023. The Author(s).)

As part of the Single Technology Appraisal process, the National Institute for Health and Care Excellence (NICE) invited Pierre Fabre to submit evidence for the clinical and cost-effectiveness of encorafenib with binimetinib (Enco + Bini) versus dabrafenib with trametinib (Dab + Tram) as a first-line treatment for advanced (unresectable or metastatic) BRAF V600 mutation-positive melanoma. The Liverpool Reviews and Implementation Group at the University of Liverpool was commissioned as the Evidence Review Group (ERG). This article summarises the ERG's review of the company's evidence submission (CS), and the Appraisal Committee's (AC's) final decision. The main clinical evidence in the CS was derived from the COLUMBUS trial and focused on the efficacy of Enco + Bini (encorafenib 450 mg per day plus binimetinib 45 mg twice daily) compared to vemurafenib. The company conducted network meta-analyses (NMAs) to indirectly estimate the relative effects of progression-free survival (PFS), overall survival (OS), adverse events (AEs) and health-related quality of life (HRQoL) for Enco + Bini versus Dab + Tram. None of the results from the NMAs demonstrated a statistically significant difference between the treatment regimens for any outcomes. The ERG advised caution when interpreting the results from the company's NMAs due to limitations relating to the methods. The ERG considered that use of the OS and PFS hazard ratios (HRs) generated by the company's NMAs to model the relative effectiveness of Enco + Bini versus Dab + Tram in the company model was inappropriate as these estimates were not statistically significantly different. The ERG amended the company's economic model to include estimates of equivalent efficacy, safety and HRQoL for Enco + Bini and Dab + Tram. The ERG considered use of different estimates of relative dose intensity to be inappropriate and used the same estimate for both drug combinations. The ERG also concluded that as only the prices of drug combinations were different, a cost comparison was an appropriate method of economic analysis. Using this approach (combined with confidential discounted drug prices for Enco + Bini and Dab + Tram), treatment with Enco + Bini was more cost effective than treatment with Dab + Tram. The AC raised concerns that an absence of evidence of a difference in outcomes between Enco + Bini and Dab + Tram did not constitute evidence of absence. However, as the numerical differences in outcomes generated by the company's networks were small, the AC did not have a preferred approach and considered that both the company's and the ERG's methods of incorporating outcome estimates into the economic model were suitable for decision making. The NICE AC recommended Enco + Bini as a first-line treatment for unresectable or metastatic melanoma with a BRAF V600 mutation.

As part of the single technology appraisal process, the National Institute for Health and Care Excellence invited Takeda UK Ltd to submit clinical- and cost-effectiveness evidence for brentuximab vedotin (BV) for treating relapsed or refractory CD30-positive (CD30+) cutaneous T-cell lymphoma (CTCL). The Liverpool Reviews and Implementation Group at the University of Liverpool was commissioned to act as the evidence review group (ERG). This article summarises the ERG's review of the company's submission for BV and the appraisal committee (AC) decision. The principal clinical evidence was derived from a subgroup of patients with advanced-stage CD30+ mycosis fungoides (MF) or primary cutaneous anaplastic large-cell lymphoma (pcALCL) in the phase III ALCANZA randomised controlled trial (RCT). This trial compared BV versus physician's choice (PC) of methotrexate or bexarotene. Evidence from three observational studies was also presented, which included patients with other CTCL subtypes. The ERG's main concerns with the clinical evidence were the lack of RCT evidence for CTCL subtypes other than MF or pcALCL, lack of robust overall survival data (data were immature and confounded by subsequent treatment and treatment crossover on disease progression) and lack of conclusive results from analyses of health-related quality-of-life data. The ERG noted that many areas of uncertainty in the cost-effectiveness analysis were related to the clinical data, arising from the rarity of the condition and its subtypes and the complexity of the treatment pathway. The ERG highlighted that the inclusion of allogeneic stem-cell transplant (alloSCT) as an option in the treatment pathway was based on weak evidence and generated more uncertainty in a disease area that, because of its rarity and diversity, was already highly uncertain. The ERG also lacked confidence in the company's modelling of the post-progression pathway and was concerned that it may not produce reliable results. Results from the company's base-case comparison (including a simple discount patient access scheme [PAS] for BV) showed that treatment with BV dominated PC. The ERG's revisions and scenario analyses highlighted the high level of uncertainty around the company base-case cost-effectiveness results, ranging from BV dominating PC to an incremental cost-effectiveness ratio per quality-adjusted life-year gained of £494,981. The AC concluded that it was appropriate to include alloSCT in the treatment pathway even though data were limited. The AC recommended BV as an option for treating CD30+ CTCL after at least one systemic therapy in adults if they have MF, stage IIB or higher pcALCL or Sézary syndrome and if the company provides BV according to the commercial arrangement (i.e. simple discount PAS).

As part of the Single Technology Appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer of cenegermin (OXERVATE ® , Dompé) to submit evidence for the clinical and cost effectiveness of cenegermin for neurotrophic keratitis (NK). The Liverpool Reviews and Implementation Group (LRiG) at the University of Liverpool was commissioned to act as the Evidence Review Group (ERG). This article summarises the ERG's review of the evidence submitted by the company and provides a summary of the Appraisal Committee's (AC) final decision. Clinical-effectiveness evidence from two phase II randomised controlled trials (RCTs) of cenegermin found cenegermin to improve corneal healing after 8 weeks compared with vehicle, considered a proxy for artificial tears. Longer-term data and comparisons with other relevant comparators were insufficient to draw conclusions. The company developed a de novo economic model that found cenegermin to be dominant when compared with artificial tears, except in one of seven scenarios. However, the ERG considered that the model had a major structural flaw in that it failed to allow patients to enter a 'sustained healing' state from 'standard of care (SoC) non-healing' and 'SoC deteriorating' states, or to move into an 'SoC deteriorating' state from an 'SoC non-healing' state. Following the first AC meeting, the company submitted a revised model with a revised model structure that removed the 'SoC deteriorating' state and introduced an 'SoC healed' state to sit alongside the existing 'sustained healing' and 'SoC non-healing' states from the original model. However, the ERG continued to express concerns, which included (1) extrapolation of the treatment effect of cenegermin over a patient's lifetime; (2) the assumption that patients had two specialist visits a month; (3) the assumption that artificial tears, autologous serum eye drops and contact lenses continued for a lifetime after healing; (4) the simplified modelling of costs and utilities; and (5) the underlying uncertainty in the utility values. The ERG therefore considered the company's model could not produce a robust incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY) gained. The ERG did however present an alternative ICER by amending the use and cost of autologous serum eye drops, contact lenses and artificial tears in the 'healed' and 'non-healed' states. Applying these changes produced an ICER of £302,717 per QALY gained. Because of uncertainties with the clinical- and cost-effectiveness evidence, the AC concluded that cenegermin cannot be recommended within its marketing authorisation for NK.

Eribulin is a recommended treatment option for locally advanced or metastatic breast cancer (LABC/MBC) in adults whose disease has progressed after at least two chemotherapy regimens. The National Institute for Health and Care Excellence (NICE) invited the manufacturer of eribulin (Halaven ® ; Eisai Ltd) to submit evidence for the clinical and cost effectiveness of eribulin for treating LABC/MBC after one chemotherapy regimen in accordance with the institute's Single Technology Appraisal (STA) process. This article presents a summary of the company's evidence, Evidence Review Group (ERG) review and resulting NICE guidance (TA515), issued 28 March 2018. Clinical evidence for eribulin versus capecitabine in LABC/MBC was derived from a subgroup of 392 patients with human epidermal growth factor receptor (HER2)-negative disease which had progressed after only one prior chemotherapy regimen for LABC/MBC in the phase III, randomised, controlled Study 301 (n = 1102). Overall survival (OS) but not progression-free survival (PFS) was improved for patients treated with eribulin versus capecitabine in this subgroup. Using the discounted patient access scheme price for eribulin, the company developed a de novo economic model. In the base case, the incremental cost-effectiveness ratio (ICER) for eribulin versus capecitabine was £36,244 per quality-adjusted life year (QALY) gained. However, the ERG identified several problematic issues relating to modelling OS and PFS, drug costing and utility values, and made ten revisions to the company model. The overall impact of all ten revisions was to increase the ICER per QALY gained by £46,499. The Appraisal Committee (AC) accepted all changes made by the ERG except for the change to utility values; the AC considered that the value should be mid-way between the company's and the ERG's preferred values. A modified model was submitted by the company that included this utility value, but maintained some elements of the base case that the AC had been critical of (differential PFS between treatment arms and application of treatment cap). The new model also included a 'blended' comparator (capecitabine and vinorelbine). The AC noted there was no evidence to support a 'blended' comparator, differential PFS between treatment arms or a treatment cap. The AC therefore concluded that the most plausible ICER was likely to be £69,843 per QALY gained (derived from an ERG sensitivity analysis using the AC's preferred utility value, no differential PFS and no treatment cap). Therefore, eribulin was not recommended for treating LABC/MBC in adults who have had only one chemotherapy regimen.