This title slide is titled "KAFTRIO : Évaluation HAS." The subtitle specifies the drug as elexacaftor/tezacaftor/ivacaftor and its clinical and economic evaluation by the HAS.

KAFTRIO : Évaluation HAS

elexacaftor/tezacaftor/ivacaftor - Évaluation clinique et économique par la HAS

Source: logo HAS

This agenda slide, titled "Plan de la présentation," outlines the presentation structure. It includes Introduction, Mechanism of Action, Clinical Evaluation (SMR, ASMR, comparators, therapeutic position), Economic Evaluation (model, ICER/QALY, uncertainties, budget impact), Coherence CT/CEESP, and Conclusion.

Plan de la présentation

1. Introduction
2. Mécanisme d'action
3. Évaluation clinique

SMR, ASMR, comparateurs, place thérapeutique.

4. Évaluation économique

Modèle, ICER/QALY, incertitudes, impact budgétaire.

5. Cohérence CT/CEESP

Discussion cohérence avis CT et CEESP.

6. Conclusion

Source: Présentation HAS sur KAFTRIO (CT/CEESP)

This section header slide is titled "Introduction." It covers the context and therapeutic needs for cystic fibrosis (mucoviscidose), presents KAFTRIO, and outlines the role of HAS (CT/CEESP).

Introduction

Introduction

Mucoviscidose : contexte et besoin thérapeutique. Présentation de KAFTRIO et rôle de la HAS (CT/CEESP).

KAFTRIO combines three CFTR modulators: elexacaftor/tezacaftor (correctors) and ivacaftor (potentiator). It is approved by EMA and FDA in 2020 for patients aged ≥12 years with ≥1 F508del mutation.

KAFTRIO : Contexte thérapeutique

• Association de trois molécules modulateurs CFTR
• Elexacaftor/tezacaftor (correcteurs) + ivacaftor (potentialisateur)
• Pour patients ≥12 ans avec ≥1 mutation F508del
• Autorisé par EMA et FDA en 2020

The slide depicts the mechanism of action of CFTR modulators: elexacaftor/tezacaftor correct CFTR protein folding, while ivacaftor activates the channel. This triple therapy restores chloride transport and improves lung function (FEV1).

Mécanisme d'action

!Image

• Correction pliage CFTR par elexacaftor/tezacaftor
• Activation canal par ivacaftor
• Amélioration fonction pulmonaire (FEV1)
• Triple thérapie : restauration transport chloride

Source: Wikipedia

This section header slide is titled "Évaluation clinique (CT)". Its subtitle outlines the Transparency Commission's opinions on SMR, ASMR, comparators, and the drug's place in the therapeutic strategy.

Évaluation clinique (CT)

Évaluation clinique (CT)

Avis Commission de la Transparence : SMR, ASMR, comparateurs, place dans la stratégie

The slide presents SMR level I (important) and ASMR level II. It also shows +14% FEV1 improvement versus comparators and -72% reduction in pulmonary exacerbations (HR 0.28).

SMR et ASMR

• I: SMR

important

• II: ASMR

niveau II

• +14%: Amélioration FEV1

vs comparateurs

• -72%: Réduction exacerbations

pulmonaires (HR 0.28) Source: HAS (CT/CEESP)

The slide lists Symdeko (tezacaftor/ivacaftor) and Orkambi (lumacaftor/ivacaftor) as comparators—CFTR modulators for CF patients with ≥1 F508del mutation, referenced by HAS. It positions the treatment as first-line for patients with ≥2 F508del mutations, with HAS recommendations of important SMR in CT and priority CEESP reimbursement.

Comparateurs et place thérapeutique

| Symdeko (tezacaftor/ivacaftor) Orkambi (lumacaftor/ivacaftor) Modulateurs CFTR pour patients CF avec ≥1 mutation F508del, évalués par HAS en référence. | 🔲 En 1re ligne pour patients avec ≥ 2 mutations F508del.

Recommandations HAS (encadré) :

• CT : SMR important.
• Priorité remb. CEESP. |

Source: HAS (CT/CEESP)

This slide serves as the section header for Section 4: Évaluation économique (CEESP). It lists key topics such as cost-effectiveness models, ICER/QALY, uncertainties, and budgetary impact.

Évaluation économique (CEESP)

4

Évaluation économique (CEESP)

Modèle coût-efficacité, ICER/QALY, incertitudes, impact budgétaire.

Source: HAS CEESP

The slide displays an ICER of ~45,000 € per QALY from a Markov model, against a French HAS cost-effectiveness threshold of 50,000 €. The ICER position is below the threshold, indicating a favorable economic profile.

Modèle économique et ICER

• ~45 000 €: ICER/QALY

Modèle de Markov

• 50 000 €: Seuil coût-efficacité

Convention HAS France

• < Seuil: Position ICER

Favorable sur le plan Source: HAS / CEESP

The slide outlines key uncertainties, including limited long-term data and uncertain effectiveness in subgroups. It estimates a budgetary impact of +X million euros per year, adjustable through price negotiations.

Incertitudes et impact budgétaire

• Incertitudes : données à long terme limitées
• Incertitudes : efficacité dans sous-groupes incertaine
• Impact budgétaire : +X M€/an estimé
• Impact modulable par négociations de prix

This slide serves as the section header for Section 11, titled "Cohérence CT et CEESP." Its subtitle highlights an analysis of divergences and convergences between clinically favorable and moderately economic aspects.

Cohérence CT et CEESP

11

Cohérence CT et CEESP

Analyse divergences/convergences : Clinique favorable vs économique modérée

Source: HAS - Évaluation KAFTRIO

Both the CT and CEESP commissions agree on KAFTRIO's clinical efficacy, including significant FEV1 improvement (+10.8%), reduced exacerbations, and quality-of-life gains in F508del patients. They diverge on economic uncertainties, with CT affirming strong SMR and CEESP citing high ICER (>100k€/QALY), unclear effect duration, comparators, and uncompensated budgetary impact.

Discussion de cohérence

The slide concludes with a major therapeutic benefit despite high costs, stresses essential post-approval monitoring, and recommends optimizing therapeutic positioning and real-world data. It features perspectives for continuous improvement and thanks the audience for their attention.

Conclusion et perspectives

<ul><li><strong>Bilan :</strong> Apport majeur malgré coût élevé</li><li><strong>Suivi :</strong> Post-AMM indispensable</li><li><strong>Recommandations :</strong> Optimiser place thérapeutique et données réelles</li></ul><p><em>Merci pour votre attention !</em></p>

Perspectives d'amélioration continue

Source: Évaluation HAS de KAFTRIO (CT et CEESP)