The role of the Italian Medicine Agency (AIFA)

Luca Pani, M.D.Director GeneralDG@aifa.gov.it

Padova, 12 November 2013

Public Declaration of transparency/interests*

Note: For this presentation I am not receiving any compensation

*Luca Pani, in accordance with the Conflict of Interest Regulations approved by AIFA Board of Directors (26.01.2012) and published in the Italian Government Official Journal on 20.03.2012 according to 0044 EMA/513078/2010 on the handling of the conflicts of interest for scientific committee members and experts

Interests in pharmaceutical industry NO CurrentlyLast 2 years

More than 2 years but less than 5 years ago

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ago(optional)

Direct interests:

Employment with a company X

Consultancy for a company X

Strategic advisory role for a company X

Financial interests X

Ownership of a patent X

Indirect interests:

Principal investigator X

Investigator X

Individual’s Institution/Organisation receives a grant or other funding

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Key discoveries in the basic science of HCV

Molecular virology has deciphered the viral replication cycle, identified druggable targets and generated tools for compound screening. Structural biology has provided high-resolution structures of key viral drug targets.

New drug targets in HCV

As of May 2013, over 1,600 studies evaluating drugs for the treatment of hepatitis C are listed on the ClinicalTrials.gov website. These trials are investigating a multitude of compounds in different patient populations or subpopulations.

Roman numerals in brackets indicate the current clinical phase of development.

Will we have just one anti-HCV pill?It is unlikely that a ‘one size fits all’ approach will be developed given a broad choice of different drugs and a large number of patient characteristics that have an impact on response to treatment. However it seems feasible that many treatment regimens will contain a nucleoside or nucleotide NS5B polymerase inhibitor together with other DAAs, PEG-IFN and/or ribavirin. This presumably will come in the form of a single-pill fixed-dose combination.

AIFA Monitoring Registries for BOC & TVR

AIFA's contribution to existing therapies

AIFA, in collaboration with the University of Padova, designed an electronic web-based algorithm (255 nodes) that identifies the best pharmaceutical pathways to treat HCV. The algorithm is published on the AIFA's portal. http://www.agenziafarmaco.gov.it/it/content/algoritmi-terapeutici

Upcoming medicinal products for Hepatitis C

SimeprevirApplied indication: Simeprevir (SIM) is indicated for the treatment of chronic hepatitis C (CHC) genotype 1 or genotype 4 infection, in combination with peginterferon alfa and ribavirin, in adults with compensated liver disease (including cirrhosis) with or without human immunodeficiency virus-1 (HIV-1) co-infection who are treatment-naïve or who have failed previous interferon therapy (pegylated or non-pegylated) with or without ribavirin.

Mechanism of action: Simeprevir is the third member of direct-acting antiviral agents’ class. It is an inhibitor of the HCV NS3/4A protease and is being developed for the treatment of chronic HCV infection.

Procedure: centralised.

Main efficacy studies: QUEST-1, QUEST-2, PROMISE.

SofosbuvirApplied indication: Sofosbuvir (SOF) is indicated in combination with other agents for the treatment of chronic hepatitis C (CHC) in adults.

Mechanism of action: Sofosbuvir is a novel nucleotide prodrug inhibitor. In human hepatocytes, it is converted to an active uridine triphosphate form which acts as an inhibitor of the HCV NS5B polymerase.

Procedure: accelerated.

Main efficacy studies: FISSION, POSITRON, FUSION, NEUTRINO.

Compassionate use of Sofosbuvir

How to cope with uncertainty when deciding on pricing and reimbursement?

What is the cut-off to be considered between therapeutic utility of a new medicine and its major cost?

How can we make difficult decisions in the absence of ideal information?

What about novel therapies for Hepatitis C?A Regulator’s Challenge

To support regulatory and administrative activities in the achievement of both efficiency

and efficacy

To increase scientific

knowledge on real-world setting

for obtaining relevant data to take strategic

measures

AIFA’s Keywords: Innovation and Sustainability

AIFAhas

developed some useful tools able:

Since 2000 the Italian Health System is one of the first NHS where conditional reimbursement agreements have

been introduced

MEAs classification

Managed entry agreements for pharmaceuticals:The European experience. April 2013.

The Italian context:not only risk to benefit but also benefit to

price

Managed entry agreements for pharmaceuticals:The European experience. April 2013.

Reimbursement (without

conditions)Refusal

Outcome based MEAs

Monitoring registers

AIFA notes

Therapeutic plans

Payment by results

Risk sharing

Oncologicals

Antidiabetics

Psoriasis

Orphans

Cardiovascular

Antireumatics

Volume agreemen

ts

Managing uncertainty relating to clinical benefit and cost-

effectiveness

Managing budget impact

Managing utilisation to optimize

performance

Non-Outcome based MEAs

Cost sharing

Budget cap

What are the AIFA's priorities? Supporting the prescription appropriateness and NHS

sustainability considering the clinical evidence reported in the national and international guidelines and real life data.

Models of MEAs in ItalyThree different ways to share responsibility and risk between pharmaceuticals companies and NHS (third payer).1.Cost Sharing, discount on price of initial therapy cycle(s) for all eligible patients 2.Risk Sharing, discount on price of initial therapy cycle(s) for non-responder3.Payment by Results, initial cycle(s) fully reimbursed by marketing authorization holder for non-responder (fully reimbursed by NHS for responders)

Risk sharing and Payment by Results are performance based-agreements conditioned on clinical evaluation of specific endpoints, with limitations of cost if the effect is inappropriate. The agreement is for a limited period of time, under specific conditions, and to be re-evaluated.

Registries as Administrative & Research Tools

Biomedical research on disease and drug development

Drug Access for patient and clinical practice in real life use

Monitoring registries

Efficacy and safety data collection

Marketing authorization

bedside-to-community

bench-to-bedside

In conclusion: valorization of true innovation

InnovationPathology

Drug

Safety

Efficacy

Cost/Efficacy

AIFA’s new algorithm on innovation

AIFA’s new domains

Innovation must represent a therapeutic advantage

Innovation must be "measurable“ on:

Population selection. Robustness of endpoint(s). Choice of comparators. Duration of therapeutic effect

Innovation should be valued against the National context

Innovation must meet pharmaco-economic studies and HTA standards in order to determine the ratio of incremental cost-effectiveness compared to the standard reference standard

Backup slides: HCV Algorithm

Example of one initial node…

Example of one intermediate node…

Example of one final node…

Example of one initial node…

Example of one intermediate node…

Example of one final node…