Diabetes Management: a Regulatory view

Luca Pani DG@aifa.gov.it

10-11 giugno 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

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Direct interests:

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Diabetes: not only a clinical problem

Type 2 diabetes is the most common metabolic disease in Italy and in developed countries.

It is the sixth leading chronic disease by diffusion with a crude prevalence of about 4.9%.

It is estimated that about 3,500,000 Italians suffer from this pathology.

The WHO estimates that every ten seconds a person diesfor a disease related to diabetes

Incretin-based therapies The new class of Incretin-based

therapies entered the arena, but

their place in therapy remains

difficult to determine because of

limited long-term clinical data on

both effectiveness and safety, and

the high cost of therapy. Both GLP-1 receptor agonists and

inhibitors of DPP-4 produce an

improvement in glycemic control

similar to other second-line

therapies, but show some additional

advantages with respect to weight

gain and overall hypoglycemia.

Incretin-based therapies expenditure

According to the OsMed report January-December 2012 on “The use of medicines in Italy”, the Incretin-based therapies expenditure is significantly increased.

EfficacyIncretin-based therapies have a innovative mechanism of action but they have not demonstrated a better efficacy than therapeutic alternatives, as shown by meta-analysis or clinical studies.

Safety

In the clinical studies were reported ADRs including gastrointestinal symptoms (nausea, vomiting), hypoglycemia, increase of pancreatic enzymes and pancreatitis, rhinitis, nasopharyngitis and kidney damage.

Safety

Safety

Safety

Safety

International recommendations

The main recommendation is to differentiate the target of HbA1c according to the characteristics of the patient (less stringent in the complex/fragile patient) and use the most appropriate hypoglycemic drug.

Inzucchi SE et Al. Management of hyperglycaemia in type 2 diabetes: a patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. Vol 35. June 2012.

International recommendations

Incretin-based therapies have not a better efficacy than therapeutic alternatives with a HbA1c reduction of about 0,5-1%.

Inzucchi SE et Al. Management of hyperglycaemia in type 2 diabetes: a patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. Vol 35. June 2012.

The appropriate use of Incretin-based therapy, in dual or triple therapy, concerns patients with a HbA1c level between 7.5% and 8.5%. In the complex/fragile patient a less stringent HbA1c level can be considered.

RCTs ≠ Real Life Data

Real life data are essential to correctly assess the risk/benefit and benefit/cost ratio

Real life data concernig antidiabetic drugsThe experience of AIFA Monitoring Registry

Data collected by the AIFA Monitoring Registry from February 2008 to April 2012 concerned exenatide, sitagliptin, vildagliptin and, from 2010, saxagliptin and liraglutide. AIFA Monitoring Registry has the objective to monitor appropriateness of use, safety profile and effects on metabolic control.

Clinical and anthropometric baseline data

84,476 cases from the AIFA Antidiabetic Monitoring Registry were analyzed. DPP-4 inhibitors (saxagliptin, vildagliptin and sitagliptin associated or not with metformin) were prescribed in 47,566 cases and GLP-1 analogues were used in 36,910 cases.

Measures of therapeutic effect

• The mean change of HbA1c ranged from -1.02 to -0.80%.

• The proportion of cases never reaching HbA1c ≤7% ranged

from 37.5% to 62.7%.

Total treatment costs and mean cost per patient

The total economic NHS burden of cases selected from the Registry was 83,9 Million €: 42% for DPP-4 inhibitors and 58% for GLP-1 analogues. The daily mean cost per patient related to the drugs monitored in the Registry was around € 3.16.

Antidiabetics Italian NHS expenditure and consumption

(DDD) data (2008-2012)

Real-world clinical practice

AIFA Monitoring Registries have identified “niches” of inappropriate prescription of Incretin-based therapies considering the current national and international scientific evidence.

Incretin-based therapies are a concrete example of the importance of evaluating a drug's efficacy and safety in real-world clinical practice in order to define the correct risk/benefit and benefit/cost profiles.

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 agreement

s

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.

Valorization of 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

There is a need to compare the clinical trials data with the real life data to confirm the value of potential innovation. The AIFA Monitoring Registry provides the scientific community with the elements required to make choices targeted to the real needs of public health.

The therapeutic effect of drugs monitored in the Italian real-world

clinical practice in terms of HbA1c mean reduction are similar to

those recorded during phase 2-3 registration trials but with an high

proportion of patients never reaching the clinical HbA1ctarget

suggesting the need to better characterize the subset of patients in which these treatments are effective.

Data collected through the Registries are being used to evaluate the safety profile of Incretin based therapies which are today under closed scrutiny.

Conclusions