Transcript HCV compassionate use programme the French experience

HCV compassionate use programme
The French experience
Daniel Dhumeaux,
Henri Mondor hospital
Créteil, France
[email protected]
Amsterdam, April 27,2013
CUPIC
CUPIC
(Compassionate Use of Protease Inhibitors in viral C Cirrhosis)
- National multicenter observatory in the setting
of ATU * (promoter ANRS)
- Evaluation of real-life safety and efficacy of triple therapy
(including telaprevir or boceprevir associated with
peginterferon plus ribavirin) in HCV genotype 1
patients with compensated cirrhosis who were non
responders to previous dual therapy
*Autorisation temporaire d’utilisation (temporary authorisation for use)
Early access programme
Treatment regimen
Peg-IFN
+ RBV
n=205
BOC + Peg-IFN α-2b + RBV
Follow-up
BOC: 800 mg/8h; Peg-IFNα-2b: 1.5 µg/kg/week; RBV: 800 to 1400 mg/day
TVR + Peg-IFN α-2a +
RBV
n=292
Peg-IFN α-2a + RBV
Follow-up
TVR: 750 mg/8h; Peg-IFNα-2a: 180 µg/week; RBV: 1000 to 1200 mg/day
0
4
8
12
16
36
72
48
Weeks
http://www.afssaps.fr/var/afssaps_site/storage/original/application/4b8c53711bab9d8f7d4c3f947caa90f6.pdf
http://www.afssaps.fr/var/afssaps_site/storage/original/application/fa78af08e029caf9d82bcd9d3e77eb09.pdf
Safety (SVR12)
Telaprevir
Boceprevir
Serious adverse events
(SAE)*
54.2%
51.0%
Premature discontinuation
of treatment due to SAE
21.3%
14.2%
(*) % of patients with at least one event
Risk of occurrence of death or severe complications
Platelets
>100,000/µL
Platelets
≤100,000/µL
Albumin ≥35g/L
3.3%
4.3%
Albumin<35g/L
7.1%
44.1%
Risk of occurrence of death or severe complications
Platelets
>100,000/µL
Platelets
≤100,000/µL
Albumin ≥35g/L
3.3%
4.3%
Albumin<35g/L
7.1%
44.1%
Efficacy (SVR12)
SVR (%)
All patients
100 -
Relapsers
Partial responders
53%
50 -
51%
40%
32%
41%
40%
0Telaprevir
Boceprevir
Fontaine et al. J Hepatol 2013;58(suppl.1):S27
The French ATU system
- Implemented in 1994
- More than 1,000 medicinal products assessed since 1994
- Availability 10 to 12 months before market authorisation
application
- Therapeutic areas
. Oncology-haematology
. Central nervous system diseases
. Metabolic disorders
. Infectious diseases including HIV infection and
and viral hepatitis
Criteria for granting ATU
1. The product is a medicinal product (not a preparation)
2. ATU is given for treatment (not for investigation)
3. There is no market authorisation application
4. The patient cannot be included in a clinical trail
5. The disease is serious and/or rare
6. There is no available alternative therapeutic method
7. Efficacy and safety are presumed and benefit is
expected for the patient
Two types of ATU : nominative and cohort ATU
Nominative ATU
. For one patient, on a name
patient basis
. On the request and
responsibility of the clinician
. ATU for the duration of
treatment
. Usually follow-up of patients
and data collection according
to a protocol for therapeutic use
Cohort ATU
. For a group of patients
. Applied by the company
commitment to submit a
marketing authorisation
. ATU for one-year duration,
renewal possible
. Always follow-up of patients
and data collection according
to a protocol of therapeutic use
The ATU system
Success and limitations
- The ATU system is extremely useful for covering public
health needs :
. it is strongly supported by patients ans physicians
. it is contolled by competent authorities (*)
- The risks are (a) to slow down clinical trials and
marketing authorisation applications, (b) to overestimate
efficacy and to underestimate safety
(*) National agency for medicinal product safety
Short and middle-term perspectives for hepatitis C
early access programme in France
- A nominative ATU was recently implemented for
patients having developed severe liver
disease recurrence post-transplantation
(sofosbuvir plus ribavirin)
- A cohort ATU is in progress for (a) patients waiting liver
transplantation, and (b) patients having developed
severe liver disease recurrence post-transplantation
(sofosbuvir plus ribavirin)
Summary
 Use of first generation PI in real life is a major step forward in
HCV treatment :
– increases SVR in all genotype 1 patients including cirrhotics
– is associated with more frequent SAEs, including death, severe
infections and hepatic decompensation and difficult management of
anemia in cirrhotics
• Patients with albumin <35 g/L and platelets <100,000 /mm3 should not
be treated
• Other patients need closer monitoring
– TVR can be administrated twice daily
– Triple therapy (TVR) for 12 weeks in CC, F0-F3 patients with RVR ?
The compassionate use
of
medicinal products.
An example: the French
ATU system
The ATU system
Success and limits
- The ATU system is extremely useful for covering public
health needs :
. It is strongly supported by patients ans physicians
. It is contolled by competent authorities
- The risks are (a) to slow down clinical trials and
marketing autorisation applications, (b) to overestimate
efficacy and to underestimate safety
- Regarding nominative ATU :
. Too many
. Complex system
. No strong regulatory long term status (no mandatory
marketing authorisation application)