Transcript Slides - View the full AIDS 2016 programme

Overcoming remaining challenges:
implementers perspectives on access to HBV
and HCV diagnostics and treatments
I. Andrieux-Meyer , J. Burry, S. Balkan, A. Mesic, D. Maman,
A.Loarec, D.Donchuk, K. Herboczek, M de Souza.
Médecins Sans Frontières
3rd International HIV/Viral Hepatitis Co-infection Meeting
Sunday,17 July 2016; IAS, Durban, South Africa
MSF operations in 2016
• HCV mono-and HIV co-infection: Cambodia,
India, Pakistan, Uzbekistan (MDRTB), South
Africa Cap Town.( UNITAID / MSF)
• HCV –HIV co-infection: Myanmar, India, Iran,
Mozambique, Kenya (UNITAID /MSF).
• HCV Exploratory missions: Vietnam, India,
Ukraine.
• HBV ( PMTCT, HBV mono care) : Myanmar,
Mozambique, CAR, Ivory Coast, DRC Kivu.
DAA Target product profile for
resource limited settings
• Safe, efficacy >90% even 95% in people with cirrhosis or not,
mono ou co-infected with HIV.
• Pan-genotypic.
• Very good tolerability in people with advanced liver and/or renal
disease.
• No interaction with antiretroviral therapy, anti-TB drugs, including
rifampicin and MDR or XDR TB treatements.
• Or possibility to adapt the dose in case of interaction ( this can
exclude FDC)
• Compatibility in pregnant women, formulations for children and
adolescents
• Compatibility with Oral Substitution Therapy , contraception.
• Preserve a second line option
Profil of DAAS development for RLS
profil
Abbvie
3D
MSD
Grazoprevir
Elbasvir
Gilead
Sofosbuvir
ledipasvir
Gilead
Sofosbuvir
Sofosbuvir
daclatasvir
velpatasvir +/GS 9857
Safety
Ok except
cirrhotics
ok
ok
ok
ok
PanGenotypic
No
1-4
No
1-4-6
No
1-2-4-5-6-
1-2-3-4-5-6
Ok in vitro
1-2-3-4Need data in 5-6
Efficacy TT
naive
ok
ok
60% GT6
Not for GT3
ok
ok
Efficacy TT
experienced
(DAA)
Ok GT1 non
cirrhotic
?
Ok post
PEGIFN or
post SOF
SOF VEL 24
weeks : SVR12
90%°
SOF VEL GS
9857 12 wks:
SVR12 99% ͧ
Ok
Side effects
Attention PI
& cirrhosis
ok
ok
ok
Profil of DAAs development for RLS (2)
Profil
AbbVie 3D
MSD Grazo
Elba
Gilead
SOF LED
Gilead
SOF VEL GS
9857
SOF DAC
Interaction
tuberculosis
Rifampicin CI ͪ
RifampicinCI
?
?
CI rifampicin,
Ok MDR
&XDRTB
Interaction
HIV drugs
boosted
protease
inhibitor CI(
deboost)
Efavirenz CI
Efavirenz CI
bPI CI
/ grazoprevir
No dose
adaptation needed
in patients with
cirrhosis Child B or
C
Tenofovir pb
EFV CI
bPI: ok ͣ for
SOF VEL
DAC & EFV
DAC & ATV/r
Dose
adaptation
needed
Buprenorphi
n
methadone
ok
ok
ok
ok
ok
Dose
adaptation
No : FDC
No: FDC
No FDC
No: FDC
possible
PK till 3 y
PK >45 kg
PK 3-12 y
12-17 y:
SVR12 95%ͥ
Children
Adolescents
PK 12-18 y
weight > 45kg
Overview MSF activities in HCV - all sections
OCA
Manipur
HIV
HCV screening
Ab HCV + (%)
1700
OCA
Yangoon
HIV
6500
OCA
Tashkent
HIV
1000
408
F3/F4
F3/F4
Enrolled patients
153
166
Main Genotype
1, 3
1,3
1,3
TTT initiation
45
20
0
Fibrose criteria
16/22* (72%)
SVR12
Molecules used Sofos, Peg,
Sofos , Riba
Riba ,Ledis
Futur
4589
4500
OCG
OCG
Mozambic Dawei
HIV
HIV
900
OCP
Teheran
Women
3500
Dacla to be soon
available
1598
F3/F4
14
300
OCP
Epicentre
Phnom Penh Mbarara
HIV
247
134 (8%) 480 (8%) 238 (24%) 1107 (24%) 2 (0.04%) 14 (1.5%) 300 (9%)
104
RNA HCV +
OCB
OCB
Karachi
Kibera
Gle pop (IDU++) Gle pop
60
12 (39 not
6700
17 (7%) 4 (0.05%)
on going
done)
F3/F4
No
No
F3/F4
F3/F4
No
408
11 (MDM)
14
71
6
3
1
1
1,3,6
1, 3
1,6
307
11
5
9
6
0
35/45 (78%)
Sofos + Rib
To get Dacla. Start
Scale up
Scale up to September 16
Kachin ?
Awaiting
drugs
Sofos /Ledis
Stop Unitaid
MDM patients
Waiting
Sofos +
Dacla
Sofos , Peg,
Riba
Peg Riba
waiting for
Sofos, Dacla
waiting Dacla To use
Reach target Stop Unitaid
Iranian DAA? screening
Target Men (10000) &
400 ttt
MSF HCV treatments guidelines
• Genotypes 1,3,4,5,6:
– preferred regimen: SOFOSBUVIR /DACLATASVIR,
– alternatives: SOFOSBUVIR RIBAVIRIN, or
SOFOSBUVIR LEDIPASVIR ( except GT3)
– Need to collect data for SOFOSBUVIR
/DACLATASVIR in GT 5 &6
• Genotype 2:
– Preferred regimen: SOFOSBUVIR RIBAVIRIN or
SOFOSBUVIR DACLATASVIR,
– alternative SOFOSBUVIR LEDIPASVIR
DNDi/Pharco: Sofosbuvir
ravidasvir
• Goal: short, pangenotypic, easy to use, high
efficacy, safe, all oral.
• Phase II/III Malaysia Thailand started, n=750.
– Possible partnership with South Africa, Vietnam.
• Price <300 $ per course of 12 weeks
• License territories: include Asia, Latin America,
Eastern Europe.
• Possibility to negotiate a license that covers
Europe from 2018.
Ravidasvir Licenses territories
Courtesy DNDi.
Country
Sofosbuvir
Brazil
2,300
Egypt
290
112.5*
Daclatasvir
Simeprevir
849
1,000
175
25*
241
Ledipasvir/sof
+/-400
Viekiera
Exviera
2D: +/-400
France
15,433
9,617
13,049
17,333
2D:15,659, D:1,119
Germany
19,961
14,899
10,484
24,890
2D:19,037
India
300
193-312*
Printed 92$
Market:61
2228 all inclusive
205$/bottle
6,972
16,667
Ivory coast
Italy
Kenya
500*
15,176
#for these DAAS
*generic/ special
price
** full TT
+/- estimated
450*
Malaysia
18,000
Mongolia
300
Nigeria
550*
Pakistan
330
South Africa
400*/2700
22,000
400
6,100
South Corea
17,000
Spain
14,000
9,166
Switzerland
20,590
12,431
Turkey
12,808
Thailand
1,400
Uganda
500
Ukraine
300
UK
18,517
USA
15,234-28,000
1,128
400*/3500
21,000
11,594
2D:20,215;D:1922
21,988
11,763
2,080
12,977
2D: 15,344, D:1588
12,604-31,500
Global price
for DAAs
June 2015
(and March
2016 for
India, South
Africa, Brazil,
).
85,000**
Note: price
per month in
USD
for Public
Health.
Disponibility of HCV treatments in Africa.Mars 2016. Update MSF-Isabelle Andrieux-MeyerCross sectional survey with key informants
country
Sofosbuvir
Prix/ 28tab
daclatasvir
Sofosbuvir ledipasvir
South Africa
Gilead public 300$
Generics:300-400$
Generics India: 90$
(section 21)
Gilead 400 $ public
Algeria
Generics sofos400 1,138$
Burkina Faso
Gilead 548 $
Cameroon
120,000 CFA= 209$
Egypt
Gilead 290$public
Generics:112.5 $*
Ghana
Gilead 258$
Ivory Coast
Nigeria
Uganda
Generics or Gilead 500$
Kenya
Maroc
Gilead 818$
BMS: 175 $
Generics: 25$**
Gilead 400$
Generics: 150$***
Hetero: 450$
BMS: 175$ (MSF)
Gilead 400$
Pharma5: 312$
Pharma5:soon
Sofosbuvir
• Hetero - signed VL with Gilead, limited to the
territory of the license. 200 $ per bottle.lead-time 46 weks to get to Europe.
• Pharco -no VL signed . Lead-time 1-2 weeks to get to
Europe. WHO PQ.
• Registered in Ukraine, Azerbaijan , Kyrgyzstan
• Filed for registration in Pakistan, Kenya, Myanmar,
Cambodia , Vietnam , Ethiopia , Moldova,
Turkmenistan, Sudan , Belarus, Russia , Lebanon , Georgia,
Kazakhstan
Sofosbuvir `ledipasvir
•
•
•
•
•
•
Not good in genotype 3 patients
Alternative to sof daclatasvir otherwise.
Price around $400 per bottle.
No more registered
Lead time 2 months
No generic identified yet, no generic prequalified.
How do governments in resource limited
settings, and patients, get access to DAAs?
• Champion countries: India, Georgia, Egypt, Pakistan: national
programs
• Mongolia, Ukraine: very good community organisations.
• Elsewhere:
–In hospitals: special import permit
–Patient:
• Buyers’ clubs : James Freeman: www.fixhepc.com
• Name patient import
• Access to Indian pharmacies with a medical
prescription / Indian activist networks.
• In Egypt: tour & treat with Pharco
Access to treatment for HBV is discriminatory
Access to tenofovir or entecavir
• The lowest price for tenofovir is 38 usd ppy ( WHO Global Pricing
Reporting Mechanism 2014)
• Entecavir price could be as low as 36 USD PPY.
• Mono-infected HBV patients do not yet have access to this
price structure because countries may not want or not know
they can procure affordable generics of TDF to non HIV
patients, using the Medicines Patent Pool agreement for TDF
for 112 countries.
• But there is no global financing mechanism in place for HBV,
and the drugs need to be registered in the countries for HBV
mono-infection indication.
Overcoming barriers to HCV & HBV
diagnostics and treatments
• Access to reliable epidemiological data , investigation of the patterns of
transmission.
• Access to reliable and affordable diagnostics (WHO pre-qualified, rapid diagnostic
tests, multi-analytic PCR platforms, Point of Care HCV viral load, core antigen
testing).
• Access to care without discrimination, including women and children, people who
use drugs , key populations.
• Demonstration projects: performance & feasibility at large scale, simplification,
task shifting, training, including screening-prevention-treatment in different
epidemiological contexts.
• Promote free generic competition: either through voluntary or compulsory
licensing; patent oppositions / invalidations, and use of all TRIPS flexibilities.
Goal: diagnostic – HCV cure package< $300 per cure.
• Treatment access is slow, complicated, and still extremely limited in June 2016 in
resource limited settings, with concerns about anti-diversion rules, and long
delays/drug registration and drug orders.
• Access to HBV diagnostics-treatments- and birth dose immunization remain
dramatically restricted. HIV PMTCT= perfect opportunity for viral hepatitis care
integration.
Remerciements
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Key informants: Giten Khwairakpam, Othoman Mellouk, World Hepatitis Alliance Bridie Taylor, Charles
Gore,Laura Ciaffi, Serge Eholié, Abshiro Halake, Fumi Lesi, Ponsiano Ocama, Mark Sonderup,
MSF teams : M. Balasegaram, R. Malpani, C. Perrin, Y. Hu, J. Keenan, S. Shettle, T.Roth, G.Elder, L.
Menghaney, S. Gupka, J.Burry, A. Loarec, M. de Souza, D. Maman, D. Donchuk, K. Herboczek ,A. Mesic,
C.Ferreyra,S. Balkan, M. Berthelot, J. Goiri, C. Jamet, M. Serafini, K.Lavelle, S.Cristofani, L.Molfino,
M.Fernandez, P.Boulle, M.Serafini, MSF Ukraine, MSF India, MSF Myanmar, MSF Iran, MSF Pakistan,
MSF Kenya, MSF Mozambique, MSF Chad/Mali, MSF Uganda.
Liverpool University: A.Hill. Bristol University & LSHTM: P.Vickerman, N.Martin.
UNITAID team: Ph.Duneton, K.Timmermans,Ph.Douste Blazy, S.de Lussigny.
Hôpitaux Universitaires de Genève : A.Calmy, T.Lecomte, V. Pecoul, F.Olearo, O.Tshikung, M.Rougemont.
B. Browers, A. François, S. Yerly, F. Negro, L.Kaiser,
WHO team: G.Hirschall, S. Wiktor, P.Easterbrook, S.Hess, H.Harmanci, A.Ball, H.Souissi, N.Ford, A.Vester,
et le WHO HCV Guidelines Development Group: EA Affonso Araujo, Manal El-Sayed, Ch.Gore,
G.Khwairakpam, K.Lacombe, O.Lesi, DR Nelson, P.Ocama, B.Oidov,J.Rockstroh, T.Swan, LE.Taylor,
E.Thompson, L.Wei,
DNDi team: B.Pecoul, M. Lallemant, G.Diap, JP Paccaud, G.Bilbe, JF Alesandrini, F.Saugnac, JR Kiechel,
J.Lee, F.Simon, J.Brenner, P.Boulet.
FixHep C and J.Freeman
Questions: [email protected]
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1. DIAGNOSTICS
⇢ No out-of-pocket expenditures for TB tests
⇢ Rapid molecular test (i.e. Xpert) is initial diagnostic for all
⇢ Second-line drug susceptibility testing is available
2. MODELS OF CARE
⇢ Treatment initiation: TB at primary level, DRTB at district/below
⇢ Compulsory hospitalisation is not required
⇢ Immediate ART is offered to people living with HIV
3. DRUG REGULATION
⇢ NTP procures quality-assured TB drugs
⇢ Prescriptions are required for all TB drugs (not over-the-counter)
⇢ TB drugs benefit from accelerated registration
4. DS-TB TREATMENT
⇢ Daily fixed-dose combinations is standard of care
⇢ Treatment, including for children, reflect WHO guidance
⇢ TB contacts are screened, children & PLWHA receive IPT
5. DR-TB TREATMENT
⇢ DR-TB treatment reflects WHO guidance
⇢ WHO recommended DR-TB drugs are on national EML
⇢ New drugs are available via import waivers until full registration
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