1. STARTVerso 4: High rates of early virologic response in HCV genotype 1/HIV-co-infected patients treated with faldaprevir plus pegIFN and RBV
Douglas Dieterich,1 Vicente Soriano,2 Mark Nelson,3 Jürgen Kurt Rockstroh,4 Keikawus Arastéh,5 Sanjay Bhagani,6 Andrew Talal,7 Cristina Tural,8 Richard Vinisko,9 and Jens Kort 9
1Mount Sinai School of Medicine, New York, NY, USA; 2Hospital Carlos III, Madrid, Spain; 3Chelsea and Westminster Hospital, London, UK; 4University of Bonn, Bonn, Germany; 5EPIMED, Vivantes Auguste-Viktoria Hospital, Berlin, Germany; 6Royal Free Hospital, London, UK; 7State University of New York, Buffalo, NY, USA; 8Hospital Universitari Germans Trias i Pujol, Barcelona, Spain; 9Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA
20th Conference on Retroviruses and Opportunistic Infections, March 3–6, 2013

2. Douglas Dieterich, MD Mount Sinai School of Medicine, New York, USA
Presenter disclosure
Douglas Dieterich, MD Mount Sinai School of Medicine, New York, USA
I have had financial relationships within the last 12 months relevant to my presentation with: Boehringer Ingelheim Pharmaceuticals AND My presentation includes information on faldaprevir, which is an investigational compound and is not yet approved

3. Introduction to faldaprevir
Faldaprevir is a potent and selective inhibitor of the HCV NS3/A4 protease
The pharmacokinetics of FDV allow oral once daily administration
Phase IIb data demonstrated potent antiviral activity against HCV GT-1 for:
Faldaprevir combined with pegIFN/RBV
An IFN-free combination of faldaprevir with BI and RBV
Phase III trials are ongoing for the iFree and iBased faldaprevir clinical development programs
Faldaprevir: Interaction with NS3/4A protease
Green = hydrophobic Blue = mildly polar Purple = H bonding
Llinàs-Brunet M, et al. J Med Chem 2010;53:6466–6476; Lemke CT, et al. J Biol Chem 2011;286:11434–11443; Sulkowski MS, et al. Hepatology 2013 Jan 28 [Epub ahead of print]; Zeuzem S, et al. AASLD Congress November 9–13, 2012 [Abstract No. 232].
GT, genotype; HCV, hepatitis C virus;
IFN, interferon alpha; RBV, ribavirin;
BI , a non-nucleoside inhibitor of HCV RNA polymerase

4. STARTVerso 4: Study design (1)
Phase III open-label, sponsor-blinded study in treatment-naïve and relapser patients with chronic HCV GT-1 and HIV infection
Interim data
Primary endpoint: SVR12
Faldaprevir 240 mg QD + pegIFN/RBV
Faldaprevir 240 mg QD + pegIFN/RBV
pegIFN/RBV
pegIFN/RBV
Randomization 1:1
Faldaprevir 120 mg QD
+ pegIFN/RBV
pegIFN/RBV
Day 1
Week 12
Week 24
Week 48
Patients with HCV RNA below LLoQ, at Week 4, and HCV RNA below LLoQ target not detected at Week 8 (=ETS) will be re-randomized 1:1 at week 24 to stop treatment or continue pegIFN/RBV through week 48
Patients who did not achieve ETS will continue pegIFN/RBV through week 48
LLoQ, lower limit of quantification <25 IU/mL HCV RNA; pegIFN: pegylated interferon alfa-2a 180 µg once weekly; QD, once daily; SVR, sustained virologic response at 12 weeks after end of treatment.; ETS, early treatment success
RBV: ribavirin 1000 or 1200 mg daily dose for body weight <75 kg or ≥75 kg, respectively

5. STARTVerso 4: Study design (2)
HCV GT-1 infection, including compensated cirrhosis
HCV treatment-naive or relapsers
Raltegravir or
maraviroc
based
Darunavir/ritonavir or
atazanavir/ritonavir based
ART regimen
Efavirenz
based
No ART
RANDOMIZED
ALLOCATED
Faldaprevir dosage
120 or 240 mg QD
240 mg QD
120 mg QD
ART, antiretroviral therapy; QD, once daily

6. STARTVerso 4: Patient disposition (Week 12 interim data)
Screened
(N=453)
Screen failure
(N=143)
Allocated/Randomized
(N=153/N=157)
Not treated
(N=2)
Faldaprevir (120 or 240 mg QD) + pegIFN/RBV
(N=308)
HCV treatment-naïve
(N=239)
Relapser
(N=69)
Not available (N=18)
Discontinued (N=45)
15 Due to AE
12 Lack of efficacya
18 Other reasonb
Not available (N=4)
Discontinued (N=7)
3 Due to AE
1 Lack of efficacya
3 Other reasonb
Completed 12 weeks of treatment
(N=176)
Completed 12 weeks of treatment
(N=58)
aIncludes: viral rebound ≥1 log10 HCV RNA from previous undetected level; lack of HCV RNA reduction from baseline by ≥ 2 log10 at Week 12; lack of viral response at Week 24. bIncludes: protocol violation, withdrawal by subject, or other reasons
AE, adverse event; ATZ, atazanavir; DRV, darunavir; EFV, efavirenz; r, ritonavir

7. STARTVerso 4: Baseline characteristics
Treatment-naïve
(N=239)
Relapser
(N=69)
Total
(N=308)
Age, years (mean) 47
Male, n (%)
184 (77)
64 (93) 80
Race, n (%) White
Black or African American Othera
179 (75)
39 (16)
21 (9)
63 (91)
2 (3)
4 (6) 79 13 8
ART, n (%) EFV-based
ATZ/r- or DRV/r-based
Ral-based and otherb
No ART (ARV-naïve), n (%)
67 (28)
60 (25)
105 (44)
7 (3)
17 (25)
7 (10)
41 (59)
84 (27)
67 (22)
146 (47)
11 (4)
Mean baseline CD4+ T cell count, cells/µL
544
549
545
Baseline HCV RNA ≥ IU/mL, n (%)
197 (82)
49 (71)
246 (80)
HCV Genotype-1a, n (%)
55 (80)
239 (78)
Cirrhosis F4 or FibroScan >13 kPa, n (%)
40 (17)
11 (16)
51 (17)
aIncludes Asian, Native Hawaiian or other Pacific Islander, American Indian or Alaska Native, and missing data. bIncludes 1 patient taking maraviroc plus emtricitabine/tenofovir disoproxil fumarate, 1 patient taking emtricitabine/tenofovir disoproxil fumarate only. Ral, raltegravir

8. STARTVerso 4: Interim safety and tolerability
Most frequent AEs in >20% of patients
No. of patients (%)
Nausea
Fatigue
Diarrhea
Headache
Asthenia
113 (37)
102 (33)
83 (27)
71 (23)
68 (22)
Other AEs of interest
Anemia
Neutropenia
Rash
Loss of HIV suppressiona
55 (18)
49 (16)
Most frequent serious AEs (>1 patient)
Pyrexia
Abdominal pain
Gastroenteritis
Vomiting
Dehydration
4 (1)
3 (<1)
2 (<1)
aIncrease of HIV plasma RNA >200 copies/mL on two consecutive measurements from prior <40 copies/mL
Three deaths: dyspnea; hemorrhage, cerebrovascular accident; Drug reaction with eosinophilia and systemic symptoms

9. Early virologic response in HIV/HCV co-infected patients: HCV treatment-naïve
Treatment-naïve <LLoQ
Treatment-naïve <LLoQ TND
Proportion of patients (%)
191/ 239
143/239
206/ 239
195/239
Week 4
Week 12
TND target not detected

10. Early virologic response in HIV/HCV co-infected patients: HCV treatment-naïve and relapsers
Treatment-naïve <LLoQ
Treatment-naïve <LLoQ TND
Relapser <LLoQ
Relapser <LLoQ TND
Proportion of patients (%)
191/ 239
143/239
63/ 69
51/ 69
206/ 239
195/239
64/ 69
63/ 69
Week 4
Week 12

11. Early virologic response in HIV/HCV co-infected patients: comparison with HCV mono-infected patients
Treatment-naïve <LLoQ
Treatment-naïve <LLoQ TND
Mono-infected patients, SILEN-C1 study:
Relapser <LLoQ
Relapser <LLoQ TND
Treatment-naïve <LLoQ TND a a
Proportion of patients (%)
191/ 239
143/239
63/ 69
51/ 69
108/142
206/ 239
195/239
64/ 69
63/ 69
132/142
Week 4
Week 12
aSILEN-C1 study arm of 240mg QD FDV plus pegIFN/RBV in HCV GT1 treatment-naïve monoinfected patients without cirrhosis; data on file

12. Response guided therapy criteria (ETS) in STARTVerso 4
Treatment-naïve
Relapser
ETS criteria: Wk 4 HCV RNA <LLoQ, + Wk 8 <LLOQ, TND a
YES
Proportion of patients (%)
184/ 239
61/ 69
50% Stop treatment at week 24
50% continue with pegIFN/RBV through week 48
aData missing for 4 patients.
ETS, early treatment success

13. Summary and conclusions
AEs were comparable to those with faldaprevir and pegIFN/RBV in HCV mono-infected patients
ETS was observed in 80% of patients
Half of these patients will stop treatment at Week 24
12-week data show high rates of early virologic response to faldaprevir + pegIFN/RBV
Interim data compare well with early response rates in mono-infected patients
Sustained virologic response data will be used to determine the feasibility of response-guided therapy with faldaprevir
Overall reductions in HCV RNA
Treatment-naïve
Relapsers
Week 4 <LLoQ :
Week 12 <LLoQ TND:
80%
82%
91%

14. Acknowledgments
Patients, and study investigators and site staff at 67 study centers:
Boehringer Ingelheim for sponsoring the study and the Boehringer Ingelheim team
The external Data Monitoring Committee
Brazil
Hans Jäger
Josep Mallolas
Chloe Orkin
Marina Nunez
Carlos Eduardo Brandão Mello
Arastéh Keikawus
Juan Antonio Pineda
Alison Uriel
Gerald Pierone
Raymundo Ferreira Filho
Hartwig Klinker
Daniel Podzamczer
United States
Michael Saag
Paulo Ferreira
Jürgen Kurt Rockstroh
Cristina Tural
John Baxter
Michael Somero
Juvencio Furtado
Italy
Jorge Vergas
Maurizio Bonacini
Richard Sterling
Beatriz Grinsztejn
Giacchino Angarano,
Switzerland
Cynthia Brinson
Mark Sulkowski
Jose Madruga
Andrea Antinori
Manuel Battegay
Douglas Dieterich
Andrew Talal
France
Giovanni Di Perri
Enos Bernasconi
Richard Elion
Kristen Marks
Marc Bourliere
Gaetano Filice
Jan Fehr
Jerome Ernst
Laurent Cotte
Francesco Mazzotta
Andri Rauch
Douglas G. Fish
Pierre-Marie Girard
Paola Nasta
United Kingdom
Federico Hinestrosa
Caroline Lascoux-Combe
Massimo Puoti
Kosh Agarwal
Mamta Jain
Marc-Antoine Valantin
Spain
Sanjay Bhagani
Anthony LaMarca
Germany
Francisco Blanco
Martin Fisher
Eric Lawitz
Johannes Bogner
Manuel Crespo,
Ranjababu Kulasegaram
Cheryl McDonald
Christian Hoffmann
Josep Guardiola
Clifford Leen
Karam Mounzer
Patrick Ingiliz
Juan Carlos Lopez
Mark Nelson
Ronald Nahass