FIDAXOMICIN SLIDE RESOURCE SET FDX/13/0068/EUc | September 2013

Rationale for a new treatment Clostridium difficile infection (CDI) remains a disease for which there are significant unmet needs: –Therapy to provide sustained clinical cure (defined as clinical cure without recurrence) 1 –Therapy to reduce recurrence (relapse and/or reinfection) 1 –Better identification of patients at risk of recurrence or those for whom the impact of recurrence would be most dramatic 2 New approaches under investigation but data from large-scale randomised controlled trials are lacking 3 Management strategies to treat acute episodes of CDI effectively and markedly reduce the risk of recurrence would represent a significant therapeutic advance 4 1.Cornely OA. Clin Microbiol Infect 2012;18(Suppl 6):28­–35; 2.Kelly CP. Clin Microbiol Infect 2012;18(Suppl 6):21­–7; 3.Bauer MP, et al. Clin Microbiol Infect 2009;15:1067–79; 4.Bouza E. Clin Microbiol Infect 2012;18(Suppl 6):5–12. FDX/12/0076/EUk | MB145

Fidaxomicin (DIFICLIR™) chemical structure First in a new class of antibacterials known as macrocycles 1 Fermentation product from Dactylosporangium aurantiacum 1 Unsaturated 18-membered macrocyclic core with two highly functionalised sugars as side chains 2 Main metabolite of fidaxomicin is the hydrolysis product, OP Miller M. Expert Opin Pharmacother 2010;11:1569–78; 2.Swanson RN, et al. Antimicrobial Agents Chemother 1991;35:1108–11; 3.FDA Meeting Briefing Document for Anti-Infective Drugs Advisory Committee, 5 April 2011 (NDA ). Fidaxomicin (C 52 H 74 Cl 2 O 18 ) FDX/12/0076/EUj | OC109

Mechanism of action of fidaxomicin Adapted from Artsimovitch I, et al. Clin Infect Dis 2012;55(Suppl 2):S127–31. Fidaxomicin inhibits bacterial DNA-dependent RNA polymerase –Results in inhibition of the initiation of bacterial RNA synthesis –Causes cell death σ subunit Promoter DNA Active site Closed complex Core RNA polymerase RNA polymerase holoenzyme Second intermediate complex First intermediate complex Open complex Myxopyronin Rifamycins Elongation of mRNA +Nucleotide triphosphates X X X Fidaxomicin FDX/13/0034/EU | ACE03

In vitro activity of fidaxomicin against C. difficile isolates No. isolates tested MIC 50 μg/mLMIC 90 μg/mLMIC range μg/mL 21 1    0.016–  0.12  –    0.001– – –1 1.Credito KL, Appelbaum PC. Antimicrob Agents Chemother 2004;48:4430–4; 2.Finegold SM, et al. Antimicrob Agents Chemother 2004;48:4898–902; 3.Ackermann G, et al. Antimicrob Agents Chemother 2004;48:2280–2; 4.Hecht DW, et al. Antimicrob Agents Chemother 2007;51:2716–19; 5.Karlowsky JA, et al. Antimicrob Agents Chemother 2008;52:4163–5. Fidaxomicin shows good in vitro activity against all strains of C. difficile that have been tested MIC, minimum inhibitory concentration required to inhibit 50%/90% of organisms FDX/12/0076/EUj | OC114

In vitro activity against C. difficile from patients in fidaxomicin trials In vitro activity of fidaxomicin against C. difficile isolates from patients in the phase 2 and 3 clinical trials was consistent with earlier in vitro studies: 1,2 –In the phase 2A proof-of-concept study, the MIC 90 for the 38 C. difficile isolates tested was μg/mL 1 –The activity of fidaxomicin against 792 C. difficile isolates from patients enrolled in the phase 3 trials is shown in the table below 1.Citron DM, et al. Anaerobe 2009;15:234–6; 2.Goldstein EJC, et al. Antimicrob Agents Chemother 2011;55:5194–9. *In pooled analysis of both phase 3 trials No. isolates tested* MIC 50 μg/mLMIC 90 μg/mLMIC range μg/mL –1 MIC, minimum inhibitory concentration required to inhibit 50%/90% of organisms FDX/12/0076/EUj | OC115

Activity against other Gram-positive bacteria Fidaxomicin is not significantly active against Streptococcus spp. –MICs are typically in the range of 16–128 μg/mL 1 Fidaxomicin has MICs in the range of 2–16 μg/mL against Enterococcus spp. –Fidaxomicin is 2–4-fold less active against enterococci than vancomycin (MIC range 0.5–4 μg/mL) 1 –Lower activity of fidaxomicin against enterococci may prove beneficial in reducing colonisation with vancomycin-resistant enterococci (VRE) 2 1.Finegold SM, et al. Antimicrob Agents Chemother 2004;48:4898–902; 2.Nerandzic MN, et al. Abstract presented at ICAAC 2009; K FDX/12/0076/EUj | OC116

Activity against Bacteroides fragilis Louie TJ, et al. Antimicrob Agents Chemother 2009;53:261–3. Colonic levels of B. fragilis before (Day 0) and after treatment (Day 10) CFU, colony-forming units; bid, twice daily; qid, four-times daily; NS, not significant Fidaxomicin 200 mg bid (n=12) Vancomycin 125 mg qid (n=8) p=NS Day 0 Day 10 Day 0 p=0.03 FDX/12/0076/EUj | OC118

Bactericidal effects against C. difficile strains Babakhani F, et al. J Med Microbiol 2011;60:1213–7. Bactericidal activity is defined as a 3 log 10 reduction in CFU CFU, colony-forming units; MIC, minimum inhibitory concentration 1 × × × 10 8 CFU/mL 1 × Control (no drug) Fidaxomicin (4 × MIC; 0.5 µg/mL) Vancomycin (4 × MIC; 4 µg/mL) In vitro activity of fidaxomicin and vancomycin against C. difficile strain ATCC over time Time (hours) FDX/12/0076/EUj | OC119

Post-antibiotic effect Babakhani F, et al. Antimicrob Agents Chemother 2011;55:4427–9. CFU, colony-forming units Recovery of viable C. difficile after 1-hour exposure to fidaxomicin or vancomycin FDX/12/0076/EUj | OC120

Inhibition of C. difficile sporulation Babakhani F, et al. Clin Infect Dis 2012;55(Suppl 2):S162–9. ATCC, American Type Culture Collection; CFU, colony-forming units; MIC, minimum inhibitory concentration Effect of exposure to fidaxomicin or vancomycin on sporulation by C. difficile strain ATCC FDX/12/0076/EUj | OC121

Inhibition of C. difficile toxin production Babakhani F, et al. J Antimicrob Chemother 2013;68:515–22. Toxin levels (% of no-drug control) Effect of exposure to fidaxomicin and vancomycin on toxin levels in C. difficile strain ATCC Data obtained for at least 2 independent runs, on Day 4, following antibiotic addition in vitro; MIC, minimum inhibitory concentration EPG06

Low risk of acquisition of VRE Nerandzic MN, et al. Clin Infect Dis 2012;55(Suppl 2):S121–6. p<0.001 Comparative effects of fidaxomicin and vancomycin on acquisition of VRE 8/114 41/133 VRE, vancomycin-resistant enterococci FDX/12/0076/EUj | OC117

Emergence of resistance to fidaxomicin Low propensity for resistance development 1 Low frequency of spontaneous resistance (FSR) 2 –FSR for fidaxomicin and vancomycin at 8 × MIC: <1.41 × 10 −9 –<4.13 × 10 −9 No MIC shift seen after 12 serial passages 2 No shifts in MIC developed during fidaxomicin therapy in either of the phase 3 trials 2–4 No cross-resistance with existing classes of antibacterial agents 2 1.Babakhani F, et al. Abstract presented at ICAAC 2004; E-2047; 2.FDA Meeting Briefing Document for Anti-Infective Drugs Advisory Committee, 5 April 2011 (NDA ); 3.Louie TJ, et al. N Engl J Med 2011;364:422–31; 4.Cornely OA, et al. Lancet Infect Dis 2012;12:281–9. FDX/12/0076/EUj | OC123

Systemic absorption and pharmacokinetic profile of fidaxomicin and its metabolite (OP-1118) Negligible systemic absorption 1,2 –Plasma levels often below quantifiable limits Plasma concentrations observed within 15 minutes post-dose and detectable for up to 24 hours post-dose 1 Even at the highest doses, no evidence of drug accumulation after multiple dosing for 10 consecutive days 1,2 Maximum plasma concentrations reduced in the fed vs fasted state 3 –Not considered significant because systemic exposure is not relevant to the efficacy of fidaxomicin in CDI 1.FDA Meeting Briefing Document for Anti-Infective Drugs Advisory Committee, 5 April 2011 (NDA ); 2.European Public Assessment Report, 22 September 2011 (EMA/857570/2011); 3.Astellas Pharma Europe Ltd. DIFICLIR (fidaxomicin). Summary of Product Characteristics, 19 December FDX/12/0076/EUj | OC110

Systemic absorption of fidaxomicin and OP-1118 Plasma levels of OP-1118 are ~2-fold higher than parent drug, but still close to quantifiable limits of 5 ng/mL 1 Plasma levels of fidaxomicin and OP-1118 slightly elevated in patients ≥65 years, 1 but still in the low nanogram range and not considered clinically meaningful 2 Peak plasma concentrations 2–6-fold higher in patients with CDI administered fidaxomicin (200 mg bid) for 10 days vs healthy subjects 2 –Varied considerably (several 100-fold) from patient to patient 1 –Mean plasma concentrations still in the nanogram range 1 –No evidence of drug accumulation 1 1.FDA Meeting Briefing Document for Anti-Infective Drugs Advisory Committee, 5 April 2011 (NDA ); 2.Astellas Pharma Europe Ltd. DIFICLIR (fidaxomicin). Summary of Product Characteristics, 19 December bid, twice daily FDX/12/0087/EUu | slide 070

Systemic absorption of fidaxomicin and OP-1118 after multiple dosing in CDI patients FDA Meeting Briefing Document for Anti-Infective Drugs Advisory Committee, 5 April 2011 (NDA ). Mean peak plasma concentrations of fidaxomicin and OP-1118 following oral administration of 200 mg bid to CDI patients for up to 10 consecutive days Mean plasma concentration (range), ng/mL Study 003Study 004 SampleFidaxomicinOP-1118FidaxomicinOP-1118 Day 1 (3–5 hours post-dose) 22.8 (0.4–185) n= (0.3–363) n= (0.4–197) n= (0.5–343) n=153 Day 10 (3–5 hours post-dose) 26.4 (1.9–191) n= (3–370) n= (0.3–187) n= (1.1–871) n=60 bid, twice daily FDX/12/0087/EUu | slide 072

Faecal concentrations of fidaxomicin and OP-1118 Near-complete faecal recovery of parent drug and its metabolite 1 Faecal concentrations of parent drug and metabolite appear to be dose related 1 Faecal concentrations of fidaxomicin are in the microgram to milligram range 1 In patients with CDI, mean faecal concentrations far exceed MIC 90 for C. difficile 2 –No association between faecal concentration and outcome observed Comparison of faecal concentrations of fidaxomicin and OP-1118 in CDI patients in the phase 3 trials showed similar findings to those seen in healthy volunteers 2 –This suggests the gastrointestinal route of elimination is not influenced by the CDI disease process 1.Shue YK, et al. Antimicrob Agents Chemother 2008;52:1391–5; 2.FDA Meeting Briefing Document for Anti-Infective Drugs Advisory Committee, 5 April 2011 (NDA ). FDX/12/0076/EUj | OC111

Faecal concentrations of fidaxomicin and OP-1118 in healthy subjects Shue YK, et al. Antimicrob Agents Chemother 2008;52:1391–5. Near-complete faecal recovery of parent drug and its metabolite Most drug remains in the gastrointestinal tract, the prime site of drug exposure Faecal concentrations of fidaxomicin and OP-1118 following daily oral administration of fidaxomicin 150 mg, 300 mg or 450 mg to healthy volunteers for 10 consecutive days Mean faecal concentration at Day 10 (  SD), μg/g Dose150 mg/day300 mg/day450 mg/day Fidaxomicin823 ± 4361,861 ± 7242,983 ± 1,774 OP ± ± ± 241 FDX/12/0087/EUu | slide 074

Faecal concentrations of fidaxomicin and OP-1118 in patients with CDI FDA Meeting Briefing Document for Anti-Infective Drugs Advisory Committee, 5 April 2011 (NDA ). Faecal concentrations of fidaxomicin and OP-1118 following oral administration of 200 mg bid to CDI patients Mean faecal concentration (range), μg/g Study 003Study 004 SampleFidaxomicinOP-1118FidaxomicinOP-1118 Day 10: Sustained clinical cure 1,298.1 (31.7–4,640) (93.7–4,170) 1,636.2 (182.0–4,790) (142.0–2,440) Day 10: Clinical failure (43.0–1,990) (63.4–1,350) 1,443.6 (5.0–7,630) (99.3–2,290) Mean faecal concentrations exceed the MIC 90 for C. difficile FDX/12/0087/EUu | slide 075

Overview of fidaxomicin drug interactions: cytochrome P450 (CYP) system DrugMetabolic pathwayPotential for interaction WarfarinCYP2C9 substrateNone OmeprazoleCYP2C19 substrateNone MidazolamCYP3A4/5 substrateNone European Public Assessment Report, 22 September 2011 (EMA/857570/2011). No dose adjustment is necessary when fidaxomicin is co-administered with drugs that are CYP substrates FDX/12/0076/EUj | OC112

Overview of fidaxomicin drug interactions: P-glycoprotein (P-gp) system Fidaxomicin and OP-1118 are substrates of P-gp and may be mild-to-moderate inhibitors of intestinal P-gp Fidaxomicin should not be co-administered with drugs that are potent P-gp inhibitors Astellas Pharma Europe Ltd. DIFICLIR (fidaxomicin). Summary of Product Characteristics, 19 December DrugMetabolic pathwayPotential for interaction CyclosporineP-gp inhibitorUnclear DigoxinP-gp substrate Unlikely to be clinically meaningful FDX/12/0076/EUj | OC113

Patient populationRecommendation Older patients (  65 years) No dosage adjustment necessary PaediatricAvoid use; there are no data in this population Renal impairment No dosage adjustment necessary, use with caution in severe renal impairment due to limited clinical data Hepatic impairment No dosage adjustment necessary, use with caution in moderate-to-severe hepatic impairment due to limited clinical data Inflammatory bowel diseaseNo data, use with caution Pseudomembranous colitisLimited data; use with caution PregnantNo data; avoid use Breastfeeding Exposure of drug to newborns/infants via breast milk cannot be excluded. Consider whether to discontinue breastfeeding or to discontinue/abstain from fidaxomicin therapy Use of fidaxomicin in specific patient populations Astellas Pharma Europe Ltd. DIFICLIR (fidaxomicin). Summary of Product Characteristics, 19 December FDX/12/0087/EUu | slide 078

Fidaxomicin (DIFICLIR ™ ) clinical development programme TrialDescriptionFidaxomicinVancomycin Phase 2A 1 Randomised, open- label, dose-ranging study of 10 days’ duration 50 mg bid; 100 mg bid; 200 mg bid (N=48) None Phase 3 (003) 2 North American multicentre, double- blind, randomised, parallel-group study of 10 days’ duration 200 mg bid (N=302) 125 mg qid (N=327) Phase 3 (004) 3 Multinational, multicentre, double- blind, randomised, parallel-group study of 10 days’ duration 200 mg bid (N=270) 125 mg qid (N=265) 1.Louie TJ, et al. Antimicrob Agents Chemother 2009;53:223–8; 2.Louie TJ, et al. N Engl J Med 2011;364:422–31; 3.Cornely OA, et al. Lancet Infect Dis 2012;12:281–9. bid, twice daily; qid, four-times daily FDX/12/0076/EUj | OC124

28-day follow-up Phase 3 registration trials: study design Louie TJ, et al. N Engl J Med 2011;364:422–31; Cornely OA, et al. Lancet Infect Dis 2012;12:281–9. Fidaxomicin 200 mg bid Vancomycin 125 mg qid 10 days of treatment Baseline assessment Assessment at end of treatment Assessment at end of study bid, twice daily; qid, four-times daily FDX/12/0076/EUj | OC125

Phase 3 registration trials: inclusion/exclusion criteria Louie TJ, et al. N Engl J Med 2011;364:422–31; Suppl to: Louie TJ, et al. N Engl J Med 2011;364:422–31; Cornely OA, et al. Lancet Infect Dis 2012;12:281–9; Suppl to: Cornely OA, et al. Lancet Infect Dis 2012;12:281–9; European Public Assessment Report, 22 September 2011 (EMA/857570/2011). *≤4 doses and ≤24 hours of pre-treatment allowed UBM, unformed bowel movement Inclusion criteria Adult (≥16 years) Confirmed diagnosis of CDI: Diarrhoea defined as >3 UBM in a 24-hour period Presence of C. difficile toxins A or B in stool within 48 hours of randomisation Primary episode or first recurrence of CDI Exclusion criteria Life-threatening or fulminant CDI Toxic megacolon Previous exposure to fidaxomicin >1 recurrence or relapse within 3 months Concurrent antibacterial therapy with likely effectiveness in treating CDI such as oral vancomycin,* metronidazole,* bacitracin or fusidic acid Crohn's disease or ulcerative colitis Use of antidiarrhoeal drugs such as loperamide FDX/12/0076/EUj | OC128

Phase 3 registration trials: analysis populations Study populationDefinition Modified intent-to- treat (mITT) Patients with documented CDI who underwent randomisation and received at least one dose of study medication Per protocol (PP) Patients in the mITT population who: –Received at least 3 days’ study medication in the case of treatment failure –Received 8 days’ study medication in the case of clinical cure –Had documented adherence to study protocol –Underwent end of treatment (EOT) evaluation Louie TJ, et al. N Engl J Med 2011;364:422–31; Cornely OA, et al. Lancet Infect Dis 2012;12:281–9. FDX/12/0076/EUj | OC126

Phase 3 registration trials: endpoints Outcome measuresDefinition PRIMARY ENDPOINT Clinical cure Resolution of diarrhoea (≤3 UBM/day for two consecutive days) Maintenance of resolution for the duration of therapy No further requirement for therapy from Day 2 following EOT SECONDARY ENDPOINTS Recurrence Reappearance of >3 diarrhoeal stools per 24-hour period within 30 days of cessation of therapy The presence of C. difficile toxins A or B, or both, in stool The need for re-treatment for CDI Time to resolution of diarrhoea Time elapsing from start of treatment to resolution of diarrhoea (first of two consecutive days of ≤3 UBM that are sustained through EOT) Sustained clinical cure Clinical cure without recurrence during the 30-day follow-up period Louie TJ, et al. N Engl J Med 2011;364:422–31; Cornely OA, et al. Lancet Infect Dis 2012;12:281–9. UBM, unformed bowel movement; EOT, end of treatment FDX/12/0076/EUj | OC127

*Percentages based on patients with typed isolates only (Study 003, n=415; Study 004, n=377); Data from mITT population; SD, standard deviation; UBM, unformed bowel movement; mITT, modified intent to treat Demographic and baseline clinical characteristics Louie TJ, et al. N Engl J Med 2011;364:422–31; Cornely OA, et al. Lancet Infect Dis 2012;12:281–9. Characteristic Study 003Study 004 Fidaxomicin (N=287) Vancomycin (N=309) Fidaxomicin (N=252) Vancomycin (N=257) Mean age (SD), years60.3 (± 16.9)62.9 (± 16.9)64.3 (± 17.9)62.5 (± 18.4) Female (%) Mean number UBM per day (SD)8.1 (± 4.2)8.3 (± 5.4)7.5 (± 4.4)7.5 (± 4.3) Inpatient (%) Previous metronidazole failure (%) Treatment for C. difficile in previous 24 hours (%) Previous episode of CDI (%) BI/NAP1/027 strain* (%) FDX/12/0076/EUj | OC129

Data from mITT population; mITT, modified intent to treat; UBM, unformed bowel movement; WBC, white blood cell Disease severity at baseline European Public Assessment Report, 22 September 2011 (EMA/857570/2011). Baseline disease severity categories defined as: Mild, 4–5 UBM/day or WBC ≤12,000/mm 3 ; Moderate, 6–9 UBM/day or WBC 12,001–15,000 mm 3 ; Severe, ≥10 UBM/day or WBC ≥15,001/mm 3 Baseline disease severity, n % Study 003Study 004 Fidaxomicin (N=287) Vancomycin (N=309) Fidaxomicin (N=252) Vancomycin (N=257) Mild64 (22.3)80 (25.9)77 (30.6)95 (37.0) Moderate111 (38.7)106 (34.3)82 (32.5)73 (28.4) Severe112 (39.0)123 (39.8)90 (35.7)88 (34.2) FDX/12/0076/EUj | OC130

Fidaxomicin pivotal trial results 1.European Public Assessment Report, 22 September 2011 (EMA/857570/2011); 2.Louie TJ, et al. N Engl J Med 2011;364:422–31; 3.Cornely OA, et al. Lancet Infect Dis 2012;12:281– / 287 Subjects achieving endpoint (%) 265/ / / / / / / / / / / Difference (confidence interval) [p value] Study 003 1,2 Study NS, not significant 2.4 (–3.1, 7.8) [p=NS] 10.5 (3.1, 17.7) [p=0.0006] –9.9 (–16.6, –2.9) [p=0.005] –14.2 (–21.4, –6.8) [p=0.0002] 13.2 (5.2, 20.9) [p=0.001] 0.9 (–4.9, 6.7) [p=NS] FDX/12/0076/EUf | EK217

Data from mITT population Time to resolution of diarrhoea Study Study Fidaxomicin (N=287) Vancomycin (N=309) Fidaxomicin (N=252) Vancomycin (N=257) Median time to resolution of diarrhoea, hours Louie TJ, et al. N Engl J Med 2011;364:422–31; 2.Cornely OA, et al. Lancet Infect Dis 2012;12:281–9. No statistically significant differences between treatments with respect to time to resolution of diarrhoea 1,2 FDX/12/0076/EUj | OC134

Fidaxomicin pivotal phase 3 trials: time to recurrence European Public Assessment Report, 22 September 2011 (EMA/857570/2011). Day of follow-up after completion of therapy for CDI Early recurrence (relapse): Fidaxomicin: 7.4% Vancomycin: 19.3% Late recurrence (relapse/reinfection): Fidaxomicin: 7.3% Vancomycin: 8.4% Number of patients with recurrence of CDI 13 p<0.001p=0.560 Vancomycin Fidaxomicin FDX/12/0076/EUr | SJ203

Clinical cure and sustained clinical cure in patients aged ≥65 years Astellas Pharma Europe Ltd. Data on file, FDX/13/0001/EU. 224/264239/283188/264169/283 p=NS NS, not significant Vancomycin Fidaxomicin FDX/13/0034/EU | ACE10

Fidaxomicin – rates of sustained clinical cure in cases of severe CDI European Public Assessment Report, 22 September 2011 (EMA/857570/2011). 95% CI*: 5.2, % CI*: 1.6, 24.2 Vancomycin Fidaxomicin Note: CDI severity was determined using European Society of Clinical Microbiology and Infectious Diseases (ESCMID) criteria – i.e. fever (core body temperature >38.5°C); marked leucocytosis (leucocyte count >15 × 10 9 /L) and rise in serum creatinine (≥1.5 mg/dL); *2-sided 95% CI around the difference (fidaxomicin minus vancomycin) in response rates; CI, confidence interval FDX/13/0017/EUb | VZ117

Effect of concomitant antibiotics on CDI recurrence Mullane KM, et al. Clin Infect Dis 2011;53:440–7. Data from pooled analysis; –CA, without concomitant antibiotics; +CA, with concomitant antibiotics; NS, not significant p<0.001 p=NS p<0.001p=0.048 FDX/12/0076/EUr | SJ233

Recurrence in patients with renal impairment at baseline Mullane KM, et al. Am J Nephrol 2013;38:1–11. –10.2% (–17.2, 3.1) –10.0% (–19.4, –0.6) –11.6% (–24.5, 1.3) –16.9% (–35.9, 2.1) 22/20741/19718/12634/14019/8930/915/3412/38 CI, confidence interval; CrCl, creatinine clearance; NS, not significant; post hoc analysis; Data from pooled analysis Difference (95% confidence interval) [p value] Vancomycin Fidaxomicin EPG01

Rates of CDI recurrence in patients with a prior episode Cornely OA, et al. Clin Infect Dis 2012;55(Suppl 2):S154–61. A priori analysis Data from pooled analysis and collected from 128 patients who had recurrent CDI p=0.045 EPG05

Response to treatment of CDI in patients with and without cancer Cornely OA, et al. J Clin Oncol 2013;31:2493–9. p=NS p<0.001p=0.021p=0.001p=0.003 Data from pooled analysis; NS, not significant; post hoc analysis Vancomycin Fidaxomicin EPG04

Time to resolution of diarrhoea in patients with cancer Cornely OA, et al. J Clin Oncol 2013;31:2493– Proportion of subjects with ≤3 UBM/day Time to resolution of diarrhoea (hours) Fidaxomicin (n=87) Vancomycin (n=96) Log rank p-value = EPG02 UBM, unformed bowel movement; Data from pooled analysis

Time to resolution of diarrhoea in patients with cancer (n=183) Cornely OA, et al. J Clin Oncol 2013;31:2493–9. Post hoc analysis; Data from pooled analysis p=0.045 EPG03

Pooled data from phase 3 trials; AE, adverse event Overview of AEs in phase 3 trials European Public Assessment Report, 22 September 2011 (EMA/857570/2011). Type of event, N (%) Fidaxomicin (N=564) Vancomycin (N=583) Any AE373 (66.1)372 (63.8) Study drug-related AE60 (10.6)65 (11.1) AEs leading to discontinuation of study drug or discontinuation from the study 45 (8.0)49 (8.4) Serious AE145 (25.7)135 (23.2) All-cause mortality36 (6.4)38 (6.5) FDX/12/0076/EUj | OC135