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Safety of Satralizumab Based on Pooled Data from Phase 3 Studies in Patients with Neuromyelitis Optica Spectrum Disorder (NMOSD)

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Disclosures

• B. Greenberg has received grants from Chugai, MedImmune, Genentech,

MedDay, PCORI, NIH, NMSS, and Guthy Jackson Charitable Foundation for NMO; and received consulting fees from Novartis, Alexion, and EMD

• Serono. He is a board member of the Transverse Myelitis Association.
• J. de Seze has received grants and personal fees from Roche; personal

fees from Chugai; and has served advisory boards in Expert committee for the clinical trial conducted by Chugai

• E. Fox has received honoraria for advisory, consulting, speakers’ bureau,

and/or research support from AbbVie, Biogen, Celgene, Chugai, EMD Serono, Genentech/Roche, MedDay, Novartis, Sanofi Genzyme, and TG Therapeutics.

• A. Saiz has received personal compensation for consulting, serving on a

scientific advisory board, speaking, or other activities with Merck-Serono, Sanofi, Biogen, Roche, TEVA, Novartis, and Bayer-Schering.

• T. Yamamura has served on scientific advisory boards for Biogen, Takeda,

Sumitomo, Novartis, and Chugai; received research grants from Chugai, Biogen, Novartis, Teva, Chiome Bioscience, and Miraca Holdings; he received speaker honoraria from Chugai, Takeda, Biogen, Sumitomo

• B. G. Weinshenker reports consulting fees from Mitsubishi Tanabe, Caladrius

Biosciences, Roivant, and Brainstorm Therapeutics; he was a member of the Data Safety Monitoring Committee for Novartis and participated on the Attack Adjudication Committee for Alexion and MedImmune/Viela Bio. He reports personal fees from Chugai for the submitted work. He has a patent NMO-IgG for diagnosis of neuromyelitis optica with royalties paid to RSR Ltd.; Oxford University; Hospices Civil de Lyon, MVZ Labor PD Dr. Volkmann und Kollegen GbR.

• C. Marcillat, X. Kou and K. Weber are employees of F. Hoffmann-La Roche

Ltd This study was funded by Chugai Pharmaceutical Co. Ltd, Tokyo, Japan. Editorial assistance was provided by ApotheCom, UK.

*Last administration; †Last observation; ‡Relapse adjudicated by CEC; ‖Defined by Wingerchuk et al 2006 criteria; ¶Defined by Wingerchuk et al 2007 criteria with either LETM or ON. OLE median treatment exposure: 48.7 weeks (range 10–98). AQP4-IgG, aquaporin 4 immunoglobulin G; AZA, azathioprine; CCOD, clinical cut-off date; CEC, clinical endpoint committee; CI, confidence interval; IST, immunosuppressants; HR, hazard ratio; LETM, longitudinally extensive transverse myelitis; MMF: mycophenolate mofetil; OCs, oral corticosteroids; OLE, open-label extension; ON, optic neuritis; PDR, protocol-defined relapses; sc, subcutaneous.

• 1. Yamamura T, et al. N Engl J Med 2019;381(22):2114–2124. 2. Traboulsee A, et al. Lancet Neurol 2020;19:402–412.

Satralizumab has been evaluated in two phase 3 studies: SAkuraSky (in combination with baseline IST) and SAkuraStar (monotherapy)

SAkuraSky (Satralizumab + baseline IST) (N=83; 1:1 randomization) SAkuraStar (Satralizumab monotherapy) (N=95; 2:1 randomization)

• Aged from 12–74
• NMO‖ (AQP4-IgG+/-) or NMOSD¶ (AQP4-IgG+) patients
• ≥2 relapses in last 2 years (≥1 relapse in last year)
• Stable treatment with AZA, MMF, and/or OCs

Main inclusion criteria

• Aged from 18–74
• NMO‖ (AQP4-IgG+/-) or NMOSD¶ (AQP4-IgG+) patients
• ≥1 attack in last year

Total number of PDR reaches 26 (CCOD 6th Jun 2018) End of double-blind period Total number of PDR reaches 44, or 1.5 years after the date of randomization of the last patient enrolled (CCOD 12th Oct 2018) CEC-confirmed PDR or clinical relapse requiring rescue therapy Criteria for entry into OLE CEC-confirmed PDR Time to first PDR: 62% reduced risk (HR 0.38 [95% CI, 0.16, 0.88]) Primary endpoint met for both trials Time to first PDR: 55% reduced risk (HR 0.45 [95% CI, 0.23, 0.89]) Double-blind period

Satralizumab 120 mg q4w sc Placebo (+ IST in SAkuraSky) Satralizumab 120 mg q4w sc

Relapse‡

Week 2 4 8 12 16 20 LA* Baseline OLE period LO† 2 4 8 12 LA* Randomization

Administration of satralizumab or placebo

Overall satralizumab period

Duration of exposure to study drug (weeks) is defined as (date of last dose - date of first dose + 1)/7. *The overall satralizumab treatment period includes cumulative data from the DB and the OLE. BL, baseline immunosuppressants; CCOD, clinical cut-off date; OLE, open-label extension; SD, standard deviation. Data on file.

Double-blind period

SAkuraSky (N=83) SAkuraStar (N=95) Pooled (N=178)

Satralizumab + BL (n=41) Placebo + BL (n=42) Satralizumab (n=63) Placebo (n=32) Satralizumab (n=104) Placebo (n=74)

Mean exposure (SD), weeks 94.1 (72.6) 66.0 (61.4) 91.1 (56.4) 61.4 (51.4) 92.3 (63.0) 64.0 (57.0) Median exposure (range), weeks 107.4 (2–224) 32.5 (0–180) 92.3 (0–202) 54.6 (2–216) 93.7 (0–224) 42.6 (0–216)

In the overall satralizumab treatment period for the two studies, 166 patients were exposed to at least one dose of satralizumab

▪ Fewer patients experienced relapses in the satralizumab arms, so the average double-blind exposure was higher with satralizumab than with placebo ▪ Satralizumab exposure was further increased when including data from the OLE, as all patients received satralizumab in the OLE ▪ The first patients are now reaching 5.5 years of satralizumab treatment exposure Overall satralizumab treatment period (up to a CCOD of 7 Jun 19)*

Satralizumab (N=166)

133.3 (74.5) 128.6 (4–276)

*Severe AEs were defined as incapacitating AEs affecting the patient’s ability to work or to perform normal daily activities. †MedDRA system organ class: infections and infestations. AE, adverse event; CI, confidence interval; IST, immunosuppressants; MedDRA, Medical Dictionary for Regulatory Activities; PY, patient-years; URTI, upper respiratory tract infection; UTI, urinary tract infection.

• 1. de Seze J, et al. Poster presented at ECTRIMS 2019, Stockholm, Sweden, 11–13 September 2019. Poster no. P1614. 2. Yamamura T, et al. N Engl J Med 2019;381(22):2114–2124.
• 3. Traboulsee A, et al. Lancet Neurol 2020;19:402–412.

In the two studies, the overall rate of AEs and serious AEs was comparable between the placebo and satralizumab groups in the double-blind period

Satralizumab ± IST (n=104)1 (pooled data) Placebo ± IST (n=74)1 Patients n (%) Events per 100 PY (95% CI) Patients n (%) Events per 100 PY (95% CI) Adverse events URTI UTI Headache 95 (91.3) 20 (19.2) 18 (17.3) 20 (19.2) 478.5 (448.2, 510.3) 23.7 (17.4, 31.7) 22.7 (16.5, 30.5) 18.1 (12.6, 25.1) 64 (86.5) 12 (16.2) 15 (20.3) 8 (10.8) 506.5 (463.4, 552.6) 26.0 (17.0, 38.1) 32.0 (21.9, 45.1) 11.0 (5.5, 19.7) Serious AEs 19 (18.3) 15.0 (10.0, 21.5) 14 (18.9) 18.0 (10.7, 28.4) Severe AEs* 22 (21.2) 21.7 (15.6, 29.3) 7 (9.5) 11.0 (5.5, 19.7) Withdrawals due to AEs2,3 4 (3.8)

• 6 (8.1)
• Infections†

62 (59.6) 113.0 (98.6, 129.0) 40 (54.1) 154.9 (131.4, 181.2) Serious infections† 8 (7.7) 4.1 (1.8, 8.1) 6 (8.1) 7.0 (2.8, 14.4) Injection-related reactions 13 (12.5) 17.0 (11.7, 23.9) 7 (9.5) 9.0 (4.1, 17.1)

▪ There were no deaths or anaphylactic reactions1 ▪ The most commonly reported AEs were upper respiratory tract infection and urinary tract infection and were mild or moderate in severity, with similar frequencies in both treatment groups1 ▪ The number of withdrawals due to AEs was low in both studies2,3

*The overall satralizumab treatment period includes cumulative data from the DB and the OLE. †Severe AEs were defined as incapacitating AEs affecting the patient’s ability to work or to perform normal daily activities. ‡MedDRA SOC: infections and infestations. AE, adverse event; CCOD, clinical cut-off date; CI, confidence interval; MedDRA, Medical Dictionary for Regulatory Activities; PY, patient-years; SOC, system organ class; URTI, upper respiratory tract infection; UTI, urinary tract infection. Data on file.

▪ Rates of AEs and serious AEs did not increase with longer exposure to satralizumab ▪ Consistent with the double-blind period, the most frequently reported AEs in the overall satralizumab treatment period were those belonging to the SOC Infections and Infestations – The rates of the most frequently reported AEs were comparable with the double-blind period

The safety profile of satralizumab in the overall satralizumab treatment period was consistent with the double-blind period

Satralizumab, double-blind period N = 104; PY = 193.74 Overall satralizumab treatment period* (up to a CCOD of 7 Jun 19) N = 166; PY = 437.69 Patients n (%) Events per 100 PY (95% CI) Patients n (%) Events per 100 PY (95% CI) Adverse events URTI Nasopharyngitis UTI 95 (91.3) 20 (19.2) 19 (18.3) 18 (17.3) 478.49 (448.18, 510.31) 23.74 (17.38, 31.67) 17.03 (7.65, 23.47) 22.71 (16.50, 30.49) 153 (92.2) 38 (22.9) 37 (22.3) 29 (17.5) 418.79 (399.83, 438.41) 25.13 (20.66, 30.29) 20.11 (16.13, 24.77) 18.51 (14.70, 23.00) Serious AEs 19 (18.3) 14.97 (10.02, 21.50) 35 (21.1) 12.57 (9.47, 16.36) Severe AEs† 22 (21.2) 21.68 (15.62, 29.30) 34 (20.5) 15.08 (11.66, 19.18) Withdrawals due to AEs 4 (3.8)

• 7 (4.2)
• Infections‡

62 (59.6) 113.04 (98.56, 129.04) 109 (65.7) 112.41 (102.69, 122.79) Serious infections‡ 8 (7.7) 4.13 (1.78, 8.14) 16 (9.6) 3.88 (2.26, 6.22) Injection-related reactions 13 (12.5) 17.03 (11.73, 23.92) 21 (12.7) 12.11 (9.07, 15.84)

AE, adverse events; IST, immunosuppressants; OLE, open-label extension; PY, patient-years.

• 1. Yamamura T, et al. N Engl J Med 2019;381(22):2114–2124. 2. Traboulsee A, et al. Lancet Neurol 2020;19:402–412. 3. de Seze J, et al. Poster presented at ECTRIMS 2019, Stockholm,

Sweden, 11–13 September 2019. Poster no. P1614. 4. Data on File.

▪ Satralizumab significantly reduced the risk of relapse in patients with NMOSD, both as monotherapy and in combination with baseline IST in two phase 3 trials1,2 ▪ The overall rate of AEs and serious AEs was comparable between the placebo and satralizumab groups in the double-blind period3 ▪ Rates of AEs and serious AEs in the overall satralizumab treatment period were consistent with the double-blind period and did not increase with longer exposure to satralizumab4 ▪ The incidence, rate, and type of infections observed in either study did not change, and no unexpected emerging infections or serious infections were reported4 – The incidence and rate of serious infections (9.6%; 3.88 events/100PY) in the overall satralizumab treatment period was low and consistent with that reported in the double- blind period (7.7%; 4.13 events/100PY) – Almost all (97%) infections resolved, with the majority (73.3%) resolving within 14 days ▪ No deaths or anaphylactic reactions to satralizumab were reported in either study or in the OLE to date4

Satralizumab demonstrated a favourable safety and tolerability profile, which was maintained over a longer treatment period

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