Roche Holding Ltd · SIX:RO
Roche — Technical Presentation (May 2020)
24 slides from Roche's technical presentation, May 26, 2020
Slide 1: Safety of Ocrelizumab in Multiple Sclerosis: Updated Analysis in Relapsing and Primary Progressive MS
Safety of Ocrelizumab in Multiple Sclerosis: Updated Analysis in Patients With Relapsing and Primary Progressive Multiple Sclerosis SL Hauser, L Kappos, X Montalban, L Craveiro, R Hughes, K Prajapati, H Koendgen, A Pradhan, JS Wolinsky Phase II (NCT00676715); OPERA I (NCT01247324); OPERA II (NCT0141
Slide 2: Disclosures
Disclosures Stephen L Hauser serves on the board of trustees for Neurona and on Richard Hughes is an employee and shareholder of F. Hoffmann-La scientific advisory boards for Alector, Annexon, Bionure and Molecular Roche Ltd. Stethoscope, and has received travel reimbursement and writing assistance
Slide 3: Background and objectives
Background and objectives • The safety and efficacy of OCR in patients with MS have been characterised in Phase II and Phase III clinical trials1–3 • OCR reduced disease activity and disability progression in patients with RMS vs IFN β-1a2 and PPMS vs placebo3 • In the Phase III trials, the most com
Slide 4: Methods
Methods • Safety analyses are based on integrated data for all patients who received OCR in the following MS clinical trials: – OPERA OLE: The Phase III OPERA I (NCT01247324) and OPERA II (NCT01412333) clinical trials, and OLE periodsa – ORATORIO OLE: The Phase III ORATORIO (NCT01194570) clinical tr
Slide 5: Overview of Phase II/III/IIIb studies and patient exposure
Overview of Phase II/III/IIIb studies and patient exposure • As of August 2019, 5,051 patients with MS had received OCR across multiple clinical trials Phase III N=1,311 Phase II in RRMSa Open-label extension PY=3,054 Phase III OPERA I/II in RMSb Open-label extension CTP + OLE N=2,092 ORATORIO in PP
Slide 6: Over 6.5 years, the safety profile of ocrelizumab remained consistent
Over 6.5 years, the safety profile of ocrelizumab remained consistent Controlled treatment perioda Controlled treatment period/OLEb OPERA ORATORIO OPERA ORATORIO Ocrelizumab Adverse event all-exposure Rate per 100 PY (95% CI) IFN β-1a Ocrelizumab Placebo Ocrelizumab Ocrelizumab Ocrelizumab populatio
Slide 7: Rate of serious infections remained generally stable over 6.5 years
Over 6.5 years, the rate of serious infections in the OCR all-exposure population remained generally stable with no significant year-on-year variation Yearly rate of serious infections: Yearly rate of serious infections: RMS and PPMS populations OCR all-exposure 10 10 9 9 Event rate per 100 PY Event
Slide 8: Cumulative standardised incidence rates of malignancies and female breast cancer remained stable
Cumulative standardised incidence rates of all malignancies and female breast cancer remained stable over time and within the range reported in registries All malignancies: Age- and sex-standardised “Age at enrollment” methodology “Age at event onset” methodology No increased risk Increased risk 0.8
Slide 9: Overview of COVID-19 reporting in OCR-treated patients with MS
Overview of COVID-19 reporting in OCR-treated patients with MS • As of 30 April 2020, there have been 100 validated reports relating to the ongoing COVID-19 pandemic in OCR-treated patients with MS 100 valid COVID-19 cases 74 confirmeda 26 suspectedb 26 hospitalised 74 not hospitalised 19 recovered
Slide 10: Conclusions
Conclusions • The reported rates of AEs in OPERA OLE, ORATORIO OLE and the OCR all-exposure population continue to be generally consistent with those seen during the CTP of the Phase III trials • In the OCR all-exposure population, the rate of serious infections remained low and generally consistent
Slide 11: Acknowledgements
Acknowledgements We would like to thank all patients, their families, the investigators, the independent data monitoring committees, and the Study Steering Committees who participated in these trials and the associated open-label extensions: • Phase II, OPERA I, OPERA II, ORATORIO, VELOCE, CHORDS, C
Slide 12: Supplemental materials
Supplemental materials • Additional methods • Overview of study designs • Treatment exposure • AEs leading to treatment discontinuation • Potential serious opportunistic infections, including PML • Standardised incidence rates of all malignancies and female breast cancer • Yearly crude incidence rat
Slide 13: Methods: Malignancies
Methods: Malignancies • Age- and sex-standardised incidence rates of all malignancies (excluding NMSC), and age-standardised incidence rates of female breast cancer were compared to rates from real-world epidemiological sources, both MS-specific (Danish MS Registry)1 and for the general population (
Slide 14: Overview of study designs
Overview of study designs Population Naïve/pre- Number of Overall PY Duration of Entering Objective Current Study name (start date) treated (%)a Design Treatment patients (Aug 2019) main study OLE?b of study Primary endpoint status Phase II RRMS Naïve and Controlled OCR 2000 mg 55 1,193 96 weeks Yes
Slide 15: Overview of study designs (cont.)
Overview of study designs (cont.) Population Naïve/pre- Number of Overall PY Duration of Entering Objective Current Study name (start date) treated (%)a Design Treatment patients (Aug 2019) main study OLE?b of study Primary endpoint status VELOCE RMS Naïve and Controlled OCR 2000 mg 68 313 24 weeks
Slide 16: Overview of study designs (cont.)
Overview of study designs (cont.) Population Naïve/pre- Number of Overall PY Duration of Entering Objective Current Study name (start date) treated (%)a Design Treatment patients (Aug 2019) main study OLE?b of study Primary endpoint status OBOE RMS Naïve and Single arm OCR 600 mg 88 250 52 weeks Yes
Slide 17: Treatment exposure
Treatment exposure • In the OCR all-exposure population, over 50% of patients (2,855) received ≥5 doses Phase III CTP + OLE (N=2,092)a OPERA CTP/OLE ORATORIO CTP/OLE (N=1,448)a (N=644)a OCR all-exposure (N=5,051)b Median (range) age at start of 38.0 (18–58) 47.0 (30–59) 37.0 (18–59) treatment, years
Slide 18: IRRs, neoplasms and infections were the most common AEs leading to discontinuation
IRRs, neoplasms and infections were the most common AEs leading to discontinuation in the OCR all-exposure population MedDRA SOC Number of MedDRA SOC Number of MedDRA preferred term patients MedDRA preferred term patients Overall total number of patients 167 Injury, poisoning and procedural complica
Slide 19: AEs leading to discontinuation (cont.)
IRRs, neoplasms and infections were the most common AEs leading to discontinuation in the OCR all-exposure population (cont.) MedDRA SOC Number of MedDRA SOC Number of MedDRA preferred term patients MedDRA preferred term patients Psychiatric disorders 13 General disorders and administration site con
Slide 20: AEs leading to discontinuation (cont.)
IRRs, neoplasms and infections were the most common AEs leading to discontinuation in the OCR all-exposure population (cont.) MedDRA SOC Number of MedDRA SOC Number of MedDRA preferred term patients MedDRA preferred term patients Hepatobiliary disorders 3 Immune system disorders 2 Hepatitis 1 Haemop
Slide 21: Potential serious opportunistic infections
Potential serious opportunistic infections • As of August 2019, the incidence of potential SOIs in the OCR all-exposure population was low, at a rate of 0.08 per 100 PY (95% CI 0.04–0.13) – The rates remained stable year-on-year compared with the rates observed during the CTP (0.09 per 100 PY; 95% C
Slide 22: Standardised incidence rates of malignancies and female breast cancer within registry ranges
Over 6.5 years, the standardised incidence rates of all malignancies and female breast cancer remained within the range reported in registries Incidence of all malignancies Incidence of female breast cancer Age- and sex-standardised Age-standardised Incidence of all malignanciesa Standardised incide
Slide 23: No significant year-on-year variation in incidence of malignancies and breast cancer
Over 6.5 years, no significant year-on-year variation was observed in the incidence rates of all malignancies and female breast cancer All malignancies Female breast cancer 2.0 2.0 AEs per 100PY (95% CI) AEs per 100PY (95% CI) 1.6 0.26 0.52 0.69 0.66 0.46 0.63 1.6 0.03 0.33 0.42 0.27 0.11 0.00 (0.13
Slide 24: COVID-19 patient demographics, symptom severity and outcomes in OCR-treated patients with MS
COVID-19 patient demographics, symptom severity and outcomes in OCR-treated patients with MS All cases Confirmed cases Cases reported as hospitalised (n=100) (n=74) (n=26)a Patient demographics Mean age (range) 42.3 (23–59)b 42.9 (23–59)c 44.1 (30–59)d Gender, n (%) Male 28 (28) 21 (28) 11 (42) Fema