First-Line Ocrelizumab Use for Relapsing-Remitting Multiple Sclerosis in the United States: Trend and Comparison to Glatiramer Acetate and Dimethyl Fumarate

Virginia R. Schobel, MSc; Jennifer Robinson

Figure 1 Figure 2 Percent of Neurologists Who Agree with Figure 4 Table 1 Current Age Category Allocation: By DMT First-Line RRMS DMT Share: Trend Statement Agreement: Trend Gender and Current Age: By DMT Background 6% “I am comfortable using ocrelizumab as a first-line DMT 11% 10% 56+ Percent Age (mean In March 2017, ocrelizumab (OCR) was approved for the treatment of relapsing-remitting 2016 (n=777) 2017 (n=801) 2018 (n=758) 2019 (n=722) for patients with RMS” years Mean: 30% male years) and primary progressive multiple sclerosis (MS), irrespective of prior therapy exposure. The 31% 31% 2017 38% Glatiramer relapsing-remitting MS (RRMS) indication was updated in July 2019 to encompass all 38% 3.09 40 to 55 (n=274) years acetate 29% 39.6 relapsing forms of MS (RMS), including clinically isolated syndrome, RRMS, and active (n=225) secondary progressive MS. 17% 39% 2018 37% 30 to 39 Dimethyl 57% 2017 3.582017 36% 8% (n=213) years fumarate 34% 36.9

Objective (n=125) Percent of audit audit of patients Percent Percent of audit audit of patients Percent 22% 25% 18 to 29 Ocrelizumab 2019 16% 29% 41.3 To trend OCR uptake among previously treatment-naïve RRMS patients and compare 58%2017 3.652017 years (n=58) Glatiramer acetate Dimethyl fumarate Ocrelizumab (n=199) characteristics of RRMS patients initiated on first-line OCR to those initiated on one of the Glatiramer Dimethyl Ocrelizumab more established platform disease-modifying therapies (DMTs), glatiramer acetate (GA) or *Note: tested, but no significant differences *Superscripts represent statistically significant differences acetate (n=225) fumarate (n=125) (n=58) *Note: tested, but no significant differences dimethyl fumarate (DMF). Figure 3 Figure 5 Unfavorable Long-Term Prognostic Profile Figure 6 Impact of Statement Agreement on First-Line RRMS Share Disability Progression Status: By DMT Methods “I am comfortable using ocrelizumab as a first-line DMT for patients with RMS” Based Upon Concerning Risk Factors: By DMT Glatiramer Glatiramer acetate (n=225) 12% 70% 17% Disagree [A] Neutral [B] Agree [C] acetate A retrospective, cross-sectional chart audit of MS patients who initiated their first DMT no n=22 physicians; n=5 physicians; n=111 physicians; 15% more than three months prior (i.e., new start patients) has been conducted with U.S. n=75 patients n=220 patients n=247 patients (n=225) 37% [A] neurologists (2016 n=242; 2017 n=274; 2018 n=213; 2019 n=204) each December. Data Dimethyl fumarate 33% (n=125) 10% 66% 23% were based on contributed RRMS patient chart reviews (2016 n=777; 2017 n=801; 2018 29% Dimethyl fumarate n=758; 2019 n=722). GA includes patients treated with either a branded or generic agent. 20% 16% 18% A (n=125) Ocrelizumab Poster abstract was updated with 2019 data. 15% [B] 21% 59% 21% 10% (n=58) 7% Ocrelizumab AB Results audit of patients Percent 1% (n=58) 35% Quickly progressing Slowly progressing Stable Improving [C] Glatiramer acetate Dimethyl fumarate Ocrelizumab Percent of audit patients In 2019, OCR was prescribed to 8%, GA to 31%, and DMF to 17% of new start RRMS Percent of audit patients *Superscripts represent statistically significant differences *Superscripts represent statistically significant differences *Note: tested, but no significant differences patients — stable with prior years (Figure 1). Comfort using Ocrevus first line for RMS patients has increased over time (58% vs. 38% of neurologists in 2017; Figure 2). Figure 7 Figure 8 Level of Disability on Modified Rankin Scale: By DMT Reasons More Impactful in the Selection of Ocrelizumab as First-Line DMT Neurologists’ agreement with this statement correlated significantly with OCR share (Figure Glatiramer acetate (n=225) [A] Dimethyl fumarate (n=125) [B] Ocrelizumab (n=58) [C] Glatiramer acetate (n=211) [A] Dimethyl fumarate (n=124) [B] Ocrelizumab (n=58) [C] 3). Gender, mean age, and age category allocation did not differ between treatment AB AB 50% subgroups (Figure 4, Table 1). RRMS patients initiated on OCR were more likely to have a C 49% 55% AB 41% 53% perceived unfavorable long-term prognosis (OCR: 35%, GA: 15%, DMF: 16%; Figure 5) AB 27% 31% 38% 41% AB and to be experiencing disability progression (OCR: 21%, GA: 11%, DMF: 9%; NS; Figure 21% 21% 32% patients 19% 29% 6). In comparison, DMF patients were more likely to have no symptoms per the modified 14% 11% Percent of audit audit of Percent 6% 19% Rankin Scale (OCR: 14%, GA: 27%, DMF: 31%; Figure 7). OCR and DMF patients had a 4% 1% 1% 3% 14% 17% 14% 8% 12% greater mean T2 lesion burden at the most recent MRI scan (OCR: 5.8, GA: 3.8, DMF: 5.6) 0=No symptoms 1=No significant disability 2=Slight disability 3=Moderate disability 4=Moderately severe and, since first under the contributing neurologist’s care, OCR patients were more likely to disability My belief that this was Desire for a high Preference for the The specific MOA have had a relapse(s) (OCR: 48%, GA: 22%, DMF: 23%), decreased walking speed (OCR: Clinical Disease Activity Levels: By DMT Table 2 the best option efficacy agent dosing schedule 32%, GA: 10%, DMF: 9%), and/or confirmed disability progression over three months Glatiramer acetate [A] Dimethyl fumarate [B] Ocrelizumab [C] *Superscripts represent statistically significant differences (OCR: 26%, GA: 13%, DMF: 5%; Table 2). Best option belief, high efficacy desire, dosing Figure 9 Modified Rankin scales score (mean) AB schedule preference, and mechanism of action preference played significantly more of a 1.04 (n=225) 0.95 (n=125) 1.59 (n=58) Influence of Efficacy Need Versus Safety Risk Tolerance on Brand Selection: By DMT Kurtzke EDSS (mean) 1.80 (n=203) 1.79 (n=123) 2.50AB (n=54) role in the first-line selection of OCR compared to GA or DMF (Figures 8 and 9). Need for high efficacy Number of T2 lesions at most recent MRI 25% 3.76 (n=207) 5.64A (n=122) 5.76A (n=54) 42%A agent outweighs any (mean) 60%A safety risk (8-10) Conclusions Confirmed activity occurrences since Glatiramer acetate Dimethyl fumarate under contributing physician's care Ocrelizumab Regardless of neurologists’ perceived comfort with first-line OCR, use among new start (n=109) (n=65) (n=31) C Balance between efficacy (percent of audit patients; must have been 62% RRMS patients has remained flat during the first three years of availability. Compared to [A] [B] [C] need and safety risk under care for more than three months) 52% tolerance (4-7) platform DMTs, OCR is most likely to be selected when a high efficacy agent is required Relapse(s) 22% 23% 48%AB 36% due to risk factors suggesting a poor long-term prognosis at the time of DMT treatment Decreased walking speed 10% 9% 32%AB 13% Not at all comfortable initiation. 6% exposing patient to safety EDSS progression over three months 13% 5% 26%B risk (1-3) Disclosures: Glatiramer acetate Dimethyl fumarate Ocrelizumab A Virginia Schobel and Jennifer Robinson are employees of Spherix Global Insights, an independent market intelligence firm, and have received no industry EDSS progression over six months 6% 6% 19% (n=211) (n=124) (n=58) funding to conduct and report on this study. *Superscripts represent statistically significant differences [A] [B] [C]