Longer-term data from the phase III open-label extension studies of OPERA I, OPERA II and ORATORIO have shown that patients who were treated with Ocrelizumab ( Ocrevus) continuously for six years or more had reduced risk of disability progression in relapsing multiple sclerosis ( RMS ) and primary progressive multiple sclerosis ( PPMS ).
These results suggest earlier treatment with Ocrelizumab reduces the risk of disability progression and this effect is sustained over time.
Additionally, new safety data as of January 2019 were announced, representing 4,611 patients with RMS and PPMS and 14,329 patient years of exposure to Ocrelizumab, across all clinical trials, and remain consistent with the medicine’s favourable benefit-risk profile.
Findings were presented at the 35th Congress of the European Committee for Treatment and Research in Multiple Sclerosis ( ECTRIMS ) in Stockholm, Sweden.
In the OPERA OLE, the proportion of RMS patients with 24-week confirmed disability progression ( CDP ) was lower for those treated with continuous Ocrelizumab ( total of six years on Ocrelizumab ) compared with patients who switched to Ocrelizumab after two years of Interferon beta-1a treatment in the double-blind period ( total of four years on Ocrelizumab ) ( 19% vs. 24%; p less than 0.05 ).
In the ORATORIO OLE, the proportion of PPMS patients with 24-week CDP was lower for those treated with continuous Ocrelizumab over six and a half years compared with patients who switched to Ocrelizumab from placebo after the double-blind period ( 52% vs. 65%; p=0.002 ).
Upper limb disability progression, measured by the nine-hole peg test ( 9-HPT ), was significantly reduced in patients who were continuously treated with Ocrelizumab compared with those who switched from placebo ( 31% vs. 43%; p=0.004 ).
Data have also shown earlier intervention with Ocrelizumab resulted in a 42% reduction in the risk of PPMS patients needing a wheelchair ( EDSS greater than or equal to 7 ) over 6.5 years compared with patients who started Ocrelizumab treatment after the double-blind period ( p=0.0112 ).
Additionally, data from the open-label phase IIIb CASTING study evaluating Ocrelizumab in patients with RRMS who had a suboptimal response to at least six months of treatment with one or two other disease modifying treatments ( DMTs ) were presented.
An interim analysis showed 87% of patients who switched to Ocrelizumab had no evidence of disease activity ( NEDA ) after 48 weeks of treatment.
A new, separate analysis from the same study showed that patients who switched from another DMT to Ocrelizumab reported greater satisfaction with Ocrelizumab after one year of treatment.
Patients reported satisfaction with its effectiveness, side effects, convenience and overall satisfaction, as measured by the self-reported Treatment Satisfaction Questionnaire for Medication vII ( TSQM vII ).
Furthermore, results from two phase IIIb studies, the CHORDS substudy in RRMS and the SaROD study in PPMS and RMS, have demonstrated patients treated with Ocrelizumab at a reduced infusion time showed no increased risk of serious, severe or life-threatening infusion-related reactions.
The current infusion time is approximately 3.5 hours and a majority of the patients in these studies completed infusions within 2.5 hours. Frequency of administration is highly important to patients and their healthcare providers and potentially shorter Ocrelizumab infusion times once every six months may improve the overall treatment experience.
In addition to consistent overall safety outcomes, new data on 267 pregnancies in MS patients from Ocrelizumab clinical trials and real-world use were also in line with previous reports, and the reviewed cases to date do not suggest an increased risk of adverse pregnancy outcomes in case of accidental exposure within a year of conception or during pregnancy.
Ocrelizumab is the first therapy approved for both RMS ( including clinically isolated syndrome, RRMS and active, or relapsing, SPMS ) and PPMS, with six-monthly dosing.
Ocrelizumab is a humanised monoclonal antibody designed to target CD20-positive B cells, a specific type of immune cell thought to be a key contributor to myelin and axonal damage. This nerve cell damage can lead to disability in people with multiple sclerosis.
Based on preclinical studies, Ocrelizumab binds to CD20 cell surface proteins expressed on certain B cells, but not on stem cells or plasma cells, suggesting that important functions of the immune system may be preserved.
Ocrelizumab is administered by intravenous infusion every six months. The initial dose is given as two 300 mg infusions given two weeks apart. Subsequent doses are given as single 600 mg infusions. ( Xagena )
Source: Roche, 2019