Indications for: OCREVUS
Relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease. Primary progressive MS.
Relapsing Forms of Multiple Sclerosis (RMS)
The efficacy was evaluated in 2 identical randomized, double-blind, double-dummy, active comparator-controlled clinical trials in patients with RMS treated for 96 weeks (Study 1 and Study 2).
Patients received Ocrevus 600 mg every 24 weeks (given as an initial treatment of two 300 mg IV infusions administered 2 weeks apart, and subsequent doses as a single 600 mg IV infusion) and placebo SC injections 3 times per week. The active comparator, Rebif, was administered 44 mcg as SC injections 3 times per week and placebo IV infusions every 24 weeks.
The primary endpoint for both studies was the annualized relapse rate (ARR). Additional outcome measures included the proportion of patients with confirmed disability progression, the mean number of MRI T1 gadolinium (Gd)-enhancing lesions at Weeks 24, 48, and 96, and new or enlarging MRI T2 hyperintense lesions.
Study 1 included 821 patients who were randomly assigned 1:1 to receive Ocrevus or Rebif. Study 2 included 835 patients who were randomly assigned 1:1 to receive Ocrevus or Rebif.
Results from Study 1 showed the following key clinical and MRI endpoints for Ocrevus vs Rebif, respectively:
ARR: 0.156 vs 0.292 (relative reduction, 46%; P <.0001)
Proportion relapse-free: 83% vs 71%
Mean number of T1 Gd-enhancing lesions per MRI: 0.016 vs 0.286 (relative reduction, 94%; P <.0001)
Mean number of new and/or enlarging T2 hyperintense lesions per MRI: 0.323 vs 1.413 (relative reduction, 77%; P <.0001)
Results from Study 2 showed the following key clinical and MRI endpoints for Ocrevus vs Rebif, respectively:
ARR: 0.155 vs 0.290 (relative reduction, 47%; P <.0001)
Proportion relapse-free: 82% vs 72%
Mean number of T1 Gd-enhancing lesions per MRI: 0.021 vs 0.416 (relative reduction, 95%; P <.0001)
Mean number of new and/or enlarging T2 hyperintense lesions per MRI: 0.325 vs 1.904 (relative reduction, 83%; P <.0001)
In a pooled analysis of Study 1 and Study 2, the proportion of patients with 12-week confirmed disability progression was significantly lower for the Ocrevus arm compared with the Rebif arm, 9.8% vs 15.2%, respectively (risk reduction, 40%; P =.0006).
Primary Progressive Multiple Sclerosis (PPMS)
The efficacy of Ocrevus was evaluated in 488 patients with PPMS in a randomized, double-blind, placebo-controlled clinical trial (Study 3). Patients were randomly assigned 2:1 to receive either Ocrevus 600 mg or placebo as two 300 mg intravenous infusions 2 weeks apart every 24 weeks for at least 120 weeks.
Neurological assessments were conducted every 12 weeks. Patients were evaluated using an MRI scan at baseline and at weeks 24, 48, and 120. The primary endpoint was the time to onset of disability progression attributable to MS confirmed to be present at the next neurological assessment at least 12 weeks later.
Results showed following key clinical and MRI endpoints for Ocrevus vs placebo, respectively:
Proportion of patients with 12-week confirmed disability progression: 32.9% vs 39.3% (risk reduction, 24%; P =.0321)
Mean change in volume of T2 lesions from baseline to week 120: -0.39 vs 0.79 (P <.0001)
In the overall population, 49% of Ocrevus-treated patients had a 20% worsening of the timed 25-foot walk confirmed at 12 weeks compared with 59% of placebo-treated patients (risk reduction, 25%).
Screen for HBV infection and test for serum immunoglobulins prior to initiation. Premedicate with corticosteroid and antihistamine prior to each infusion; may consider antipyretic. Initially 300mg by IV infusion, followed by a second 300mg infusion 2 weeks later, then subsequently as one 600mg infusion every 6 months. For infusion rates, duration, and dose modifications: see full labeling.
Active HBV infection. History of life-threatening infusion reaction to ocrelizumab.
Monitor for infusion reactions during and at least 1hr after therapy completion; permanently discontinue if life-threatening infusion reactions occur; treat appropriately. Delay Ocrevus in those with active infection until resolved. Discontinue if serious herpes infection occur; withhold until resolved. Withhold at first sign/symptom of progressive multifocal leukoencephalopathy (PML) and evaluate; discontinue if PML is confirmed. HBV reactivation: screen all patients for HBV; if positive HBsAg/anti-HB results, do not administer Ocrevus. Monitor serum immunoglobulin levels during and after therapy, until B-cell repletion, and esp. during recurrent serious infections. Consider discontinuing therapy in those with opportunistic or recurrent serious infections, and if prolonged hypogammaglobulinemia requires IV immunoglobulins. Increased risk of malignancy (including breast cancer). Monitor for immune-mediated colitis during therapy; evaluate promptly if signs/symptoms occur. Complete all immunizations according to guidelines at least 4 weeks (for live or live-attenuated vaccines) or at least 2 weeks (for non-live vaccines) prior to initiation. Infants born to mothers treated during pregnancy: do not administer live or live-attenuated vaccines before confirming B-cell recovery; non-live vaccines may be given prior to recovery, but should consider assessment of vaccine immune response. Advise females of reproductive potential to use effective contraception during and for 6 months after the last dose. Pregnancy. Nursing mothers.
CD20-directed cytolytic monoclonal antibody.
Concomitant live or live-attenuated vaccines: not recommended during treatment and until B-cell repletion. May interfere with the effectiveness of non-live vaccines. Additive immunosuppressive effects with other immunosuppressants; consider the duration and effects when switching from immunomodulators (eg, corticosteroids, daclizumab, fingolimod, natalizumab, teriflunomide, mitoxantrone).
Upper/lower respiratory tract infections, infusion reactions (eg, pruritus, rash, urticaria, erythema, bronchospasm, throat irritation, others), skin infections; herpes virus-associated infections.
Constant clearance was estimated at 0.17 L/day, and initial time-dependent clearance at 0.05 L/day, which declined with a half-life of 33 weeks. The terminal elimination half-life was 26 days.
Generic Drug Availability:
Single-dose vial (10mL)—1