Ocrevus™ (Ocrelizumab) is a prescription medication that was approved for usage by the US Food and Drug Administration (FDA) on March 28, 2017 and is now available in Canada as well for both relapsing-remitting MS (RRMS) and primary-progressive MS (PPMS). This is the disease-modifying therapy ever approved for primary progressive multiple sclerosis.
Ocrevus has received market approval in North America, South America, the Middle East, Ukraine and Australia, Switzerland.
Marketed by Genentech a member of the Roche Group Ocrevus is delivered as an intravenous (IV) infusion at your healthcare providers facilities or other qualified facilities.
Ocrelizumab is an anti-CD20 monoclonal antibody. It works by targeting CD20-positive B cells — the type of cells that are thought to play a role in the body’s abnormal immune response leading to damaged myelin in people with MS.
Ocrevus™ is delivered to the patient by intravenous infusion (IV) with the first dosage given as two separate infusions, two weeks apart. Each infusion will last about 2 hours and 30 minutes. These infusions will last about 3 hours and 30 minutes.
The medication is thus given to multiple sclerosis patients twice per year annually.
Pre-medication such as a corticosteroid or antihistamine may be called for by your healthcare provider to reduce infusion-related reactions. Infusion reactions can occur up to 24 hours after the infusion.
Results from three Phase III studies of the experimental medication Ocrevus™ (ocrelizumab) were published in the December 21, 2016 online issue of the New England Journal of Medicine (NEJM). Published information includes the full data from the OPERA I and OPERA II studies, for relapsing multiple sclerosis (RMS), and the ORATORIO study, for primary-progressive multiple sclerosis (PPMS).
All studies displayed positive results in treating both relapsing multiple sclerosis and progressive multiple sclerosis.
Relapsing MS Clinical Trial Results:
Two identical Phase III clinical trials were performed in relapsing multiple sclerosis known as the OPERA I and OPERA II studies. The medication was compared to high-dose Rebif® (interferon beta-1a) and displayed positive results.
Annualized relapse rates (ARR) were reduced by 46% (OPERA I) and 47% (OPERA II) in comparison to Rebif. Confirmed disability progression or CDP was also reduced both in 12 and 24-week examination by 43% (OPERA I) and 37% (OPERA II) respective.
Magnetic Resonance Imaging (MRI) findings displayer T1 gadolinium-enhancing lesions were reduced by 94% (OPERA I) and 95% (OPERA II). The total number of new and/or enlarging hyperintense T2 lesions was reduced by 77% (OPERA I) and 84% (OPERA II).
No evidence of disease activity or NEDA results increased. At 96 weeks the proportion of patients displaying NEDA activity was 64% (OPERA I) and 89% (OPERA II) respectively.
Progressive MS Clinical Trial Results:
The ORATORIO Phase III trial compared Ocrevus to placebo in individuals with primary-progressive MS (PPMS). In this study, the risk of confirmed disability progression (CDP) was reduced by 24 percent for at least 12 weeks and 25 percent for at least 24 weeks. The time required to walk 25 feet (Timed 25-Foot Walk) was reduced by 29 percent at 120 weeks.
In terms of MRI findings, the total volume of brain hyperintense T2 lesions was reduced by 3.4 percent over the 120-week time period. This was in contrast to a 7.4-percent increase experienced by individuals with PPMS in the placebo group. From week 24 to week 120, the rate of whole brain volume loss was reduced by 17.5 percent compared with placebo.
OCREVUS can cause infusion reactions, which can include pruritus, rash, urticaria, erythema, bronchospasm, throat irritation, oropharyngeal pain, dyspnea, pharyngeal or laryngeal edema, flushing, hypotension, pyrexia, fatigue, headache, dizziness, nausea, and tachycardia. In multiple sclerosis (MS) clinical trials, the incidence of infusion reactions in OCREVUS-treated patients [who received methylprednisolone (or an equivalent steroid) and possibly other pre-medication to reduce the risk of infusion reactions prior to each infusion] was 34-40%, with the highest incidence with the first infusion. There were no fatal infusion reactions, but 0.3% of OCREVUS-treated MS patients experienced infusion reactions that were serious, some requiring hospitalization.
A higher proportion of OCREVUS-treated patients experienced infections compared to patients taking REBIF or placebo. In RMS trials, 58% of OCREVUS-treated patients experienced one or more infections compared to 52% of REBIF-treated patients. In the PPMS trial, 70% of OCREVUS-treated patients experienced one or more infections compared to 68% of patients on placebo. OCREVUS increased the risk for upper respiratory tract infections, lower respiratory tract infections, skin infections, and herpes-related infections. OCREVUS was not associated with an increased risk of serious infections in MS patients. Delay OCREVUS administration in patients with an active infection until the infection is resolved.
Respiratory Tract Infections
A higher proportion of OCREVUS-treated patients experienced respiratory tract infections compared to patients taking REBIF or placebo. In RMS trials, 40% of OCREVUS-treated patients experienced upper respiratory tract infections compared to 33% of REBIF-treated patients, and 8% of OCREVUS-treated patients experienced lower respiratory tract infections compared to 5% of REBIF-treated patients. In the PPMS trial, 49% of OCREVUS-treated patients experienced upper respiratory tract infections compared to 43% of patients on placebo and 10% of OCREVUS-treated patients experienced lower respiratory tract infections compared to 9% of patients on placebo. The infections were predominantly mild to moderate and consisted mostly of upper respiratory tract infections and bronchitis.
In active-controlled (RMS) clinical trials, herpes infections were reported more frequently in OCREVUS-treated patients than in REBIF-treated patients, including herpes zoster (2.1% vs. 1.0%), herpes simplex (0.7% vs. 0.1%), oral herpes (3.0% vs. 2.2%), genital herpes (0.1% vs. 0%), and herpes virus infection (0.1% vs. 0%). Infections were predominantly mild to moderate in severity. There were no reports of disseminated herpes.
In the placebo-controlled (PPMS) clinical trial, oral herpes was reported more frequently in the OCREVUS-treated patients than in the patients on placebo (2.7% vs 0.8%).
Progressive Multifocal Leukoencephalopathy (PML)
PML is an opportunistic viral infection of the brain caused by the John Cunningham (JC) virus that typically only occurs in patients who are immunocompromised, and that usually leads to death or severe disability. Although no cases of PML were identified in OCREVUS clinical trials, JC virus infection resulting in PML has been observed in patients treated with other anti-CD20 antibodies and other MS therapies and has been associated with some risk factors (e.g., immunocompromised patients, polytherapy with immunosuppressants). At the first sign or symptom suggestive of PML, withhold OCREVUS and perform an appropriate diagnostic evaluation. MRI findings may be apparent before clinical signs or symptoms. Typical symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes.
Hepatitis B Virus (HBV) Reactivation
There were no reports of hepatitis B reactivation in MS patients treated with OCREVUS. Fulminant hepatitis, hepatic failure, and death, caused by HBV reactivation have occurred in patients treated with other anti-CD20 antibodies. Perform HBV screening in all patients before initiation of treatment with OCREVUS. Do not administer OCREVUS to patients with active HBV confirmed by positive results for HBsAg and anti-HB tests.
For patients who are negative for surface antigen [HBsAg] and positive for HB core antibody [HBcAb+] or are carriers of HBV [HBsAg+], consult liver disease experts before starting and during treatment.
Possible Increased Risk of Immunosuppressant Effects with Other Immunosuppressants
When initiating OCREVUS after an immunosuppressive therapy or initiating an immunosuppressive therapy after OCREVUS, consider the potential for increased immunosuppressive effect. OCREVUS has not been studied in combination with other MS therapies.
An increased risk of malignancy with OCREVUS may exist. In controlled trials, malignancies, including breast cancer, occurred more frequently in OCREVUS-treated patients. Breast cancer occurred in 6 of 781 females treated with OCREVUS and none of 668 females treated with REBIF or placebo. Patients should follow standard breast cancer screening guidelines.
USE IN SPECIFIC POPULATIONS
There are no adequate data on the developmental risk associated with use of OCREVUS in pregnant women. There are no data on B-cell levels in human neonates following maternal exposure to OCREVUS. However, transient peripheral B-cell depletion and lymphocytopenia have been reported in infants born to mothers exposed to other anti-CD20 antibodies during pregnancy. OCREVUS is a humanized monoclonal antibody of an immunoglobulin G1 subtype and immunoglobulins are known to cross the placental barrier.
There are no data on the presence of ocrelizumab in human milk, the effects on the breastfed infant, or the effects of the drug on milk production. Ocrelizumab was excreted in the milk of ocrelizumab-treated monkeys. Human IgG is excreted in human milk, and the potential for absorption of ocrelizumab to lead to B-cell depletion in the infant is unknown. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for OCREVUS and any potential adverse effects on the breastfed infant from OCREVUS or from the underlying maternal condition.
Females and Males of Reproductive Potential
Women of childbearing potential should use contraception while receiving OCREVUS and for 6 months after the last infusion of OCREVUS.
Most Common Adverse Reactions
RMS: The most common adverse reactions in RMS trials (incidence ≥ 10% and > REBIF) were upper respiratory tract infections (40%) and infusion reactions (34%)
PPMS: The most common adverse reactions in PPMS trials (incidence ≥ 10% and > placebo) were upper respiratory tract infections (49%), infusion reactions (40%), skin infections (14%), and lower respiratory tract infections (10%)
Considered the founder of the industry, Genentech, now a member of the Roche Group, has been delivering on the promise of biotechnology for over 40 years.
Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious or life-threatening medical conditions. We are among the world’s leading biotech companies, with multiple products on the market and a promising development pipeline.
Genetech Wesbite: https://www.gene.com
Ocrevus Website: https://www.ocrevus.com/
|Ocrevus RMS Patient Guide||Ocrevus PMS Patient Guide|