CLINICAL TRIALS PROFILE FOR OCREVUS

All Clinical Trials for OCREVUS

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT03853746 ↗	Short-term B-cell Depletion in Relapsing Multiple Sclerosis	Active, not recruiting	National Multiple Sclerosis Society	Phase 4	2019-04-01	Several disease-modifying therapies (DMTs) have been shown to be effective in reducing the disease activity in patients with relapsing forms of multiple sclerosis (MS) but these treatments, often need to be used continuously for an unknown duration, rendering the long-term use extremely expensive. In addition, chronic administration of DMTs is often associated with undesirable side effects. Among these medications, B-cell depleting monoclonal antibodies might have the properties of an ideal group of medications: i) B-cell depleting antibodies have proven to be extremely potent in reducing or stopping the disease activity in relapsing MS, ii) B-cell depleting antibodies are very safe if used for a short period and use for a short duration may stop the inflammatory disease activity over long term, although current clinical practice and protocols are based on continuing B-cell depletion for an unknown period of time. Indeed, early phase clinical trials of rituximab and ocrelizumab suggested that a short course treatment with B-cell depleting antibodies can have long term effects and disease activity will not return even long after B-cell repopulation in the blood. This long-term effect might be related to the specific pattern of B-cell tolerance defect in patients with MS and the potential of its normalization with B-cell depleting antibodies. By analyzing the reactivity of recombinant antibodies expressed from single B-cells, the investigators' collaborators have demonstrated that the pattern of B-cell tolerance defect is different in people with MS who only display an impaired removal of developing autoreactive B-cells in the periphery while central B-cell tolerance in the bone marrow is functional in most patients. In contrast, patients with rheumatoid arthritis (RA), type-1 diabetes (T1D) or Sjögren's syndrome (SS) show defective central and peripheral B-cell tolerance checkpoints. As a consequence, while anti-B-cell therapy does not correct defective early B-cell tolerance checkpoints in T1D and only temporarily slows down autoimmune processes before newly generated autoreactive B-cells likely induce patient relapse, the investigators postulate that the efficacy of B-cell depleting antibodies in MS may be linked to the B-cell depleting antibodies' normal central B-cell tolerance and the production of a normal B-cell and T-cell compartment after anti-B-cell therapy. The investigators' goal is to provide proof-of-concept that a short duration of treatment with B-cell depleting antibodies can correct B-cell tolerance defects in MS and allow for medication-free prolonged freedom from disease activity, at least in a proportion of subjects with relapsing MS. In an open label study, 10 patients with active relapsing MS will be treated with two courses of ocrelizumab and will be followed clinically and radiologically for at least two and a half years. Time to the return of disease activity (defined as clinical relapses or new or enhancing lesions on the MRI) will be the primary outcome of the study. The investigators will harvest B-cells before starting the treatment and after B-cell repopulation and assess the central and peripheral tolerance defects. The investigators hypothesize that in most participants, the disease activity will not come back, and this prolonged response to anti cluster of differentiation 20 (CD-20) therapy is associated with normalization of B-cell tolerance defect in these patients. Considering the safety of this approach, it can be adopted widely among people with MS. Hence, the proposed B-cell analyses before and after B-cell depletion in people with MS will provide novel insights regarding the mechanisms underlying the beneficial effect of B-cell depleting antibodies and the potential long-term suppression of disease activity. This strategy can therefore improve the approach to treatment of many people with relapsing MS.
NCT02980042 ↗	Safety of Switching From Rituximab to Ocrelizumab in MS Patients	Completed	University of Colorado, Denver	Phase 3	2017-01-01	This is a prospective between and within group observational study to determine differences in tolerability, immunogenicity and safety related outcomes for 100 multiple sclerosis (MS) patients who have been administered at least two infusions of rituximab, six months apart and are willing to be switched to ocrelizumab compared to a 100 patients who are continuing on rituximab as a comparison cohort from the clinic population treated as part of clinical care.
NCT01466114 ↗	Estriol Treatment in Multiple Sclerosis (MS): Effect on Cognition	Recruiting	Synthetic Biologics (formerly Adeona Pharmaceuticals)	Phase 2	2011-10-01	Approximately 50% of people diagnosed with Multiple Sclerosis (MS) will develop problems with cognition. Currently, there are no FDA-approved treatments targeting cognitive function in Multiple Sclerosis. This trial will ascertain whether treatment with an estrogen pill, used in combination with standard MS anti-inflammatory drugs, can improve cognitive testing as compared to treatment with a placebo pill in combination with standard anti-inflammatory drugs in women with MS.
NCT01466114 ↗	Estriol Treatment in Multiple Sclerosis (MS): Effect on Cognition	Recruiting	University of California, Los Angeles	Phase 2	2011-10-01	Approximately 50% of people diagnosed with Multiple Sclerosis (MS) will develop problems with cognition. Currently, there are no FDA-approved treatments targeting cognitive function in Multiple Sclerosis. This trial will ascertain whether treatment with an estrogen pill, used in combination with standard MS anti-inflammatory drugs, can improve cognitive testing as compared to treatment with a placebo pill in combination with standard anti-inflammatory drugs in women with MS.

Clinical Trial Conditions for OCREVUS

Condition Name

Condition Name for OCREVUS
Intervention	Trials
Multiple Sclerosis	5
Secondary-progressive Multiple Sclerosis	2
Multiple Sclerosis, Relapsing-Remitting	2
Relapsing Multiple Sclerosis	2

Condition MeSH

Condition MeSH for OCREVUS
Intervention	Trials
Multiple Sclerosis	14
Sclerosis	13
Multiple Sclerosis, Relapsing-Remitting	5
Multiple Sclerosis, Chronic Progressive	5

Clinical Trial Locations for OCREVUS

Trials by Country

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Trials by Country for OCREVUS
Location	Trials
United States	75
Ukraine	23
Russian Federation	22
Italy	20
Brazil	17

Trials by US State

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−

Trials by US State for OCREVUS
Location	Trials
California	6
Colorado	4
Texas	4
New York	4
Michigan	3

Clinical Trial Progress for OCREVUS

Clinical Trial Phase

Clinical Trial Phase for OCREVUS
Clinical Trial Phase	Trials
Phase 4	7
Phase 3	6
Phase 2	2

Clinical Trial Status

Clinical Trial Status for OCREVUS
Clinical Trial Phase	Trials
Recruiting	9
Active, not recruiting	2
Completed	2

Clinical Trial Sponsors for OCREVUS

Sponsor Name

Sponsor Name for OCREVUS
Sponsor	Trials
Hoffmann-La Roche	3
Johns Hopkins University	2
Genentech, Inc.	2

Sponsor Type

Sponsor Type for OCREVUS
Sponsor	Trials
Other	37
Industry	7
NIH	1

OCREVUS: A Game-Changer in Multiple Sclerosis Treatment

Introduction to OCREVUS

OCREVUS (ocrelizumab) is a humanized monoclonal antibody developed by Roche, specifically designed to target CD20-positive B cells, which are implicated in the pathogenesis of multiple sclerosis (MS). Since its approval in 2017, OCREVUS has become a leading treatment option for both relapsing and primary progressive forms of MS.

Clinical Trials Update

OCARINA II Trial

The latest significant development in the clinical trials of OCREVUS comes from the Phase III OCARINA II study. This multicenter, global, randomized trial compared the pharmacokinetics, safety, radiological, and clinical effects of subcutaneous (SC) injections of OCREVUS with the traditional intravenous (IV) infusion.

• Efficacy: The trial demonstrated near-complete suppression of clinical relapses and brain lesions in MS patients, with a 97% reduction in relapse activity and a 97.2% reduction in MRI lesions over 48 weeks[1][4].
• Administration: The SC injection, administered twice yearly over a period of just 10 minutes, showed results consistent with the IV infusion, making it a more convenient option for patients[1][4].
• Safety: The most common adverse events were mild to moderate injection reactions such as erythema, pain, swelling, and pruritus[1].

Regulatory Approvals

The data from the OCARINA II trial have been submitted to health authorities globally, with both the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) accepting the submissions. Decisions on approval are expected in mid-2024 for the EMA and September 2024 for the FDA[1][4].

Market Analysis

Current Market Position

OCREVUS has established itself as a market leader in the MS treatment landscape. Approved for both relapsing multiple sclerosis (RMS) and primary progressive multiple sclerosis (PPMS), it is the only drug FDA-approved for the latter, a more rare and severe form of MS[3].

Sales Projections

• Short-Term Projections: By 2025, OCREVUS is predicted to reach annual sales of $6.8 billion, according to GlobalData[5].
• Long-Term Projections: By 2028, OCREVUS is forecasted to generate $7.6 billion in sales, driven by its high efficacy, good tolerability, and the newly approved shorter infusion time[3].
• Future Outlook: Even after its patent expiry in 2028-2029, OCREVUS is expected to continue generating significant sales due to its established efficacy and reliable treatment profile[2].

Competitive Landscape

The MS market is highly competitive, with several other treatments vying for market share.

• Kesimpta (ofatumumab): Developed by Novartis, Kesimpta is a monthly subcutaneous treatment that competes directly with OCREVUS. While Kesimpta has the advantage of self-administration at home, OCREVUS retains its leadership due to its first-to-market advantage and approval for PPMS[3].
• BTK Inhibitors: New entrants like tolebrutinib are expected to challenge the market dominance of OCREVUS and Kesimpta. However, their commercial reach will be limited by the anticipated approval of other BTK inhibitors within the forecast period[2].

Patient and Treatment Center Impact

Convenience and Accessibility

The introduction of the subcutaneous injection format of OCREVUS is set to expand its usage to treatment centers without IV infrastructure or with IV capacity limitations. This 10-minute injection can be administered twice yearly, significantly reducing the time and resources required for treatment compared to the traditional IV infusion[1][4].

Patient Satisfaction

The shorter infusion time approved by the FDA, reducing the treatment duration from 3.5 hours to just two hours, is expected to enhance patient satisfaction. This change, based on the ENSEMBLE PLUS study, has shown comparable safety and infusion reaction rates between the two infusion times[3].

Future Research and Development

There are over 30 ongoing clinical trials for OCREVUS, aimed at better understanding MS and its progression. These trials are crucial for expanding the therapeutic applications of OCREVUS and further solidifying its position in the MS treatment market[4].

Key Takeaways

• Clinical Efficacy: OCREVUS has demonstrated near-complete suppression of clinical relapses and brain lesions in MS patients through both IV and SC administration.
• Market Leadership: OCREVUS is projected to maintain its market leadership despite increasing competition, driven by its high efficacy and convenient dosing regimen.
• Regulatory Approvals: The SC injection format is pending approval by the EMA and FDA, expected in mid-2024 and September 2024, respectively.
• Patient Impact: The new SC injection and shorter infusion times are expected to enhance patient satisfaction and accessibility of the treatment.

FAQs

Q: What is OCREVUS and how does it work?

A: OCREVUS is a humanized monoclonal antibody that targets CD20-positive B cells, which are involved in the pathogenesis of multiple sclerosis. It is administered via intravenous infusion or subcutaneous injection.

Q: What are the key findings from the OCARINA II trial?

A: The OCARINA II trial showed near-complete suppression of clinical relapses and brain lesions in MS patients, with a 97% reduction in relapse activity and a 97.2% reduction in MRI lesions over 48 weeks.

Q: How does the subcutaneous injection of OCREVUS compare to the intravenous infusion?

A: The subcutaneous injection, administered twice yearly over 10 minutes, has shown results consistent with the intravenous infusion, making it a more convenient option for patients.

Q: What is the current market position of OCREVUS?

A: OCREVUS is the market leader in the MS treatment landscape, approved for both relapsing and primary progressive multiple sclerosis.

Q: What are the projected sales of OCREVUS by 2025 and 2028?

A: By 2025, OCREVUS is projected to reach $6.8 billion in sales, and by 2028, it is forecasted to generate $7.6 billion in sales.

Sources

1. Clinical Trials Arena: "Roche's OCREVUS SC shows promise in multiple sclerosis trial"
2. Drug Development: "Multiple Sclerosis Market to Generate Sales of $29.8 Billion by 2030"
3. Clinical Trials Arena: "Roche's Ocrevus set to top $7.6bn in sales by 2028"
4. Genentech Press Releases: "Genentech’s Subcutaneous OCREVUS: One Year Data"
5. The Pharma Letter: "Dominant Ocrevus predicted to hit $6.8 billion in sales by 2025"