New Ocrevus Data, Post-FDA Approval, Supports Range of Benefits, Genentech’s Hideki Garren Says

New Ocrevus Data, Post-FDA Approval, Supports Range of Benefits, Genentech’s Hideki Garren Says
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Ocrevus (ocrelizumab), Genentech’s humanized anti-CD20 monoclonal antibody, continues to show clear evidence that it helps to slow disease progression and enable better function — including in the hands and limbs — of relapsing multiple sclerosis (MS) and primary progressive multiple sclerosis (PPMS), latest data reveals.

The first FDA-approved therapy — in March 2017 —  tackling both MS forms, Ocrevus was quickly considered a “game-changing MS treatment.”  Last week, Multiple Sclerosis News Today interviewed Dr. Hideki Garren, Genentech’s Group Medical Director of Product Development Neuroscience, about current views and the data collected to date on the therapy’s effectiveness.

“We have been very pleased by the overwhelmingly positive reception that Ocrevus has had from the MS community and regulatory bodies across the world. As of the end of 2017, over 30,000 people have been treated with Ocrevus, and it has been approved for use in 50 countries globally,” Garren said.

“Ongoing data for Ocrevus support the need for the medicine and reinforce why we have seen such positive uptake in the U.S. … and the recent approvals across the globe, such as the recent EU approval,” he added.

At the ACTRIMS 2018 Forum that took place Feb. 1–3, Genentech presented several posters with new data, results that “expand on prior presentations by showing the impact of Ocrevus on functions that are important for the day-to-day activities of people with MS, such as hand/arm function and visual acuity,” said Garren.

In one presentation, researchers assessed the proportion of relapsing MS patients who achieved NEPAD in the Phase 3 OPERA trials (NCT01247324 and NCT01412333), a new endpoint that stands for “no evidence of progression or active disease.” NEPAD includes hand/arm function and walking assessments, two new parameters that “are highly relevant for people with MS because it is these abilities that allow them to maintain their independence and quality of life,” Garren said.

NEPAD is also a more comprehensive measure of disability progression, and is considered a clinically meaningful measurement of overall disease activity and disability progression in people with both relapsing MS and PPMS, Garren emphasized.

The analysis showed that, compared to Rebif (interferon beta-1a), treatment with Ocrevus increased the proportion of patients reaching NEPAD at week 96 post-treatment by 82 percent. These results are in agreement with previous Ocrevus data that had NEDA (no evidence of disease activity) as its endpoint — treatment for the same period led to 75 percent of patients achieving NEDA compared with Rebif.

“The results here show that an even higher proportion of people with MS maintain no signs of disease progression on a more comprehensive measure, NEPAD,” Garren said.

“Maintaining NEPAD is important because it signifies that a patient has no relapses, no confirmed disability progression measured by the Expanded Disability Status Scale (EDSS), no progression equal to or above 20 percent on the timed 25-foot walk (T25-FW [assessing exercise capacity]) and the nine-hole peg test (9-HPT [assessing finger dexterity]), no gadolinium-enhancing T1 MRI lesions and no new or enlarging T2 MRI lesions,” Garren said.

Treatment also lowered the risk of severe progression of upper extremity impairments for both hands (dominant and non-dominant) in PPMS patients compared to placebo controls, a new analysis of the ORATORIO trial (NCT01194570) showed.

These findings represent a key step in treating PPMS patients, those at higher risk of losing hand and arm function compared to relapsing MS patients, Garren said.

“Ocrevus reduced the risk of more severe upper extremity disability progression in patients with PPMS compared with placebo in an exploratory analysis of the ORATORIO study,” he said. “Slowing disability progression in the hands or arms — also known as upper extremity function — is important to help maintain independence and quality of life.”

Visual impairment is also a common and often irreversible clinical manifestation of the disease. Patients can experience “reduced low-contrast vision, which can significantly impact the ability to perform key tasks of daily functioning (e.g., driving, reading),” Garren said. About half of MS patients progress to optic neuritis — inflammation of the optic nerve in the eye.

Compared to Rebif, treatment with Ocrevus led to significant visual improvements in a specific subgroup of relapsing MS patients with visual impairment — a 54 percent improvement in the seven-letter change between the two groups, a parameter considered clinically meaningful, said Garren.

Ocrevus-treated patients showed a better ability to read low-contrast letters over the course of the two OPERA trials, while Rebif-treated patients did not.

Another ACTRIMS presentation focused on Ocrevus’ safety and long-term benefit-risk profile. Clinical trial results showed infusion-related reactions (IRR) to be the most common overall adverse events in Ocrevus-treated patients compared to those given Rebif or placebo.

However, according to Garren, these reactions are manageable and can be minimized.

“IRRs are most often seen during the first infusion, generally mild-to-moderate in severity,” he said. “Pre-medication with methylprednisolone and an antihistamine must be administered to reduce IRRs. In addition, slowing or stopping infusions, where needed, can help manage IRRs.”

Real-world clinical data, also presented at the meeting, supported this tendency — 12.9 percent of patients receiving Ocrevus had an IRR during one of the first two infusions — in contrast to data from the clinical trials, where the percentage was higher (34.3 and 39.9 percent).

But this data, being collected by the Cleveland Clinic Mellen Center for Multiple Sclerosis, is still preliminary, and Garren noted that “initial findings from the three-month follow-up are too early to compare to clinical trial results.”

The goal is to assess Ocrevus’ efficacy, safety, and tolerability in clinical practice, and “real-world data in conjunction with clinical trial data may further help to inform treatment decisions and improve patient outcomes,” Garren added.

Overall, “data presented at ACTRIMS continue to reinforce a favourable benefit-risk profile and effect of Ocrevus in reducing disease activity and disability progression in patients with [relapsing] MS and PPMS, including MS-related symptoms like hand/arm function and vision acuity that can have a substantial impact on the day-to-day lives of people with MS,” he said.

“Given the large number of over 30,000 people with MS already taking Ocrevus, we are committed to continuing to provide data to help better understand how Ocrevus may benefit people with MS,” Garren concluded.

 

Patricia holds her Ph.D. in Cell Biology from University Nova de Lisboa, and has served as an author on several research projects and fellowships, as well as major grant applications for European Agencies. She also served as a PhD student research assistant in the Laboratory of Doctor David A. Fidock, Department of Microbiology & Immunology, Columbia University, New York.
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Patricia holds her Ph.D. in Cell Biology from University Nova de Lisboa, and has served as an author on several research projects and fellowships, as well as major grant applications for European Agencies. She also served as a PhD student research assistant in the Laboratory of Doctor David A. Fidock, Department of Microbiology & Immunology, Columbia University, New York.
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