Marco Meglio

Two-year findings from the phase 3b CHORDS study (NCT02637856) demonstrated that patients with relapsing-remitting multiple sclerosis (RRMS) receive the benefits of ocrelizumab (Ocrevus; Genentech) treatment over 2 years despite having a suboptimal response with previous disease-modifying therapy (DMT).

The modified intention-to-treat (mITT) population included 576 patients, 48.1% of which were free of all protocol-defined events following treatment with ocrelizumab 600 mg. More specifically, freedom of relapse, gadolinium-enhancing (GdE) lesions, and new/enlarging T2 lesions occurred in 89.6%, 95.5%, and 59.5% of patients, respectively.

, the 8th Joint ECTRIMS-ACTRIMS meeting, September 11–13, 2020, by Bianca Weinstock-Guttman, MD, neurologist, Buffalo General Medical Center, the data also showed a 24-week confirmed disability progression (CDP) in 89.6% of patients over 96 weeks for those treated with ocrelizumab.

Weinstock-Guttman and colleagues found similar results for the primary end point in those who received 1 versus >1 prior DMT (50.9% vs 44.5%) as well as for individual events (relapse: 90.% vs 89.2%; T1 GdE lesion: 95.8% vs 95.1%; new/enlarging T2 lesion: 61.4% vs 57.1%; 24-week CDP: 90.9% vs 87.9%). Notably, the adjusted annualized relapse rate (ARR) assessed in the intention-to-treat (ITT) population over 96 weeks was 0.046.

Stable changes in Expanded Disability Status Scale (EDSS), defined as a <1-point change, occurred in 61.5% of the population. Improvements in EDSS, defined as ≥1-point decrease, occurred in 22.7% of patients. There were no deaths or new safety signalsobserved.

Among the 608 patients in the ITT population, the mean time since diagnosis was 4.2 years (standard deviation [SD], 3.03). The most frequently used DMTs prior to enrollment included glatiramer acetate (49.3%), dimethyl fumarate (35.4%) and fingolimod (20.1%).

Ocrelizumab, approved in 2017 for the treatment of relapsing forms of MS, including clinically isolated syndrome, as well as secondary progressive and primary progressive disease, had 

additional data from the phase 3b CASTING study

 (NCT02861014) presented at ECTRIMS 2020.

A pair of datasets from that study suggested that patients treated with the agent experienced high rates of no evidence disease activity (NEDA) status regardless of prior DMT exposure. Furthermore, after the 2-year treatment period, 492 of 658 patients (74.8%) qualified for NEDA status (with MRI re-baselined at Week 8 of treatment). The highest rates of NEDA were observed in those who were enrolled due to only MRI activity (80.6%). Those with only relapses had NEDA at a rate of 75.1% and those with both had a rate of 70.5%.

FDA accepted its supplemental biologics license

 application for a version of ocrelizumab with a shorter administration time for the treatment of relapsing and primary progressive MS. The sNDA was accepted by the FDA based on 

 study, a double-blind, prospective substudy to the open-label, single-arm, phase 3b ENSEMBLE (NCT03085810) trial.

 of ocrelizumab in January, reflecting new information about infusion reactions, vaccinations, and risks in specific patient populations.4

1. Weinstock-Guttman B, Bermel R, Cutter G, et al. Ocrelizumab treatment in patients with RRMS who had suboptimal response with one or more prior disease-modifying therapies: CHORDS 2-year results. Presented at MS Virtual 2020 Joint ECTRIMS-ACTRIMS meeting; September 11–13, 2020. Abstract P0221.

2. Wiendl H, Comi G, Oreja-Guevara C, et al. Ocrelizumab Phase IIIb efficacy from CASTING: 2-year NEDA (MRI re-baselined) subgroup rates in RRMS patients with a suboptimal response to prior DMTs. Presented at MS Virtual 2020 Joint ECTRIMS-ACTRIMS meeting; September 11–13, 2020. Abstract P0219.

3. US FDA and EMA accept applications for Roche’s OCREVUS (ocrelizumab) shorter 2-hour infusion time [press release]. Basel, Switzerland: Genentech; Published April 20, 2020. Accessed September 21, 2020. globenewswire.com/news-release/2020/04/20/2018330/0/en/US-FDA-and-EMA-accept-applications-for-Roche-s-OCREVUS-ocrelizumab-shorter-2-hour-infusion-time.html

4. Drug Safety-related Labeling Changes (SrLC). US FDA website. January 15, 2020. Accessed September 21, 2020. accessdata.fda.gov/scripts/cder/safetylabelingchanges/index.cfm.

Articles

A study presented at MS Virtual reveals that treatment with ocrelizumab can improve freedom of individual events in patients with relapsing-remitting multiple sclerosis.

Ocrelizumab Shows Benefit in Patients With Relapsing MS and Prior DMT Exposure

, the 8th Joint ECTRIMS-ACTRIMS meeting, September 11–13, 2020, revealed that there are no between group differences 

 in average fatigue severity or fatigue interference 

among persons with progressive multiple sclerosis (MS) or relapsing-remitting MS (RRMS).

Tracy Herring, PhD, senior fellow, Multiple Sclerosis Rehabilitation & Wellness Research Center, University of Washington, who presented the data, noted that “given the similarity between fatigue and its correlates for both progressive and relapsing forms of MS, future research should consider if the interventions that work for fatigue management in people with relapsing forms of MS work similarly for people with progressive forms of MS.”

The study, which included 573 community-dwelling individuals with MS, looked at outcome measures such as fatigue severity and fatigue interference and used T-test and chi-square analyses to compare group differences.

Researchers also used multiple regression analysis to examine the extent to which the association of risk factors with fatigue severity and interference are moderated by MS subtype. They found that longer MS disease duration was associated with lower average fatigue severity (

 <.001) for persons with progressive MS compared to persons with RRMS (

In an effort to identify common demographic risk factors, Herring and colleagues found that having a college degree or higher was associated with higher fatigue interference in persons with progressive MS (

As the investigators previously noted, future studies will confirm whether interventions for patients with progressive MS can be used for those with RRMS. Fatigue increase has been documented as a major symptom that can impact quality of life for those with MS.

Another study presented at MS Virtual 2020 revealed that patients with RRMS who were stratified by high levels of fatigue (RRMS+HF) had 

 compared to those with low fatigue (RRMS+LF) and individuals with MS.

The data showed that the annualized number of outpatient visits, emergency room visits, and hospitalizations were greater for those with RRMS+HF (15.5 [±15.4]; 1.3 [±3.5]; 0.9 [±2.6]) compared to those with RRMS+LF (11.5 [±17.6]; 0.7 [±2.0]; 0.4 [±1.6]) and non-MS (7.4 [±11.3]; 0.5 [±2.5]; 0.4 [±2.8]) groups.

1. Herring T, Alschuler K, Knowles L, et al. Differences in correlates of fatigue between relapsing and progressive forms of multiple sclerosis. Presented at MS Virtual 2020 Joint ECTRIMS-ACTRIMS meeting; September 11–13, 2020. Abstract P1090.

2. Le H, Ken-Opurum J, Maculaitis M, Sheehan J. Comorbidity and economic burdens of fatigue among patients with relapsing-remitting multiple sclerosis in the United States. Presented at: MS Virtual 2020 Joint ACTRIMS-ECTRIMS meeting, September 11–13, 2020. Abstract P0857.

Future research may help better characterize whether fatigue interventions aimed at one patient population may be effective in the other. 

Progressive and Relapsing-Remitting Multiple Sclerosis Share Similar Fatigue Severity

September 21, 2020 marks the global recognition of World Alzheimer’s Day--a day dedicated to the more than 50 million people worldwide impacted by 

The treatment of AD has perplexed the medical world for decades, with many research efforts resulting in futile trials of investigational therapies that were thought to address key pathological features of the degenerative disease. Still, much progress has been made in our understanding of the mechanisms that contribute to this degeneration, and now, one of the most promising therapies that the community has seen currently sits in front of the FDA. 

To shine a light on this progress and what remains to be seen in the management of AD, NeurologyLive has compiled some of the most recent newsworthy research as well as original commentary and interviews with leaders in the field. 

Below you’ll find the latest information on investigational therapies, commentary on the potential of aducanumab, and the latest pipeline developments. 

Improves Multiple Alzheimer Disease Biomarkers in Phase 2b Study

FDA Accepts Aducanumab for Review as Alzheimer Disease Treatment

Alzheimer Disease Treatment Pipeline: Hope is Trending

Aducanumab, which, if approved, will become the first drug to slow clinical decline in AD through its mechanism of selectively targeting forms of amyloid beta, presents a potential disease- and life-altering development. Click the links below to hear perspectives on the topic from thought leaders Marwan Sabbagh, MD, and James Kupiec, MD. 

Aducanumab: A Potentially Landscape-Altering Treatment for Alzheimer

Aducanumab's Unlikely Road to the FDA: Is Approval Imminent?

Alzheimer’s Association International Conference

 (AAIC) also included several research and clinical highlights, including new data on a promising biomarker as well as an updated report on modifiable risk factors that can potentially prevent or delay up to 40% of cases of dementia. 

P-Tau217 May Detect Alzheimer Disease, Brain Amyloidosis, Tauopathy

12 Modifiable Risk Factors to Reduce Dementia Risk

Lastly, we recently sat down with AD clinician researcher Jeffrey Cummings, MD, ScD, who discussed the changing landscape of the therapeutic pipeline for the disease. Listen to the conversation below:

Mind Moment Podcast, Episode 14: Trends in the Alzheimer Disease Clinical Pipeline

For more of the latest news and expert insights on Alzheimer disease and dementia, visit our Alzheimer disease and dementia 

In honor of World Alzheimer’s Day, NeurologyLive is sharing some of the latest clinical developments and thoughts from leaders in the field.

World Alzheimer’s Day 2020: The Latest News and Commentary on the Treatment of Alzheimer Disease 

Interim analysis from an open-label extension of patients with relapsing forms of multiple sclerosis (RMS) enrolled in the DAYBREAK study (NCT02576717) showed an association between ozanimod (Zeposia; Bristol Myers Squibb) and low annualized relapse rate (ARR) and low counts of new or enlarging T2 and gadolinium-enhancing (GdE) lesions over time.

, the 8th Joint ECTRIMS-ACTRIMS meeting, September 11–13, 2020, senior author Bruce Cree, clinical research director, UCSF Multiple Sclerosis Center, and professor of clinical neurology, USCF Weill Institute for Neurosciences, and colleagues aimed to characterize the long-term safety and efficacy of ozanimod in patients with RMS in this ongoing open-label extension trial.

At Months 24 and 36, 79% and 75% of participants, respectively, were relapse free. A cohort of 2492 participants with a mean ozanimod exposure of 35.4 months (range, 0.03–50.2) revealed an adjusted ARR of 0.112 (95% CI, 0.093–0.135).

Participants within the trial were eligible if they had completed any phase 1, 2, or 3 trial of ozanimod previously. Investigators calculated number of new/enlarging T2 and GdE magnetic resonance imaging (MRI) brain lesions for the subset of patients who entered the open-label extension from an active-controlled phase 3 trial.

Regardless of parent-trial treatment group mean number of new/enlarging T2 lesions per scan at 24 hours was similar (range, 1.57–1.90), as well as the mean number of GdE lesions at month 24 (range, 0.2–0.4). Confirmed disability progression (CDP) was observed in 10.8% and 8.6% of participants at 3- and 6-months, respectively.

READ MORE: Disability, Economic Burden Greater in MS Patients With High Levels of Fatigue

Available data on safety measures from 2039 participants showed that 81.8% of the population had a treatment-emergent adverse event (TEAE). Additionally, 9.5% of patients had a serious TEAE (SAE) and 56 (2.2%) discontinued due to a TEAE. Researchers also noted that similar rates of TEAEs and SAEs occurred when assessed by the parent-trial treatment group.

Nasopharyngitis (17.9%), headache (14%), upper respiratory tract infection (9.9%), and lymphopenia (9.6%) were among the most common TEAEs observed within the extension period. There were no serious opportunistic infections and exposure-adjusted incidence rates of TEAEs and SAEs decreased over time.

Ozanimod, an oral sphingosine 1-phosphate (S1P) receptor modulator was 

 for the treatment of adults with RMS, including clinically isolated syndrome, relapsing-remitting MS, and active secondary progressive MS in March.

The approval of ozanimod was based off data from the phase 3 SUNBEAM (NCT02294058) and RADIANCE part B (NCT01628393) trials that included more than 2600 adults. The randomized, active-controlled studies compared ozanimod to interferon beta-1a (IFNß1a; Avonex) on the primary end point of ARR.

Bristol Myers Squibb announced the commercial launch and 

 in June, making it the first and only S1P on the market that required no first dose observation.

1. Selmaj K, Steinman L, Comi G, et al. Long-term safety and efficacy of ozanimod in relapsing multiple sclerosis in DAYBREAK: an open-label extension study of ozanimod phase 1–3 trials. Presented at MS Virtual 2020 Joint ECTRIMS-ACTRIMS meeting; September 11–13, 2020. Abstract P0217.

2. U.S. Food and Drug Administration Approves Bristol Myers Squibb’s ZEPOSIA® (ozanimod), a New Oral Treatment for Relapsing Forms of Multiple Sclerosis [news release]. Briston Myers Squibb Company. March 26, 2020. finance.yahoo.com/news/u-food-drug-administration-approves-103000096.html

3. Bristol Myers Squibb Announces Commercial Launch and Availability of ZEPOSIA® (ozanimod), a New Oral Treatment for Relapsing Forms of Multiple Sclerosis [news release]. Princeton, NJ; Published June 1, 2020. Accessed June 8, 2020. news.bms.com/press-release/corporatefinancial-news/bristol-myers-squibb-announces-commercial-launch-and-availabil

Along with being generally well tolerated, ozanimod was able to help most patients become relapse free without disability progression.

Author | Marco Meglio

Articles

Ocrelizumab Shows Benefit in Patients With Relapsing MS and Prior DMT Exposure

Progressive and Relapsing-Remitting Multiple Sclerosis Share Similar Fatigue Severity

World Alzheimer’s Day 2020: The Latest News and Commentary on the Treatment of Alzheimer Disease

Ozanimod Shows Long-Term Safety, Efficacy in Open-Label Extension