University of Rochester Medical Center

Author Of 3 Presentations

COVID-19 Late Breaking Abstracts

LB1244 - Manifestations and Impact of the COVID-19 Pandemic in Neuroinflammatory Diseases (ID 2130)

Abstract

Background

We have limited understanding of the risks and impact of COVID-19 in neuroinflammatory diseases (NID) of the central nervous system, particularly among patients receiving disease modifying therapies (DMTs).

Objectives

To report initial results of a planned multi-center year-long prospective study examining the risk and impact of COVID-19 among persons with NID.

Methods

In April 2020, we deployed online questionnaires to individuals in their home environment to assess the prevalence and potential risk factors of COVID-19 symptoms in persons with and without NID.

Results

Our cohort included 1,115 participants (630 NID, 98% MS; 485 reference) as of April 30, 2020. 202 (18%) participants, residing in areas with high COVID-19 case prevalence, met the April 2020 CDC symptom criteria for suspected COVID-19, but only 4% of all participants received testing given testing shortages. Among all participants, those with suspected COVID-19 were younger, more racially diverse, and reported more depression and liver disease. Persons with NID had the same rate of suspected COVID-19 as the reference group. Early changes in disease management included telemedicine visits in 21% and treatment changes in 9% of persons with NID. After adjusting for potential confounders, increasing neurological disability was associated with a greater likelihood of suspected COVID-19 (ORadj=1.45, 1.17-1.84).

Conclusions

Our study of real-time, patient-reported experience during the COVID-19 pandemic complements physician-reported MS case registries that capture an excess of severe cases. Overall, persons with NID seem to have a risk of suspected COVID-19 similar to the reference population.

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Clinical Trials Poster Presentation

P0225 - Phase 3 Study Results Assessing the Efficacy and Safety of ADS-5102 (Amantadine) Extended Release Capsules in MS Patients with Walking Impairment (ID 1919)

Speakers
Presentation Number
P0225
Presentation Topic
Clinical Trials

Abstract

Background

ADS-5102, FDA-approved as Gocovri, to treat dyskinesia in Parkinson’s disease, has a unique PK profile, such that once daily bedtime dosing provides higher amantadine concentrations from morning throughout the day and lower at night. Based on results from a 60-subject, 4-week, Phase-2 study, INROADS was designed to confirm benefit of ADS-5102 on walking in MS patients.

Objectives

To evaluate the efficacy and safety of ADS-5102 (amantadine) extended release capsules in patients with multiple sclerosis with walking impairment.

Methods

INROADS comprised a 4-week placebo run-in, followed by a 12-week double-blind period. Five hundred ninety-four MS patients with walking impairment from the US or Canada enrolled, and 560 were randomized, 1:1:1, to 274 mg ADS-5102 (n=185), 137 mg ADS-5102 (n=187), or placebo (n=186). The primary endpoint was the proportion of responders (≥20% improvement from baseline measured in ft/sec) in timed 25-foot walk [T25FW] at Week 16, comparing 274 mg ADS-5012 versus placebo. Subjects who did not have a Week 16 assessment were counted as non-responders. Additional outcomes included timed up and go test, 2-minute walk test, and MS walking scale-12. Prespecified subgroups, including prior dalfampridine use, were analyzed.

Results

Baseline characteristics were similar across treatment arms, with mean time since diagnosis 15.9 years, median EDSS 6.0, and mean T25FW 12.4 seconds; 52.5% reported prior dalfampridine use. At Week 16, 274 mg ADS-5102 demonstrated a statistically significantly greater response rate, 21.1% (P=.01) than placebo (11.3%); the response rate for 137 mg ADS-5102 was 17.6% (P=.08). For subjects who completed the study, the response rates were 28.3% (P< .001) for 274 mg, and 19.6% (P=.049) for 137 mg, vs. 11.9% for placebo. Response rates were consistent for subjects with (20.0%, 15.9%, vs. 11.0%) and without (22.5%, 19.2%, vs. 11.6%) prior dalfampridine use. The most commonly reported (>5%) adverse events (AEs) were peripheral edema, dry mouth, fall, constipation, UTI, and insomnia; AEs led to study drug discontinuation for 20.5% (274 mg), 6.4% (137 mg) and 3.8% (placebo) of subjects.

Conclusions

INROADS met its primary objective of showing clinically meaningful benefit in MS walking speed for 274 mg ADS-5102. A dose-response was seen for both efficacy and tolerability. AEs were consistent with the known safety profile of amantadine. Results suggest a role for ADS-5102 to improve walking in patients with MS, particularly those who have tried and discontinued dalfampridine.

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Disease Modifying Therapies – Risk Management Poster Presentation

P0285 - Alemtuzumab depletion failure and neutralizing anti-drug antibodies: a case report and call for monitoring (ID 912)

Speakers
Presentation Number
P0285
Presentation Topic
Disease Modifying Therapies – Risk Management

Abstract

Background

Alemtuzumab is a monoclonal antibody that targets CD52 positive T-cells and B-cells, and is used to treat relapsing remitting multiple sclerosis. However, despite humanization and depletion of peripheral T and B cells, alemtuzumab generates the highest frequency of binding and neutralizing antibodies of all humanized antibodies currently in clinical use. In some individuals, antibody neutralization appears to be sufficiently severe to allow disease-breakthrough.

Objectives

The objective of this report is to highlight a need to re-evaluate how we approach and monitor anti-drug antibodies to alemtuzumab during treatment of patients with multiple sclerosis.

Methods

This is a presentation of a case report of a 40 year old woman with a history of MS who was started on alemtuzumab in June 2015.

Results

She had breakthrough disease activity in September 2018, so received her third cycle of alemtuzumab in December 2018. In July 2019 she developed right eye blurry vision and bilateral lower extremity weakness. MRIs demonstrated longitudinally extensive right optic neuritis, 17 enhancing lesions throughout the cerebral hemispheres, corpus callosum, and brainstem, five enhancing cervical cord lesions, and two enhancing thoracic cord lesions. Review of her records revealed that her lymphocytes did not deplete following the third cycle of alemtuzumab. A novel serum assay was performed which demonstrated a very high titer of binding and neutralizing alemtuzumab anti-drug antibodies (>7.7 x 105 Lux) compared to an untreated serum sample (1.22 x 104 Lux).

Conclusions

We concluded that her new lesions were secondary to her multiple sclerosis, unchecked as a result of alemtuzumab depletion failure. We are additionally concerned that depletion failure was secondary to the presence of alemtuzumab neutralizing antibodies. We propose that following lymphocyte counts in the months following treatment should be routine if not imperative, with the goal of monitoring for treatment failure. More pro-actively, it may be appropriate to evaluate for neutralizing antibodies before considering administration of third or fourth cycles of treatment.

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