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Safety and Efficacy of Nabiximols in People with Multiple Sclerosis–Associated Joanne Wagner2 | Jerry S

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Safety and Efficacy of Nabiximols in People with Multiple Sclerosis–Associated Joanne Wagner2 | Jerry S Aliza Ben-Zacharia1 | Joris Berwaerts2 | Daniel Checketts3 | Kate Nichol2 Safety and Efficacy of Nabiximols in People With Multiple Sclerosis–Associated Joanne Wagner2 | Jerry S. Wolinsky4 1Hunter-Bellevue School of Nursing at Hunter College, New York, NY, USA; 2Greenwich Biosciences, Inc., Spasticity: Post Hoc Analyses of a Controlled Enrichment Design Study Carlsbad, CA, USA; 3GW Research Ltd., Cambridge, UK, University of Utah School of Medicine, Salt Lake City, UT, USA; 4McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA Poster # 30131 SUMMARY RESULTS Spasticity NRS Score and Spasm Frequency for Phase B Cohorts During Both Phases During Phase A: AEs Occurring in ≥5% of PwMS Mean average 7-day Mean average 7-day ▪ The mean percent reduction from baseline in average 7-day spasticity Numeric Rating spasticity NRS score spasm frequency Scale (NRS) score was 44% for responders (n=266) vs 3% for nonresponders (n=306) Phase A Phase Bꝉ Responders Nonresponders* SOC + Placebo SOC + Nabiximols Phase A Phase B Phase A Phase B ▪ The most frequently reported AEs were dizziness, somnolence, fatigue, and dry mouth PwMS, n (%) (n=266) (n=306) (n=117) (n=124) 10 NBX 14 NBX With an AE 107 (40) 161 (53) 57 (49) 66 (53) (n=241) (n=241) ▪ The AE profile was generally similar between responders and nonresponders, except for SOC + Placebo (n=117) SOC + Placebo (n=117) Withdrew due to an AE 6 (2) 23 (8) 0 8 (7) 12 No washout washout No increased incidence of dizziness in nonresponders AEs occurring in ≥5% of PwMS 8 SOC + NBX (n=124) washout No SOC + NBX (n=124) Dizziness 26 (10) 54 (18) 0 4 (3) 10 During Phase B: Somnolence 16 (6) 13 (4) 1 (1) 4 (3) Fatigue 13 (5) 21 (7) 1 (1) 6 (5) 6 8 -24% CFB ▪ Nabiximols was well tolerated Dry mouth 10 (4) 14 (5) 1 (1) 4 (3) -33% CFB Vertigo 8 (3) 13 (4) 1 (1) 7 (6) 6 -44% CFB 4 ▪ Nabiximols provided continued benefit relative to Phase A baseline for those randomized Nausea 6 (2) 17 (6) 2 (2) 5 (4) -46% CFB in Phase B to continue treatment with nabiximols UTI 6 (2) 10 (3) 12 (10) 9 (7) p=0.011 4 p=0.006 Muscle spasms n/a n/a 8 (7) 7 (6) 2 Mean spasm frequency Mean spasticity NRS score NRS Mean spasticity ▪ Those who were randomized to placebo in Phase B showed a variable loss of efficacy Diarrhea n/a n/a 6 (5) 3 (2) 2 AE, treatment-emergent adverse event; PwMS, people with multiple sclerosis; SOC, standard of care; UTI, urinary tract infection. *Phase A nonresponders include noncompleters (n=34). 0 0 ꝉAn AE with onset in Phase A was not reported as an AE in Phase B unless its severity increased during Phase B or the AE resolved and then recurred in Phase B. BL 1 2 3 4 BL 1 2 3 4 5 6 7 8 9 10 11 12 BL 1 2 3 4 BL 1 2 3 4 5 6 7 8 9 10 11 12 Time (weeks) Time (weeks) INTRODUCTION Spasticity NRS: Phase A Responders vs Nonresponders Baseline (BL) included a period of 7 days prior to first titration dose. Each datapoint represents average of the prior 7 days. ▪ Nabiximols, an endocannabinoid system modulator, is a complex botanical mixture containing delta-9- All patients on single-blind nabiximols (n=572) CFB, change from Phase A baseline; NBX, nabiximols; NRS, Numerical Rating Scale; SOC, standard of care. 10 Phase A data only pertain to persons randomized to 12 weeks of nabiximols or placebo in Phase B; all persons received nabiximols during Phase A. There was no washout period between Phase A and Phase B. tetrahydrocannabinol, cannabidiol, and other cannabinoid and noncannabinoid components. 9 Phase AA respondersresponder (n=266) (n=266) Phase A nonresponders*nonresponder* (n=306) (n=306) day 8 - ▪ Efficacy of nabiximols in treating spasticity symptoms associated with MS has been demonstrated in 7 1-3 -3% CFB multiple RCTs. 6 5 METHODS ▪ GWSP06042 used an enriched trial design: People with MS (PwMS) were treated with single-blind nabiximols 4 -44% CFB in addition to SOC for 4 weeks in Phase A, and those reporting at least 20% improvement in spasticity NRS 3 score were randomized in Phase B (12 weeks); concomitant medications remained stable throughout both 2 Mean 7 Mean average spasticity NRS score NRS spasticity Phase A SOC + Nabiximols Phase B phases. 1 0 SOC + Placebo SOC + Nabiximols ▪ Prior published analysis from study GWSP06042 reported results as change from Phase B baseline. BL 1 2 3 4 PwMS inadequately Time (weeks) 572 117 124 ▪ The objectives of this post hoc analysis were as follows: BL, baseline; CFB, change from baseline; NRS, Numerical Rating Scale. managed with SOC *Phase A nonresponders include noncompleters. ─ Assess adverse event profile during Phase A for Phase A responders vs Phase A nonresponders ─ Assess efficacy outcomes in Phase A and Phase B relative to Phase A baseline (screening) ▪ Phase A response definition: ≥20% reduction in average 7-day spasticity NRS score at the end of Phase A Study design Single-blind Double-blind (Week 4) relative to baseline. Follow-up time, weeks 4 12 Demographics, Baseline Characteristics, Previous Cannabis Use, and Dose of Study Drug Caregiver Global Impression of Change (CGIC): Phase B Phase A SOC + Nabiximols Phase B Proportion of caregivers reporting improvement on CGIC during Phase B Responder definition ≥20% reduction in spasticity NRS score ≥30% reduction in spasticity NRS score Responders Nonresponders* SOC + Placebo SOC + Nabiximols 90 (n=266) (n=306) (n=117) (n=124) SOC + PBO SOC + NBX 80 Primary endpoint Spasticity NRS score Female sex, n (%) 163 (61) 184 (60) 73 (62) 72 (58) 70 68% CFB Mean age, years 48.2 49.5 48.1 49.1 60 Outcomes assessed Responders vs nonresponders*: Nabiximols vs placebo: Mean duration of MS, years 12.5 12.3 11.8 13.3 50 in this analysis • AEs • AEs 43% CFB MS subtype, n (%) 40 • Spasticity NRS scoreꝉ • Spasticity NRS score Percentage 30 Primary progressive 43 (16) 69 (23) 19 (16) 20 (16) • Spasm frequency (daily spasm count) • Spasm frequency (daily spasm count) 20 • CGIC‡ • CGIC Secondary progressive 125 (47) 155 (51) 58 (50) 62 (50) 10 Relapsing/remitting 94 (35) 73 (24) 37 (32) 41 (33) 0 AE, adverse event; CGIC, Caregiver Global Impression of Change; NRS, numerical Rating Scale; PwMS, people with multiple sclerosis; SOC, standard of care. ꝉ ‡ Progressive relapsing 4 (2) 9 (3) 3 (3) 1 (1) BL Week 4 Week 8 Week 12 *Phase A nonresponders include noncompleters. Scale: 0=no spasticity to 10=worst possible spasticity. CGIC was collected at the end of Phase A. Mean EDSS score 5.9 6.0 5.9 6.0 No washout Mean duration of spasticity, years 7.7 7.4 6.7 8.6 PBO, n 75 72 69 69 ▪ Participants self-titrated during the first 14 days of Phase A, up-titrating through a predefined escalation NBX, n 74 69 66 71 Mean baseline spasticity NRS score 7.0 6.8 7.1 7.0 scheme based on efficacy and tolerability to their individual optimal dose (maximum permitted dose: Median sprays/dayꝉ during study (Q1,Q3) 9.0 (7,10) 9.0 (6,11) 9.0 (7,11) 9.0 (6,10) BL, baseline; CFB, change from Phase B baseline; NBX, nabiximols; PBO, placebo; SOC, standard of care. 12 sprays/day). Sample sizes were reduced as not all participants had a caregiver to make this assessment. EDSS, Expanded Disability Status Scale (0=no disability, 5-9.5=walking impairment, 10=death due to MS); MS, multiple sclerosis; NRS, Numeric Rating Scale (0=no spasticity to ▪ Spasticity NRS minimally clinically important difference (MCID, 18%) and clinically important difference (CID, 10=worst possible spasticity); SOC, standard of care. ▪ Caregivers were asked: How have the person’s general functional abilities changed since Visit 2 ꝉ 4 *Phase A nonresponders include noncompleters (n=34). In Phase B, 20% of placebo cohort vs 11% of nabiximols cohort reached maximum dose of 12 sprays/day. (Phase A baseline)? 30%) have been previously established in PwMS. ▪ Groups were generally similar. ▪ Improvement includes “Minimally Better,” “Much Better,” or “Very Much Better.” Disclosures: First presented at the virtual Joint ACTRIMS-ECTRIMS Meeting, 2020. This study was sponsored by Greenwich Biosciences, Inc. Medical writing and editorial assistance was provided to the authors by Jeanelle Spencer, PhD, and Dena McWain of Ashfield Healthcare Communications, and funded by Greenwich Biosciences, Inc. All authors met the ICMJE authorship criteria and had full To obtain a PDF of this poster: access to relevant data. Neither honoraria nor payments were made for authorship. ABZ and JSW have consulted for, conducted studies funded by, or received honoraria for services provided to GW Pharmaceuticals companies; JB, KN, and JW are employees of Greenwich Biosciences, Inc., and DC is an employee of GW Research Ltd. Nabiximols is a complex botanical mixture containing delta-9- Presented: American Physical Therapy • Scan the QR code or tetrahydrocannabinol, cannabidiol, and other cannabinoid and non-cannabinoid components. Nabiximols is not approved for any indication in the U.S. Nabiximols is approved for symptom improvement in patients with moderate to severe spasticity due to multiple sclerosis who have not responded adequately to other antispasticity medications in >25 countries outside of the U.S.; additional marketing Association Combined Sections Meeting; • https://www.gwqrcodes.com/898694 approval in Israel includes use as adjunctive treatment for the symptomatic relief of neuropathic pain in adults with multiple sclerosis and as adjunctive analgesic treatment in adults with advanced cancer.
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