The Safety of IMC‑1 in Patients With Fibromyalgia: Phase 2a Study Results
William L. Pridgen,1 Carol Duffy,2 Judy F. Gendreau,3 R. Michael Gendreau4 ¹Tuscaloosa Surgical Associates, P.C., LLC, Tuscaloosa, AL, USA; ²Department of Biological Sciences, University of Alabama, Tuscaloosa, AL, USA ³Gendreau Consulting, LLC, Poway, CA, USA; ⁴Virios Therapeutics, Alpharetta, GA, USA
INTRODUCTION RESULTS CONCLUSIONS
• Fibromyalgia (FM) is a chronic disorder • A total of 143 patients from 12 US sites were enrolled in the Efficacy Outcomes • The most commonly reported TEAEs are summarized in Table 1 • Interestingly, despite the celecoxib component of IMC‑1, • IMC‑1 exhibited an encouraging safety study and randomized to 16 weeks of treatment with IMC‑1 gastrointestinal TEAEs were reported less frequently in the characterized by widespread pain, • Patients treated with IMC‑1 reported significantly greater • No single AE caused discontinuation in multiple patients (n=69) or placebo (n=74) IMC‑1 group (29.0%) than the placebo group (42.5%) (Figure 4) profile, as AEs occurred at a lower 1 reductions in pain versus placebo, as measured by mean change receiving IMC-1 fatigue, and cognitive impairment rate and were less severe in the IMC‑1 – One patient randomized to the placebo group withdrew from baseline to week 16 in NRS 24‑hour recall scores (‑1.1 vs • No deaths were reported; serious AEs were reported in 1 Figure 4. Gastrointestinal Treatment Emergent Adverse Eventsa • Patients often experience inadequate consent after randomization but prior to taking any study drug ‑1.9) (Figure 2) treatment group compared with placebo placebo‑treated patient (breast cancer [unrelated]) and 2 relief with approved FM treatments, and was excluded from the analysis populations 45% • Similarly, significant improvement versus placebo was noted in IMC‑1 treated patients (cellulitis [unrelated], acute myocardial Placebo (n=73) • As shown in Figure 1, the and many discontinue or switch IMC-1 (n=69) • Baseline demographic and clinical characteristics were similar FIQ‑R 7‑day recall scores in patients receiving IMC‑1 treatment infarction [possibly related]) 45% discontinuation rate due to AEs was treatments because of tolerability between treatment groups; most patients were Caucasian (‑0.9 vs ‑2.2) (Figure 2) issues2 Table 1. Treatment Emergent Adverse Event Summary 40% nearly 3‑fold higher in patients receiving (95.8%) and female (93.7%) with a mean age of approximately • IMC‑1 also exhibited consistent improvement versus placebo 49 years 35% placebo compared with patients • It has been hypothesized that the across several FM efficacy treatment outcomes, including 50% Adverse events Placebo (n=73) IMC-1 (n=69) receiving IMC‑1, suggesting that reactivation of viral infections, such as – Patients in the placebo group had mean baseline NRS 24‑hour pain reduction responder analyses, functional assessments, At least one TEAE, n (%) 57 (78.1) 50 (72.5) 30% recall scores of 7.1 compared to 6.5 for patients randomized to fatigue scores, and global health status treatment with IMC‑1 was well‑tolerated herpes simplex virus type 1 (HSV‑1), >4% in either treatment group, n (%) 25% IMC‑1 treatment; mean baseline FIQ‑R 7‑day recall pain scores may contribute to the symptoms Figure 2: Mean Change from Baseline in NRS and FIQ‑R Pain Recall Scores at 16 Headache 10 (13.7) 8 (11.6) were 6.8 in the placebo group and 6.5 in the IMC‑1 group Weeks 20% • In this study, IMC‑1 demonstrated associated with FM and that drugs that Nausea 13 (17.8) 3 (4.3) significant reductions in pain, fatigue,
• More patients in the placebo‑treated group discontinued 15% suppress replication and/or reactivation NRS 24-hour recall FIQ-R 7-day recall Diarrhea 9 (12.3) 3 (4.3) treatment prior to study completion compared with the IMC‑1 0.0 and other symptoms in patients with FM of tissue‑resident herpes virus could treatment group (Figure 1) Urinary tract infection 4 (5.5) 6 (8.7) 10% 3 • These results suggest that IMC‑1 may provide symptom relief Vomiting 5 (6.8) 2 (2.9) 5% • Discontinuation rates due to AEs in the placebo group were -0.5 Constipation 6 (8.2) 0 (0.0) offer a promising and well‑tolerated • An oral, fixed dose combination of nearly 3‑fold higher than the IMC‑1 group (P=.012), and the rate 0% Total Diarr ea BS ausea Abdominal Abdominal omiting of tramadol rescue medication usage for acute pain exacerbations -1.0 Pyrexia 3 (4.1) 3 (4.3) discomfort distention treatment option to relieve pain and famciclovir and celecoxib (IMC‑1) was significantly lower in the IMC‑1 group than in the placebo a demonstrated greater tolerability and TEAE, treatment emergent adverse event. Gastrointestinal TEAEs shown include events that occurred in ≥2% of the IMC‑1 treatment group. other symptoms in patients with FM group (P=.037) (Figure 1) IBS, irritable bowel syndrome; TEAE, treatment emergent adverse event. significantly greater pain reduction -1.5 Figure 3. Incidence of Any Treatment Emergent Adverse Events by Severity compared with placebo in a Phase 2a Figure 1. Discontinuation Rates and Rescue Medication Usage • A slightly higher frequency of TEAEs related to elevated hepatic 3 -2.0 P=.031 proof of concept trial (NCT01850420) 100% ild enzymes was observed for IMC‑1 versus placebo (lactate
45% BaselineLS Mean Change From oderate Placebo (n=73) 41.1% Placebo (n=73) P=.001 References 39.2% 90% Severe dehydrogenase [LDH] increased: 5.8% vs 1.4%; gamma glutamyl 40% IMC-1 (n=69) IMC-1 (n=69) • Given the considerable challenges -2.5 80% 78.1% transpeptidase [GGT] increased: 2.9% vs 0), an unsurprising 35% 72.5% 1. Clauw DJ. Fibromyalgia: a clinical review. JAMA. of treating FM, there is a clear need FIQ‑R, Revised Fibromyalgia Impact Questionnaire; LS, least squares; NRS, numerical rating scale. finding given celecoxib’s known safety profile 70% 16.4% 7.2% for effective medications with better 30% 2014;311(15):1547‑1555. 24.6% 60% • No clinically meaningful changes on hematology or chemistry tolerability profiles to manage its 25% Treatment Emergent Adverse Events 2. Liu Y, Qian C, Yang M. Treatment Patterns 50% 33.3% parameters were noted in either treatment group 20% 17.4% Associated with ACR‑Recommended Medications 16.4% 16.4% • TEAEs were reported by 72.5% of patients treated with IMC‑1 symptoms 40% 42.5% 15% and 78.1% of placebo‑treated patients; overall, reported TEAEs • A small increase from baseline in mean resting systolic blood in the Management of Fibromyalgia in the 30% United States. J Manag Care Spec Pharm. 10% 7.2% pressure was noted in the IMC‑1 treatment group compared with