A Single Dose of Rimegepant 75 mg Provides Pain Relief and Return to Normal Poster … · 2019. 12....
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A Single Dose of Rimegepant 75 mg Provides Pain Relief and Return to Normal Function: Results From 3 Phase 3 Trials Richard B. Lipton, MD 1 ; Stewart Tepper, MD 2 ; Deborah I. Friedman, MD, MPH 3 ; Alexandra Thiry, PhD 4 ; Beth Morris, BS 4 ; Vladimir Coric, MD 4 ; Robert Croop, MD 4 1 Albert Einstein College of Medicine, Bronx, NY; 2 Geisel School of Medicine at Dartmouth, Hanover, NH; 3 UT Southwestern Medical Center, Dallas, TX; 4 Biohaven Pharmaceuticals, Inc., New Haven, CT Poster No. P242LB References: 1. GBD. Lancet Neurol. 2018;17:954-76; 2. Lipton RB et al. Headache. 1999;39:S20-6; 3. Lipton RB et al. Cephalalgia. 2018;38(1 suppl):123-55 (abstract MTIS2018-171); 4. Lipton RB et al. AAN 2019 Emerging Science presentation (Data Blitz #005, Poster #075). Disclosures This study was sponsored by Biohaven Pharmaceuticals. RBL, ST, and DIF have received honoraria and research support from Biohaven Pharmaceuticals; RBL is also a stockholder. AT, BAM, VC, and RC are employed by and own stock/stock options in Biohaven Pharmaceuticals. Zydis is a registered trademark of R.P. Scherer Technologies, Inc. • Migraine is consistently ranked among the most common causes of disability worldwide, 1 and patients with migraine have been shown to consider pain relief and restoration of function among the most important attributes of an acute treatment 2 • Rimegepant is an orally administered small molecule calcitonin gene-related peptide receptor antagonist that has demonstrated efficacy and safety in the acute treatment of migraine in 3 separate Phase 3 clinical trials 3,4 — 2 using oral tablets and 1 with a novel orally disintegrating tablet (ODT) utilizing the Zydis ® fast-dissolve technology; rimegepant ODT demonstrated statistically significant pain relief and return to normal function at 60 minutes and through 48 hours postdose • The objective of this pooled analysis was to compare the efficacy of rimegepant with placebo, as measured by rates of pain relief and freedom from functional disability Objective • Three double-blind, randomized, placebo-controlled, multicenter trials of identical design (Figure 1) were conducted utilizing an oral tablet (Study 301, NCT03235479; Study 302, NCT03237845) and an ODT (Study 303, NCT03461757) Methods Figure 1. Study Design • Subjects used an eDiary to record data from predose through 48 hours postdose • Aged ≥18 years, with ≥1-year history of ICHD-3 beta migraine • Two to 8 moderate or severe monthly migraine attacks; <15 monthly headache days (migraine or nonmigraine) over the last 3 months • Preventive migraine medication dose stable for ≥3 months (if using) Subjects • Coprimary efficacy endpoints: pain freedom at 2 hours postdose and freedom from the most bothersome symptom (MBS) at 2 hours postdose • Secondary endpoints included pain relief and freedom from disability at 2 hours postsdose • Safety assessments: AEs, ECGs, vital signs, physical measurements, routine laboratory tests, including liver function tests Assessments • Efficacy analyses were performed on the modified intent-to-treat population • Efficacy endpoints were evaluated using Cochran-Mantel Haenszel tests and stratified by use of preventive medication; noncompleters were classified as failures • Safety analyses were conducted on enrolled subjects who took any dose of study medication (rimegepant or placebo) Statistical Analysis Introduction Conclusions • Pooled results from 3 Phase 3 clinical trials show that a single dose of rimegepant 75 mg provided effective pain relief and return to normal function • A single dose of rimegepant without the use of rescue medications provided sustained pain relief and sustained normal function from 2 through 48 hours postdose • Tolerability and safety were similar to placebo Results cont. • Rimegepant was well tolerated, as shown in Table 2 • The most common AEs were nausea and urinary tract infection (≤1.5%) • No serious treatment-related AEs were reported • No liver safety concerns were identified Safety Table 2. Pooled On-Study AEs and Liver Function Test Results Results cont. • The pooled analysis found that a single dose of rimegepant 75 mg was more effective than placebo on multiple secondary efficacy endpoints, including: – Freedom from nausea, photophobia, and phonophobia – Sustained pain freedom – Rescue medication use Efficacy Figure 2. Pooled Sustained Pain Relief, 2–24 and 2–48 Hours Postdose • Rimegepant 75 mg was more effective than placebo for pooled sustained pain relief from 2–24 hours and from 2–48 hours postdose (Figure 2) Results • There were 3507 subjects in the 3 trials (rimegepant n=1749, placebo n=1758) • Most subjects (86%) were female; their mean age was around 40 years • The mean history of moderate-severe attacks per month was about 4.6, and the mean duration of untreated attacks was approximately 30 hours • The most common historical MBS was photophobia (57%) • About 15% of subjects were using preventive treatment Subjects Efficacy • In the pooled population (N=3507), efficacy results were consistent with the results in the individual trials • Pooled efficacy results showed that rimegepant was more effective than placebo for the coprimary efficacy endpoints of freedom from pain (20.1% vs 12.2%) and freedom from the MBS (36.4% vs 26.6%) at 2 hours postdose • As shown in Table 1, pooled and individual trial data demonstrated that rimegepant 75 mg was more effective than placebo for: – Pain relief at 2 hours postdose – Functional disability freedom at 2 hours postdose Table 1. Pain Relief and Functional Disability Freedom, 2 Hours Postdose Pain Relief at 2 Hours Functional disability freedom at 2 hours Rimegepant 75 mg Placebo Rimegepant 75 mg Placebo Pooled data a n (%) 1013 (57.9) 771 (43.9) 611 (34.9) 419 (23.8) Risk Difference (95% CI) 14.1 (10.8, 17.3) 11.1 (8.1-14.1) Study 301 (tablet b ) n (%) 304 (56.0) 247 (45.7) 181 (33.3) 118 (21.8) Risk Difference (95% CI) 10.3 (4.4, 16.2) 11.5 (6.2, 16.8) Study 302 (tablet c ) n (%) 312 (58.1) 229 (42.8) 175 (32.6) 125 (23.4) Risk Difference (95% CI) 15.3 (9.4, 21.2) 9.2 (3.9, 14.6) Study 303 (ODT d ) n (%) 397 (59.3) 295 (43.3) 255 (38.1) 176 (25.8) Risk Difference (95% CI) 16.1 (10.8, 21.3) 12.3 (7.4, 17.2) a Rimegepant N=1749, placebo N=1758 b Rimegepant N=543, placebo N=541 c Rimegepant N=537, placebo N=535 d Rimegepant N=669, placebo N=682 Figure 3. Pooled Sustained Normal Function, 2–24 and 2–48 Hours Postdose • Rimegepant 75 mg was more effective than placebo for pooled sustained normal function from 2–24 hours and from 2–48 hours postdose (Figure 3) Rimegepant 75 mg N=1771 n (%) Placebo N=1782 n (%) ≥1 AE 252 (14.2) 209 (11.7) Nausea 26 (1.5) 15 (.8) Urinary tract infection 20 (1.1) 10 (.6) ≥1 treatment-related AE 113 (6.4) 85 (4.8) Serious AEs 3 (.2) 3 (.2) ALT or AST>ULN 48 (2.7) 52 (2.9) >3x ULN 2 (.1) 2 (.1) >5x ULN 1 (.06 a ) 0 >10x ULN 0 0 Total bilirubin >2x ULN 0 0 AE, adverse event; alanine transaminase, ALT; aspartate transaminase, AST; ULN, upper limit of normal a Not drug-related, as determined by the investigator; the subject had newly initiated an exercise regimen (weight lifting), and lab results were consistent with muscle injury; results are also included in >3x category. Categories are not mutually exclusive. American Headache Society 61 st Annual Scientific Meeting | July 11-14, 2019 | Philadelphia, PA To download a copy of this poster, scan QR code. Rimegepant is an investigational new drug, not approved or authorized for marketing in the U.S. or any country for any indication or treatment of any disease or condition. This material is being made available through Biohaven’s Medical Affairs Department.
Transcript of A Single Dose of Rimegepant 75 mg Provides Pain Relief and Return to Normal Poster … · 2019. 12....
A Single Dose of Rimegepant 75 mg Provides Pain Relief and Return to Normal Function: Results From 3 Phase 3 TrialsRichard B. Lipton, MD1; Stewart Tepper, MD2; Deborah I. Friedman, MD, MPH3; Alexandra Thiry, PhD4; Beth Morris, BS4; Vladimir Coric, MD4; Robert Croop, MD41Albert Einstein College of Medicine, Bronx, NY; 2 Geisel School of Medicine at Dartmouth, Hanover, NH; 3 UT Southwestern Medical Center, Dallas, TX; 4 Biohaven Pharmaceuticals, Inc., New Haven, CT
Poster No. P242LB
References: 1. GBD. Lancet Neurol. 2018;17:954-76; 2. Lipton RB et al. Headache. 1999;39:S20-6; 3. Lipton RB et al. Cephalalgia. 2018;38(1 suppl):123-55 (abstract MTIS2018-171); 4. Lipton RB et al. AAN 2019 Emerging Science presentation (Data Blitz #005, Poster #075). Disclosures This study was sponsored by Biohaven Pharmaceuticals. RBL, ST, and DIF have received honoraria and research support from Biohaven Pharmaceuticals; RBL is also a stockholder. AT, BAM, VC, and RC are employed by and own stock/stock options in Biohaven Pharmaceuticals. Zydis is a registered trademark of R.P. Scherer Technologies, Inc.
• Migraine is consistently ranked among the most common causes of disabilityworldwide,1 and patients with migraine have been shown to consider pain relief andrestoration of function among the most important attributes of an acute treatment2
• Rimegepant is an orally administered small molecule calcitonin gene-related peptidereceptor antagonist that has demonstrated efficacy and safety in the acute treatmentof migraine in 3 separate Phase 3 clinical trials3,4 — 2 using oral tablets and 1 with anovel orally disintegrating tablet (ODT) utilizing the Zydis® fast-dissolve technology;rimegepant ODT demonstrated statistically significant pain relief and return to normalfunction at 60 minutes and through 48 hours postdose
• The objective of this pooled analysis was to compare the efficacy of rimegepant withplacebo, as measured by rates of pain relief and freedom from functional disability
Objective
• Three double-blind, randomized, placebo-controlled, multicenter trials of identicaldesign (Figure 1) were conducted utilizing an oral tablet (Study 301, NCT03235479;Study 302, NCT03237845) and an ODT (Study 303, NCT03461757)
Methods
Figure 1. Study Design
• Subjects used an eDiary to record data from predose through 48 hours postdose
• Aged ≥18 years, with ≥1-year history of ICHD-3 beta migraine• Two to 8 moderate or severe monthly migraine attacks; <15 monthly headache days
(migraine or nonmigraine) over the last 3 months• Preventive migraine medication dose stable for ≥3 months (if using)
Subjects
• Coprimary efficacy endpoints: pain freedom at 2 hours postdose and freedom fromthe most bothersome symptom (MBS) at 2 hours postdose
• Secondary endpoints included pain relief and freedom from disability at 2 hours postsdose• Safety assessments: AEs, ECGs, vital signs, physical measurements, routine
laboratory tests, including liver function tests
Assessments
• Efficacy analyses were performed on the modified intent-to-treat population• Efficacy endpoints were evaluated using Cochran-Mantel Haenszel tests and stratified
by use of preventive medication; noncompleters were classified as failures• Safety analyses were conducted on enrolled subjects who took any dose of study
medication (rimegepant or placebo)
Statistical Analysis
Introduction
Conclusions• Pooled results from 3 Phase 3 clinical trials show that a single dose of
rimegepant 75 mg provided effective pain relief and return to normalfunction
• A single dose of rimegepant without the use of rescue medicationsprovided sustained pain relief and sustained normal function from 2through 48 hours postdose
• Tolerability and safety were similar to placebo
Results cont.
• Rimegepant was well tolerated, as shown in Table 2• The most common AEs were nausea and urinary tract infection (≤1.5%)• No serious treatment-related AEs were reported• No liver safety concerns were identified
Safety
Table 2. Pooled On-Study AEs and Liver Function Test Results
Results cont.
• The pooled analysis found that a single dose of rimegepant 75 mg was more effectivethan placebo on multiple secondary efficacy endpoints, including:– Freedom from nausea, photophobia, and phonophobia– Sustained pain freedom– Rescue medication use
Efficacy
Figure 2. Pooled Sustained Pain Relief, 2–24 and 2–48 Hours Postdose
• Rimegepant 75 mg was more effective than placebo for pooled sustained pain relieffrom 2–24 hours and from 2–48 hours postdose (Figure 2)
Results
• There were 3507 subjects in the 3 trials (rimegepant n=1749, placebo n=1758)• Most subjects (86%) were female; their mean age was around 40 years• The mean history of moderate-severe attacks per month was about 4.6, and the
mean duration of untreated attacks was approximately 30 hours• The most common historical MBS was photophobia (57%)• About 15% of subjects were using preventive treatment
Subjects
Efficacy• In the pooled population (N=3507), efficacy results were consistent with the results in
the individual trials• Pooled efficacy results showed that rimegepant was more effective than placebo for
the coprimary efficacy endpoints of freedom from pain (20.1% vs 12.2%) and freedomfrom the MBS (36.4% vs 26.6%) at 2 hours postdose
• As shown in Table 1, pooled and individual trial data demonstrated that rimegepant 75mg was more effective than placebo for:– Pain relief at 2 hours postdose– Functional disability freedom at 2 hours postdose
Table 1. Pain Relief and Functional Disability Freedom, 2 Hours Postdose
Pain Relief at 2 Hours
Functional disability freedom at 2 hours
Rimegepant 75 mg Placebo Rimegepant
75 mg Placebo
Pooled dataa n (%) 1013 (57.9) 771 (43.9) 611 (34.9) 419 (23.8)
Risk Difference(95% CI) 14.1 (10.8, 17.3) 11.1 (8.1-14.1)
Study 301 (tabletb) n (%) 304 (56.0) 247 (45.7) 181 (33.3) 118 (21.8)
Risk Difference(95% CI) 10.3 (4.4, 16.2) 11.5 (6.2, 16.8)
Study 302 (tabletc) n (%) 312 (58.1) 229 (42.8) 175 (32.6) 125 (23.4)
Risk Difference(95% CI) 15.3 (9.4, 21.2) 9.2 (3.9, 14.6)
Study 303 (ODTd) n (%) 397 (59.3) 295 (43.3) 255 (38.1) 176 (25.8)
Risk Difference(95% CI) 16.1 (10.8, 21.3) 12.3 (7.4, 17.2)
aRimegepant N=1749, placebo N=1758bRimegepant N=543, placebo N=541cRimegepant N=537, placebo N=535dRimegepant N=669, placebo N=682
Figure 3. Pooled Sustained Normal Function, 2–24 and 2–48 Hours Postdose
• Rimegepant 75 mg was more effective than placebo for pooled sustained normalfunction from 2–24 hours and from 2–48 hours postdose (Figure 3)
Rimegepant 75 mgN=1771n (%)
PlaceboN=1782n (%)
≥1 AE 252 (14.2) 209 (11.7)
Nausea 26 (1.5) 15 (.8)
Urinary tract infection 20 (1.1) 10 (.6)
≥1 treatment-related AE 113 (6.4) 85 (4.8)
Serious AEs 3 (.2) 3 (.2)
ALT or AST>ULN 48 (2.7) 52 (2.9)
>3x ULN 2 (.1) 2 (.1)
>5x ULN 1 (.06a) 0
>10x ULN 0 0
Total bilirubin >2x ULN 0 0AE, adverse event; alanine transaminase, ALT; aspartate transaminase, AST; ULN, upper limit of normalaNot drug-related, as determined by the investigator; the subject had newly initiated an exercise regimen (weight lifting), and lab results were consistent with muscle injury; results are also included in >3x category. Categories are not mutually exclusive.
American Headache Society 61st Annual Scientific Meeting | July 11-14, 2019 | Philadelphia, PA To download a copy of this poster, scan QR code.
Rimegepant is an investigational new drug, not approved or authorized for marketingin the U.S. or any country for any indication or treatment of any disease or condition.This material is being made available through Biohaven’s Medical Affairs Department.
