74
Accreditation and Acknowledgement
§ Forefront Collaborative designates this live activity for a maximum of 1.0 AMA PRA Category 1 Credit™; physicians should claim only the credit commensurate with the extent of their participation in the activity
§ Forefront Collaborative is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians
§ The activity is provided by Forefront Collaborative and supported by an educational grant from Lilly
Faculty Disclosures§ In compliance with ACCME and AMA guidelines, faculty disclosures will be
acknowledged prior to his or her slide presentation
§ When providing information, in whole or in part, related to non-FDA approved uses for drug products and/or devices, the presenter will clearly acknowledge the unlabeled indications or the investigative nature of their proposed uses to the audience
§ Acknowledgement of unapproved uses or the investigational nature of therapies is noted within the slide presentation
Planner DisclosuresEducational activities provided by Forefront Collaborative must demonstrate balance, independence, and scientific rigor. All those in a position to control the content of an activity must disclose all relevant financial relationship(s) with commercial interest(s). For this educational activity, all conflicts of interest have been resolved through peer review and revisions to ensure independence, evidence base, fair balance, and absence of commercial bias. The reviewers of this activity have no relevant financial relationships to disclose.
The following individuals have indicated that neither they nor their spouses/partners have had, in the past 12 months, financial relationship(s) with commercial interests relative to the content of this CME activity:§ Planner (Forefront Collaborative): Katie Detzler
Planner Disclosures (cont.)The following individuals have disclosed that they and/or their spouse/partner has had a financial relationship in the past 12 months:§ Planner (Forefront Collaborative): Lily Zurkovsky, PhD, has personal stock in Teva
Pharmaceutical Industries § Planner: Stewart Tepper, MD, has received salary from Dartmouth-Hitchcock Medical Center and from the
American Headache Society and royalties from Springer; he has been a consultant or on an advisory board for Acorda Therapeutics, Alder BioPharmaceuticals, Alexza Pharmaceuticals, Allergan, AlphaSights, Amgen, Autonomic Technologies, Axsome Therapeutics, Cefaly, Charleston Laboratories, DeepBench, Dr. Reddy’s Laboratories, electroCore, Eli Lilly and Company, eNeura, GLG Pharma, Guidepoint Global, Magellan Rx Management, Neurolief, Nordic BioTech, Novartis, Pfizer, Scion NeuroStim, Slingshot Insights, Supernus Pharmaceuticals, Teva Pharmaceutical Industries, and Zosano Pharma Corporation; Dr. Tepper has contracted research for Alder BioPharmaceuticals, Allergan, Amgen, Autonomic Technologies, Dr. Reddy’s Laboratories, electroCore, eNeura, Neurolief, Novartis, Scion NeuroStim, Teva Pharmaceutical Industries, and Zosano Pharma Corporation; he has ownership interest in Autonomic Technologies
Planner Disclosures (cont.)The following individuals have disclosed that they and/or their spouse/partner has had a financial
relationship in the past 12 months:
§ Reviewer: Deborah Friedman, MD, has been a consultant or on an advisory board for Alder
BioPharmaceuticals, Allergan, Amgen, Biohaven Pharmaceuticals, electroCore, Promius, Supernus
Pharmaceuticals, Teva Pharmaceutical Industries, and Zosano Pharma Corporation; she has been a
speaker for Allergan, Amgen, electroCore, Supernus, Autonomic Technologies, and Teva Pharmaceutical
Industries; she has received clinical trial grant support from, Axon Optics, Autonomic Technologies, Eli Lilly
and Company, Merck, and Zosano Pharma Corporation
§ Reviewer: Lawrence Newman, MD, has contracted research for Alder BioPharmaceuticals, Allergan,
Amgen, Eli Lilly and Company, and Teva Pharmaceutical Industries
§ Reviewer: Todd Schwedt, MD, has consulted or been on an advisory board for Alder BioPharmaceuticals,
Allergan, Amgen, Cipla, Eli Lilly and Company, Ipsen, Dr. Reddy’s Laboratories, Novartis, and Teva
Pharmaceutical Industries; Dr. Schwedt has contracted research for Amgen; he has ownership interest in
Aural Analytics, Nocira, and Second Opinion
How to Claim Credit§ To claim CME credit, you will have to complete the evaluation form located at
your seat and return the program to a staff member at the end of this activity § Please write in (last page) if you are claiming AOA credit
Claiming AOA credit
How to Claim Credit (cont.)§ The pre- and posttest are also located at your seat. If you have not completed
the pretest, please do so now § There will be some time at the end of the activity for you to complete the posttest
Slides and Question Cards§ The slides presented during this symposium can be downloaded at forefrontcollabactivities.com/RethinkingMigraine
§ Question cards are in the center of your table; they will be collected throughout the presentation § The question and answer session will begin following the last presentation § Please hand the question cards to a staff member as they walk around the room
§ As a courtesy to others, please silence your cell phones or set them to vibrate
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Rashmi Halker Singh, MD, FAHS
OVERVIEWThe New Era of Migraine Treatment
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Migraine Pathophysiology
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Summary of Pathophysiology and Targets
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The Small Molecule CGRP Receptor Antagonists: Gepant SummaryAcute Treatment of Episodic Migraine (EM)§ There have been 6 gepants tested which demonstrated efficacy in acute
migraine treatment: olcegepant, BI 44370 TA, telcagepant, MK-3207, rimegepant, and ubrogepant
§ BI 44370 TA, telcagepant, and MK-3207 are all reportedly liver toxic§ Ubrogepant and rimegepant have reported out positive regulatory trials
and will likely be submitted to the FDA for acute treatment of migraine over the next year
§ 2-hour pain freedom ≈ 20% in phase 3 trials§ They do not cause vasoconstriction; unlike triptans, should be safe with
vascular disease1. Tfelt-Hansen P. Headache. 2011;51:118-123. 2. Tfelt-Hansen P, Do TP. Abstract PO-01-48 presented at IHC 2017; Vancouver. 3. Allergan press release. February 6, 2018. https://www.allergan.com/news/news/thomson-reuters/allergan-announces-positive-top-line-phase-3-resul. Accessed April 26, 2018. 4. Biohaven press release. March 26, 2018. http://biohavenpharma.com/biohaven-announces-successful-achievement-of-both-co-primary-regulatory-endpoints-in-two-pivotal-phase-3-trials-of-rimegepant-an-oral-cgrp-receptor-antagonist-for-the-acute-treatment-of-migraine/. Accessed April 26, 2018.
The Small Molecule CGRP Receptor Antagonists: Gepant Summary (cont.)Preventive Treatment of EM§ Atogepant vs placebo reported positive phase 2 trial data in 2018 and showed
drops in mean monthly migraine days for EM; will proceed to phase 3 trials§ No signal of liver toxicity§ Rimegepant will be tested for prevention in phase 2
1. Tfelt-Hansen P. Headache. 2011;51:118-123. 2. Tfelt-Hansen P, Do TP. Abstract PO-01-48 presented at IHC 2017; Vancouver. 3. Allergan press release. February 6, 2018. https://www.allergan.com/news/news/thomson-reuters/allergan-announces-positive-top-line-phase-3-resul. Accessed April 26, 2018. 4. Biohaven press release. March 26, 2018. http://biohavenpharma.com/biohaven-announces-successful-achievement-of-both-co-primary-regulatory-endpoints-in-two-pivotal-phase-3-trials-of-rimegepant-an-oral-cgrp-receptor-antagonist-for-the-acute-treatment-of-migraine/. Accessed April 26, 2018.
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New Outcome Measures to Evaluate Migraine Treatment Effectiveness
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§ Effectiveness in patients with lack of response to previous preventive medications§ Prospective placebo-controlled randomized clinical trials of 2-4 previous
preventives (erenumab LIBERTY trial and fremanezumab FOCUS study) § Subanalyses (erenumab, fremanezumab, galcanezumab)§ Specific exposures: fremanezumab and patients with a lack of success
with onabotulinumtoxinA and topiramate
Clinically Meaningful Outcome Measures
1. Tepper SJ. Headache 2018;58 (suppl3):238-275. 2. Tepper SJ. Headache 2018;58 (suppl3):276-290. 3. https://www.tevapharm.com/news/teva_announces_positive_topline_phase_iiib_results_with_fremanezumab_in_adults_with_migraine_who_did_not_respond_to_multiple_classes_of_preventive_treatments_12_18.aspx. Accessed December 24, 2018. Ï
§ Overall responder rates§ 41% of patients showed ≥75% responder rates of reduction in mean
monthly migraine days at 1 year in the erenumab open-label extension trial§ 54% showed ≥75% responder rates of reduction in mean monthly migraine
days at 1 year in the eptinezumab placebo-controlled RCT§ The ≥75% responder rates are linked to marked drops in disability and
impact and improvements in quality of life in clinical trial data
1. Tepper SJ. Headache 2018;58 (suppl3):238-275. 2. Tepper SJ. Headache 2018;58 (suppl3):276-290. 3. https://www.tevapharm.com/news/teva_announces_positive_topline_phase_iiib_results_with_fremanezumab_in_adults_with_migraine_who_did_not_respond_to_multiple_classes_of_preventive_treatments_12_18.aspx. Accessed December 24, 2018. Ï
Clinically Meaningful Outcome Measures (cont.)
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Options: Classification of Migraine Preventive Therapies AAN AHS Guidelines, 2012
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Considerations for Next Steps
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Considerations for Next Steps (cont.)
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What Is Her Diagnosis? !"#$%&'$()*+,-.(/'"0(.10()'2,0'"30,+(/'4(*0)(+1'5(.3,6.'760)
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What Is Her Diagnosis? (cont.) !"#$%&'$()*+,-.(/'"0(.10()'2,0'314(/).(,+'56107-1'#1)4)/81
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What Is the Evidence for Efficacy of Chronic Migraine Prevention?! !"#$#%&$#%'%()!*%+,%-+./$&0&-#%,+$%)1%.$#2#3-/+34%*"#%"&*%&5$#&67%-$/#6%/-%83*899#**,8557
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What About a Taper?! !"#$%&'(#)*#)*""*+#,+%-#.#/*.'"/#0".1(2%31"#,%+#"/30#2."3*1"#"%#'%$*+#/*+#.4&"*#-*(34."3%1#31".5*6#*02*43.''7#839*1#/*+#8.0"+%31"*0"31.'#+305#,+%-#"/*#::;0
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What About Acute Medication for This Patient?! !"#$%&'()&*+#,-+$%.&(+&/0123$&+#&'$4"#"(56+(%'"("(7&6+-4+8()$&*+#&'68%,&%#,'%-,(%
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Conclusions on the Cases! !"#$%&&'&"()"(*%$"+*','-./,'"0'1/#%./(-&"%*'"2/1'$3"4&'1")/*&.")(*"+*','-./(-"()"567"%-./1'+*'&&%-.&8"%-./93+'*.'-&/,'&8"%-1":5;&
! <-$3",%$+*(%.'8".(+/*%0%.'8"+*(+*%-($($8"%-1"./0($($"%*'"=;:>%++*(,'1")(*"+*','-./(-"()"56
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! <-$3".(+/*%0%.' 9%&"*%-1(0/C'1"#(-.*($$'1"1%.%")(*"4&'"/-"D68"%-1"/.&"'))/#%#3"/-"D6"/&"0(1'&.
! <-%@(.4$/-40.(E/-:8"'*'-40%@8")*'0%-'C40%@8"%-1"A%$#%-'C40%@ 9%,'"'))/#%#3"/-"+*','-./-A"D68"@4."(-%@(.4$/-40.(E/-: /&"-(."=;:>%++*(,'1")(*"+*','-./-A"568"29/$'".9'"6:F&"%*'"=;:>%++*(,'1")(*"'/.9'*"56"(*"D6
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