TA919/Scope Consultation Comments
Page 1

Summary form

National Institute for Health and Care Excellence

Single Technology Appraisal (STA)

Rimegepant for treating or preventing migraine [ID1539]

Response to consultee and commentator comments on the draft remit and draft scope (pre-referral)

Please note: Comments received in the course of consultations carried out by NICE are published in the interests of openness and transparency, and to promote understanding of how recommendations are developed. The comments are published as a record of the submissions that NICE has received, and are not endorsed by NICE, its officers or advisory committees.

Comment 1: the draft remit

Section Consultee/
Commentator		 Comments [sic] Action
Wording Abbvie Yes, the wording of the remit reflects the issues of clinical and cost-
effectiveness about the technology that NICE should consider.		 Comment noted. No
changes to the draft
scope required.
British
Association for
the Study of
Headache
(BASH)		 [Does the wording of the remit reflect the issue(s) of clinical and cost
effectiveness about this technology or technologies that NICE should
consider?] Yes		 Comment noted. No
changes to the draft
scope required.
Biohaven
(manufacturer)		 We suggest that the wording of the remit should be revised to reflect ‘The
clinical and cost effectiveness issues pertaining to the comprehensive
management of migraine across the continuum of migraine care with
rimegepant’.		 Comment noted. The
current wording of the
remit in the draft scope
covers both acute and
preventative migraine
treatment. No changes

National Institute for Health and Care Excellence

Consultation comments on the draft remit and draft scope for the technology appraisal of Rimegepant for treating or preventing migraine [ID1539] Issue date: September 2021

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Summary form

Section Consultee/
Commentator		 Comments [sic] Action
to the draft scope
required.
Novartis We consider the proposed wording of the remit appropriate. Comment noted. No
changes to the draft
scope required.
Teva The wording appears appropriate Comment noted. No
changes to the draft
scope required.
The Migraine
Trust		 [Does the wording of the remit reflect the issue(s) of clinical and cost
effectiveness about this technology or technologies that NICE should
consider?] Yes		 Comment noted. No
changes to the draft
scope required.
Association of
British
Neurologists		 [Does the wording of the remit reflect the issue(s) of clinical and cost
effectiveness about this technology or technologies that NICE should
consider?] Yes		 Comment noted. No
changes to the draft
scope required.
Timing Issues Abbvie Routine Comment noted. No
changes to the draft
scope required.
British
Association for
the Study of
Headache
(BASH)		 Migraine affects 15% of the general population and 2-5% are affected on a
daily basis with significant disability and absenteeism causing direct cost to
the NHS and indirect cost to the economy in general. There are available
treatments, although adverse effects and contraindications due to co-
morbidities leave a significant number of patients with limited or no choice.
Any new treatments to relieve this painful condition are always welcomed as
soon as possible.		 Comment noted. No
changes to the draft
scope required.

National Institute for Health and Care Excellence

Page 2 of 30 Consultation comments on the draft remit and draft scope for the technology appraisal of Rimegepant for treating or preventing migraine [ID1539] Issue date: September 2021

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Section Consultee/
Commentator		 Comments [sic] Action
Biohaven
(manufacturer)		 The timing of the appraisal is completely appropriate given the significant
unmet need with regard to the acute treatment of migraine, the decades-long
lack of novel acute therapies for migraine treatment, and deficiencies related
to both traditional and novel treatments for the prevention of migraine,
described in response to the background section below.		 Comment noted. No
changes to the draft
scope required.
Novartis No comments. N/A
Teva A number of other anti-calcitonin gene-related peptide (CGRP) drugs have
recently been made available in the NHS.		 Comment noted. No
changes to the draft
scope required.
The Migraine
Trust		 We would say there is an urgency to this appraisal (within 2021) as many
people do not have appropriate acute treatment for migraine. This is due to
lack of effects, side effects, potential medication overuse headache from
current treatments or medical comorbidities that exclude current acute
treatments.		 Comment noted. No
changes to the draft
scope required.
Association of
British
Neurologists		 Migraine represents a huge burden to the UK population in terms of morbidity
and days lost to employment		 Comment noted. No
changes to the draft
scope required.

Comment 2: the draft scope

Section Consultee/
Commentator		 Comments [sic] Action
Background
information		 Abbvie Mostly accurate and complete. Comment noted. The
background section is
intended to provide a
brief overview of the

National Institute for Health and Care Excellence

Consultation comments on the draft remit and draft scope for the technology appraisal of Rimegepant for treating or preventing migraine [ID1539] Issue date: September 2021

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Section Consultee/
Commentator		 Comments [sic] Action
Prevalence data from 2003 could be possibly updated with more recent data,
if available.
“…preventive drug treatments have failed..” – needs clarity if these drugs
could belong to same class/category.		 disease and its
management. No
changes to the draft
scope required.
British
Association for
the Study of
Headache
(BASH)		 The information provided is accurate and includes all the relevant facts of the
impact of migraine.		 Comment noted. No
changes to the draft
scope required.
Biohaven
(manufacturer)		 The information does not address the significant unmet need in migraine
patients that cannot tolerate, respond or are ineligible to receive the current
standard of care.The most commonly used migraine specific medication class
for acute treatment are triptans. For many patients triptan treatments are not
adequate or lose efficacy over time, have intolerable side effects, or
cardiovascular contraindications. Among the population with
contraindications, patients have no approved options, and resort to the
persistent use of medications, such as barbiturates and opioids that have the
potential for misuse/abuse. There is recognition among both practitioners and
patients/advocacy that frequent use of acute medications can lead to
medication overuse headaches, a serious condition often requiring intensive
medical management.
With regard to prevention, novel available biologic therapies (CGRP
antagonist -monoclonal antibodies) do ameliorate the severity of migraine by
reducing migraine frequency which is beneficial relative to the traditional oral
preventatives. However, these newer agents are associated with high rates of
discontinuation, due to attenuation of effect, immunogenicity issues, and		 Comments noted. The
background section is
intended to provide a
brief overview of the
disease and its
management. No
changes to the draft
scope required.

National Institute for Health and Care Excellence

Consultation comments on the draft remit and draft scope for the technology appraisal of Rimegepant for treating or preventing migraine [ID1539] Issue date: September 2021

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Section Consultee/
Commentator		 Comments [sic] Action
concerns for women of childbearing potential given biologic ½ lives of 5
weeks. In contrast with the injectable CGRP biologics, rimegepant 75 mg
ODT offers a novel convenient oral medication for the comprehensive
management of migraine, requiring no injection, and with a relatively short
half-life (approximately 11 hours) that allows immediate cessation of therapy
in the event of pregnancy, hypersensitivity reaction, or serious adverse event
(SAE). The rapid onset of effect with rimegepant differentiates it from
injectable biologics and older therapies. An oral agent such as rimegepant
with comparable efficacy to the biologics in terms of migraine frequency
reduction offers a better alternative to patients for whom biologic
preventatives are indicated.
Novartis The wording of the ICHD-3 definition of chronic migraine is “Headache occurring on
15 or more days/month_for more than 3 months_, which, on at least 8 days/month, has
the features of migraine headache” [italicised emphasis added]. The draft scope
description omits this italicised wording. As this wording relating to “more than 3
months” is also included in the NICE recommendation wording for fremanezumab as
an option for preventing chronic migraine [TA631], it is important to ensure the full
ICHD-3 definition of chronic migraine is accurately reported.
The NICE recommendation for both erenumab [TA682] and galcanezumab
[TA659] is described as relating to “adults who experience 4 or more
migraines per month”. This is inaccurate, as the recommendation refers to
adults who experience 4 or more migraine**days** per month.		 Comments noted. The
draft scope background
and comparator
sections has been
updated to state
migraine days to reflect
NICE recommendations
for erenumab and
galcanezumab.
Teva No comment N/A
The Migraine
Trust		 The background information is accurate and complete. Comment noted. No
changes to the draft
scope required.

National Institute for Health and Care Excellence

Consultation comments on the draft remit and draft scope for the technology appraisal of Rimegepant for treating or preventing migraine [ID1539] Issue date: September 2021

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Section Consultee/
Commentator		 Comments [sic] Action
Association of
British
Neurologists		 Yes: although there are existing acute and preventative treatments for
migraine many patients have inadequate response to these, treatments may
be contraindicated because of co-morbidities and patients may not tolerate
side effects		 Comment noted. No
changes to the draft
scope required.
The technology/
intervention		 Abbvie Yes, the description of the technology is accurate, however, the addition of
following will make it more informative.
“Rimegepant is administered orally….” – the information will be more
complete with the frequency of administration.
“.. adults who have 4 to 18 migraine attacks of moderate to severe intensity
per month” – the trial population appears to cover a broader spectrum of
patients. At the appraisal stage, an important consideration will be how and/or
what proportion of trial patients meet the definitions used for the approved
listed comparators, including more specifically, the chronic migraine definition
per ICHD-3 (≥15 Migraine Headache Days); consistently used for the NICE
approved MAbs and botulinum toxin.		 Comment noted. The
technology/intervention
section of the scope is
intended to give a brief
description of the
technology and the trial
populations it has been
studied in. No changes
to the draft scope
required.
British
Association for
the Study of
Headache
(BASH)		 Yes. Rimegepant has been studied both as acute and preventive therapy for
episodic (EM) and chronic migraine (CM).
The preventive study (Croop et al, Lancet 2021) only studied patients with 4-
18 days of headaches per month, although a large number of CM sufferers
have > 20 days of headaches per month and represent significant proportion
of CM sufferers who were excluded from the trial.
Existing preventive treatment was allowed to continue (excluding CGRP
monoclonal antibodies), although those who had failed to respond to>2		 Comments noted. The
committee will consider
the evidence submitted.
No changes to the draft
scope required.

National Institute for Health and Care Excellence

Consultation comments on the draft remit and draft scope for the technology appraisal of Rimegepant for treating or preventing migraine [ID1539] Issue date: September 2021

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Section Consultee/
Commentator		 Comments [sic] Action
preventives were excluded, suggesting the trial did not include a truly
refractory population.
Biohaven
(manufacturer)		 We believe the description provided does not acknowledge that the novel
function of rimegepant to serve as both an acute and preventive migraine
treatment transcends the exclusive categories or classes of existing migraine
treatments that are defined as either acute OR preventive treatment.
If approved, rimegepant will provide for the comprehensive management of
migraine (i.e., both acute treatment and prevention of migraine regardless of
baseline frequency of attacks) with a simple single dose that does not require
patients to engage in polypharmacy for treatment of their migraines. The
formulation (oral dispersible tablet), the single dose (75mg), and the flexible
regimen, provide for effective treatment of acute migraine across 21 efficacy
measures (seen in BHV3000-303), and confer additional benefits such as
migraine frequency reduction, and HRQOL benefits seen in both the open
label long term safety study (BHV3000-201) and the placebo controlled
prevention study (BHV3000-305).		 Comment noted. The
technology/intervention
section of the scope is
intended to give a brief
description of the
technology and the trial
populations it has been
studied in. No changes
to the draft scope
required.
Novartis No comments N/A
Teva No comments N/A
The Migraine
Trust		 [Is the description of the technology or technologies accurate?] Yes Comment noted. No
changes to the draft
scope required.
Association of
British
Neurologists		 Rimegepant inhibits the action of calcitonin gene related peptide: CGRP is
known to be involved in the neural pathways that generate migraine attacks,
but not otherwise thought to be involved in transmission of signals that can
cause severe pain.		 Comments noted. The
committee will consider
the evidence submitted.

National Institute for Health and Care Excellence

Consultation comments on the draft remit and draft scope for the technology appraisal of Rimegepant for treating or preventing migraine [ID1539] Issue date: September 2021

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Summary form

Section Consultee/
Commentator		 Comments [sic] Action
The phase 2/3 placebo controlled study looking at Rimegepant for prevention
of migraine (Croop at el Lancet 2021) excluded those with more than 18
headache days per month and those with non-response to more than 2
preventative drug categories		 No changes to the draft
scope required.
Population Abbvie Yes, appropriately defined.
No, separate subgroups are not needed since it is noted that various
subgroups as listed in “other considerations” will be explored, evidence
permitting.		 Comment noted. No
changes to the draft
scope required.
British
Association for
the Study of
Headache
(BASH)		 The disease burden of migraine is related to the number of days of headache
per month, and its severity. Those with EM have <15 days of headache per
month, although patients with 8-14 days (often referred as high frequency
EM) have disease burden similar to CM, in comparison to those with <8
days/month. Similarly, the morbidity is high in those CM sufferers with >20
days of headache/month, particularly those that had failed >2 preventive
treatments.		 Comment noted. No
changes to the draft
scope required.
Biohaven
(manufacturer)		 We feel it important to describe the eligible population in more detail.
Suggest: patients requiring acute or preventive treatment. A relevant sub-
group for acute treatment would be patients who are refractory/intolerant to
triptans or who have a CV contraindication, for whom no approved migraine
treatments are available. In the recent ICER review of novel acute agents,
rimegepant was deemed to be cost effective (at $40,000/QALY gained)
compared to the US equivalent of best alternative care.		 Comment noted. The
population defined in
the scope is kept broad.
If evidence allows,
considerations of acute
and preventative
migraine separately
should be provided.
Relevant subgroups are
highlighted in the“other

National Institute for Health and Care Excellence

Consultation comments on the draft remit and draft scope for the technology appraisal of Rimegepant for treating or preventing migraine [ID1539] Issue date: September 2021

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Section Consultee/
Commentator		 Comments [sic] Action
considerations” section
of the draft scope, if
evidence allows. No
changes to the draft
scope required.
Novartis Yes, the population is appropriate. However, given the differences in
comparators and relevant outcomes between acute migraine and migraine
prevention contexts (see below), it is appropriate to consider these two
contexts within the adult migraine population as separate decision problems.		 Comment noted. The
comparator section of
the draft scope
highlights the different
treatment options
between acute migraine
and migraine
prevention. The “other
considerations” section
of the draft scope
highlights relevant
subgroups, if evidence
allows. No changes to
the draft scope
required.
Teva No comments. N/A
The Migraine
Trust		 Yes, the population is appropriate defined Comment noted. No
changes to the draft
scope required.
Association of
British
Neurologists		 For preventative treatment it is usual to consider episodic and chronic
migraine separately as they represent different disease burdens		 Comment noted. The
comparator section of
the draft scope
highlights the different
treatment options

National Institute for Health and Care Excellence

Consultation comments on the draft remit and draft scope for the technology appraisal of Rimegepant for treating or preventing migraine [ID1539] Issue date: September 2021

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Section Consultee/
Commentator		 Comments [sic] Action
between acute migraine
and migraine
prevention. The “other
considerations” section
of the draft scope
highlights relevant
subgroups, if evidence
allows. No changes to
the draft scope
required.
Comparators Abbvie Yes, these are the standard approved treatments with which the technology
should be compared. However, it will be important to ascertain how the
eligibility criteria of the rimegepant trial compares to those of the comparators,
at the appraisal stage.
The reimbursed indication should be clearly indicated for each of the
comparators as “episodic and chronic” or “chronic”, as applicable. The
definition of both episodic and chronic should be stated upfront.
For erenumab and galcanezumab, “four or more migraines per month” should
be corrected with “four or more migraineheadache daysper month”.
For fremanezumab, chronic migraine should be defined.
For acute treatment, recommendations per the BASH guidelines (2019)2
including simple analgesics, anti-emetics and triptans can be described as best
alternative care.		 Comment noted. The
comparator section of
the draft scope
highlights the different
treatment options
between acute migraine
and migraine
prevention. The “other
considerations” section
of the draft scope
highlights relevant
subgroups, if evidence
allows. The committee
will consider the
evidence submitted.
The draft scope
background and
comparator sections
has been updated to

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Section Consultee/
Commentator		 Comments [sic] Action
state migraine days to
reflect NICE
recommendations for
erenumab and
galcanezumab.
British
Association for
the Study of
Headache
(BASH)		 The inclusion of CGRP monoclonal antibodies and OnabotulinumtoxinA as
comparators for preventive treatment is inappropriate as they are indicated
only following failure of three preventive treatments, and Rimegepant trials
excluded those with failure of >2 preventives. Appropriate preventives to use
as comparators would include amitriptyline, propranolol, topiramate
(recommended in the NICE guidelines), and candesartan (recommended in
BASH and SIGN guidelines).		 Comment noted. The
comparator section of
the draft scope
highlights the
populations for which
these treatments are
comparators. The
committee will consider
the evidence submitted.
No changes to the draft
scope required.
Biohaven
(manufacturer)		 Yes we agree that a relevant comparator is ‘best alternative care’ but should
be defined as ‘patients who are refractory/intolerant to triptans or who have a
CV contraindication, for whom no approved migraine treatments are
available.		 Comment noted. No
changes to the draft
scope required.
Novartis We agree that the comparators are different for the acute migraine and
migraine prevention contexts, and hence these two contexts will require
different decision problems.		 Comment noted. The
draft scope background
and comparator
sections has been
updated to state

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Consultation comments on the draft remit and draft scope for the technology appraisal of Rimegepant for treating or preventing migraine [ID1539] Issue date: September 2021

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Section Consultee/
Commentator		 Comments [sic] Action
We agree with the comparators included in the draft scope for these two
contexts. All treatments listed as comparators in the ‘Comparators’ section of
the draft scope are recommended as acute treatments or preventive
treatments, accordingly, in the British Association for the Study of Headache
(BASH) national headache management guidelines.1
The wording specifying the populations in which erenumab and
galcanezumab are comparators should say “4 or more migraine**days**per
month” [days is currently missing].
1British Association for the Study of Headache (BASH). National Headache Management System for Adults
2019.		 migraine days to reflect
NICE recommendations
for erenumab and
galcanezumab.
Teva No comment N/A
The Migraine
Trust		 Yes, the listed comparators are the standard treatments currently used in the
NHS		 Comment noted. No
changes to the draft
scope required.
Association of
British
Neurologists		 For acute treatment ‘best alternative care’ could reasonably be described as
the combination of a non-oral triptan and NSAID.
For preventative treatment ‘best alternative care’ could reasonably be
described oral preventive treatments (such as topiramate, propranolol,
amitriptyline).
Whist botulinum toxin and CGRP monoclonal antibodies are available as
preventive treatment options, NICE guidelines suggest that these should only
be used for patients who have failed at least 3 other classes of preventative
treatment: the Croop et al 2021 study of preventive treatment with
Rimegepant excluded those with non-response to more than 2 drug		 Comments noted. The
comparator section of
the draft scope
highlights the
populations for which
these treatments are
comparators. The
committee will consider
the evidence submitted.
No changes to the draft
scope required.

National Institute for Health and Care Excellence

Consultation comments on the draft remit and draft scope for the technology appraisal of Rimegepant for treating or preventing migraine [ID1539] Issue date: September 2021

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Section Consultee/
Commentator		 Comments [sic] Action
categories and therefore a comparison with botulinum toxin an CGRP mabs
is not reasonable in this context.
Outcomes Abbvie Yes. It is understood that only the top-line outcome measures are listed in the
scoping doc. and that the details (sub-groups) will be added in the full scope.
For e.g. frequency of migraine headache days per month is listed as an
outcome measure in the scoping doc but further details such as 50%
responder rate for episodic and 30% for chronic migraine are missing. It is
recommended that the outcome measures closely align to identified/listed
comparator to facilitate robust comparison. Example and recommendations of
additional outcome measures are listed below:
•
percentage of patients with episodic migraine with ≥50% reduction
from baseline in mean monthly MHDs
•
percentage of patients with chronic migraine with ≥30% reduction from
baseline in mean
•
change from baseline in the mean number of migraine days per month
over the entire double-blind treatment phase (Weeks 1 to 12)
change from baseline in the mean number of migraine days per month in the
first 4 weeks (Weeks 1 to 4) of the double-blind treatment phase.		 Comments noted. The
committee will consider
the relevant outcome
measures. No changes
to the draft scope
required.
British
Association for
the Study of
Headache
(BASH)		 We agree the outcome measures suggested by NICE, although not all of
them were used as outcomes in the Rimegepant studies.
The acute Rimegepant study (Croop et al, Lancet 2019), used a 2 hour
response for pain and the most bothersome symptom.		 Comment noted. No
changes to the draft
scope required.

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Section Consultee/
Commentator		 Comments [sic] Action
The preventive treatment trial (Croop et al, Lancet 2021) measured headache
and migraine days, use of rescue medication, MSQ and MIDAS (health
related quality of life measures).
Biohaven
(manufacturer)		 We agree with the list of outcomes measures but these should be described
as one single listing pertaining to the comprehensive treatment of migraine.
Further, given the corroboration of migraine frequency reduction seen in
BHV3000-201 by an observed similar result in BHV3000-305, we maintain
that this outcome pertains to the total treatment eligible population.
We further recommend, that given the debilitating nature of migraine across
its continuum, consideration should be given to indirect burden, such as
measures of absenteeism/presenteeism, in work, school or leisure activities
of daily living. We recently reported that 22% of migraine patients experience
30 days of absenteeism/presenteeism over 3 months.		 Comments noted. The
draft scope highlights
that outcomes and
comparator treatments
vary between acute
migraine and migraine
preventive treatments.
The committee will
consider the evidence
presented.The NICE
methods guideoutlines
the relevant
considerations in an
appraisal. In section
5.1.10, it states that
“Productivity costs are
not included in either
the reference-case or
non-reference-case
_analyses”._No changes
to the draft scope
required.
Novartis We agree with the draft scope that the relevant outcomes differ for the acute
migraine and migraine prevention contexts.		 Comments noted. The
committee will consider

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Section Consultee/
Commentator		 Comments [sic] Action
For migraine prevention, the outcome of response rate should be included, as
defined by a ≥30% reduction in monthly migraine days (MMDs) and a ≥50%
reduction in MMDs for chronic migraine and episodic migraine populations,
respectively. As part of the erenumab appraisal [TA682] it was concluded that
a 30% reduction in migraine frequency is considered a clinically meaningful
response to treatment in chronic migraine, and a 50% reduction is considered
a clinically meaningful response in episodic migraine. This same conclusion
was reached by the appraisal committees for the fremanezumab [TA631] and
galcanezumab [TA659] appraisals. As a clinically meaningful outcome, this
should be included for the assessment of migraine prevention.		 the relevant outcome
measures. No changes
to the draft scope
required.
Teva No comment N/A
The Migraine
Trust		 Yes, the outcomes are appropriate and relevant for the technology appraisal. Comment noted. No
changes to the draft
scope required.
Association of
British
Neurologists		 Yes: a combination of overall health related quality of life and a measure of
reduction in migraine symptoms (e.g. 2 and 24 hrs pain freedom post-dose)
should be used.		 Comment noted. No
changes to the draft
scope required.
Economic
analysis		 Abbvie Since migraine is a long-term condition, a time horizon of 25 years should be
sufficiently long to capture costs and outcomes associated with the disease.		 Comment noted. The
committee will consider
the relevant time
horizons in the
appraisal. No changes
to the draft scope
required.

National Institute for Health and Care Excellence

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Section Consultee/
Commentator		 Comments [sic] Action
British
Association for
the Study of
Headache
(BASH)		 There should be a separate time horizon for cost effectiveness related to
acute and preventive treatment. A longer time horizon is used for preventive
therapy considering natural history of the disease.		 Comment noted. The
committee will consider
the relevant time
horizons in the
appraisal. No changes
to the draft scope
required.
Biohaven
(manufacturer)		 We maintain that the time horizon for the economic analysis should be
sufficiently long to capture the total value of rimegepant treatment (i.e.,
including migraine frequency, reduction associated with repeated effective
acute treatment, and the anticipated amelioration of medication overuse
headache).
The recent ICER Evidence Review concluded that “For adults with moderate-
severe migraine attacks patients for whom triptans are not effective, not
tolerated, or are contraindicated, rimegepant cost effectiveness ratios fell
below commonly cited thresholds for cost-effectiveness (i.e., $50,000-
$150,000/QALY gained ) at an estimated net price that conferred a Cost
Effectiveness ratio of $39,800/QALY gained”. These cost effectiveness ratios
thus anticipate a favorable finding for rimegepant in this base-case given
consistent model designs (i.e., between ICER and NICE).
We further recommend consideration of an integrated cost-effectiveness
model that captures the continuum of care (i.e., acute treatment benefits,
long-term benefits of repeated effective acute treatment (e.g., migraine
frequency reduction, HRQOL improvements and associated health state
utility increments), and the cumulative benefit of same on the progressive
severity of migraine in the prevention population.		 Comments noted. No
changes to the draft
scope required.
Novartis No comments N/A

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Section Consultee/
Commentator		 Comments [sic] Action
Teva A lifetime time horizon was preferred in recent appraisals of migraine drugs
(TAs: 631, 659 and 682), although how this was defined differed. Careful
consideration should be given to the definition of ‘lifetime’.		 Comment noted. The
committee will consider
the relevant time
horizons in the
appraisal. No changes
to the draft scope
required.
Association of
British
Neurologists		 The time horizon for the economic analysis of migraine treatments is difficult
to estimate as migraine incidence may fluctuate widely during an individual’s
lifetime, but a 5-10 year time horizon may be appropriate for preventative
treatment, There should be a separate time horizon for cost effectiveness
related to acute and preventive treatment.		 Comment noted. The
committee will consider
the relevant time
horizons in the
appraisal. No changes
to the draft scope
required.
Equality and
Diversity		 Abbvie The proposed scope and remit do not exclude any people protected by the
equality legislation, lead to a recommendation that has a different impact on
people protected by equality legislation than on the wider population or lead
to recommendations that have an adverse impact on people with a particular
disability or disabilities.		 Comment noted. No
changes to the draft
scope required.
British
Association for
the Study of
Headache
(BASH)		 The disease affects women nearly three times more than men.
Migraine is more common in age group 18-45.		 Comments noted. The
committee will consider
the relevant equalities
issues in this appraisal.
No changes to the draft
scope required.

National Institute for Health and Care Excellence

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Biohaven
(manufacturer)		 We feel that the intended indication for rimegepant, i.e., for the
comprehensive management of migraine in adults, including prophylaxis of
migraine and acute treatment of migraine with or without aura), does assure
equality among the treatment eligible population. Migraine is an exceedingly
disabling condition, particularly among people in the general population, and
while in their most productive years. Impact to quality of life, and work-loss
productivity are seen even in the early stages of the disease, leading to loss
of employment and health care resource utilization (ER and office visits,
medication overuse headache, and opioid dependence.
Lastly, we feel that our recommendations with regard to the proposed remit
and scope, coupled with our intended comprehensive indication, do assure
equality of treatment for all patients		 Comment noted. No
changes to the draft
scope required.
Novartis No comments. N/A
Teva No comment N/A
Association of
British
Neurologists		 No concerns Comment noted. No
changes to the draft
scope required.
Other
considerations		 Abbvie None. N/A
British
Association for
the Study of
Headache
(BASH)		 Medication overuse is seen in up to two-thirds of patients with CM. It is
unclear from the Rimegepant preventive study if those with medication
overuse were excluded from the study.		 Comment noted. The
appraisal committee will
consider the available
evidence. No changes
to the draft scope
required.

National Institute for Health and Care Excellence

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Biohaven
(manufacturer)		 We agree with the subpopulations so defined in this section, and would
recommend that these not be considered as additional issues, but relegated
to the base-case consideration for assessment of the cost-effectiveness of
Rimegepant.		 Comment noted. If
evidence allows,
considerations of acute
and preventative
migraine separately
should be provided. The
subgroups identified in
the “other
considerations” section
have been highlighted
as relevant and can be
considered if evidence
allows. No changes to
the draft scope
required.
Novartis We agree with the relevance of the subgroups proposed for migraine
prevention. Two of the relevant comparators for migraine prevention
(fremanezumab [TA631]; botulinum toxin [TA260]) are only recommended by
NICE for use in chronic migraine (i.e. excluding episodic migraine) and
several of the treatments listed in the ‘Comparators’ section for migraine
prevention are recommended only after at least 3 preventive drug treatments
have failed. Therefore, subgroup analyses by chronic/episodic migraine and
by number of previous preventive treatment failures are appropriate.		 Comment noted. No
changes to the draft
scope required.
Teva No comment N/A
The Migraine
Trust		 It would be helpful to identify any potential drug interactions or medications to
avoid when using this treatment. For example, can it be used with other acute
treatments, how many attacks do you need to treat before efficacy is
assessed.		 Comments noted. This
information should be
included in the
summary of product

National Institute for Health and Care Excellence

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Section Consultee/
Commentator		 Comments [sic] Action
characteristics for this
technology when
available. No changes
to the draft scope
required.
Association of
British
Neurologists		 Medication overuse is seen in up to two third of patients with chronic
migraine. It is unclear from the Rimegepant preventive study if those with
medication overuse were excluded from the study.		 Comment noted. The
appraisal committee will
consider the available
evidence. No changes
to the draft scope
required.
Innovation Abbvie Although various oral preventive treatments are available including
medications from classes such as β-blockers, tricyclic antidepressants,
antiepileptics, and angiotensin receptor antagonists, none are developed
specifically for the treatment of migraine. Low efficacy and poor tolerability
are commonly cited as reasons for failure and discontinuation of migraine
preventive treatments.3
The recently approved CGRP MAbs require subcutaneous administration
every month or every 3 months, which is likely to have compliance
disadvantages. Another important limitation of the MAbs is the need for low
temperature storage conditions. Therefore, the development of oral
alternatives can provide a clinically important treatment option within the
CGRP class. The frequency of administration for rimegepant, however, could
be an important compliance associated limiting factor.
Considering the above, it is yet to be seen how Rimegepant’s efficacy
compares to other approved treatments for this indication.		 Thank you for your
comment. The extent to
which the technology
may be innovative will
be considered in any
appraisal of the
technology. No changes
to the draft scope
required.

National Institute for Health and Care Excellence

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Section Consultee/
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[Do you consider that the use of the technology can result in any potential
significant and substantial health-related benefits that are unlikely to be
included in the QALY calculation?] No
British
Association for
the Study of
Headache
(BASH)		 Rimegepant is the first ever treatment that is efficacious both as acute and
preventive treatment.
Existing specific acute and preventive migraine treatments targeted at CGRP
(triptans, and CGRP monoclonal antibodies, respectively) are relatively
contraindicated in patients with cardiovascular morbidity, This is not the case
for Rimegepant.
Adverse events with Rimegepant are few and mild, and the discontinuation
rate was only 2%, suggesting excellent tolerability.		 Thank you for your
comment. The extent to
which the technology
may be innovative will
be considered in any
appraisal of the
technology. No changes
to the draft scope
required.
Biohaven
(manufacturer)		 Rimegepant is the first and only migraine treatment that functions asbothan
acute and preventive migraine treatment and able to be utilized aross the
spectrum of disease (regardless of frequency of migraines) and the
continuum of care (acute and preventive treatment).
For the reasons cited above, we do maintain that rimegepant does constitute
a ‘step change’ in the treatment of migraine. The long-term benefit of
repeated effective acute treatment with rimegepant confers benefits such as
migraine frequency reduction, HRQOL and work-loss productivity benefits,
that are likely to alter the course of migraine disease progression (i.e.,
reduced risk for MOH, and transition to chronicity). With regard to patients
who require preventative treatments, rimegepant provides an equally effective
alternative to the biologics, without several of the liabilities of biologic		 Thank you for your
comment. The extent to
which the technology
may be innovative will
be considered in any
appraisal of the
technology. No changes
to the draft scope
required.

National Institute for Health and Care Excellence

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Section Consultee/
Commentator		 Comments [sic] Action
treatment (attenuation of effect, immunogenicity, WOCBP issues such as 5
week ½ life.).
We maintain that the totality of data to be provided to the Appraisal
Committee will illustrate the unique value of rimegepant. In addition to the
registrational trials, data will be provided that illustrates migraine frequency
reduction, HRQOL and work-loss productivity, (all mapped to improvements
in health state utilities, reduced pill burden, and direct health care resource
costs). Further, a series of indirect comparisons (both network meta-
analyses, and matched adjusted indirect comparisons) will illustrate improved
efficacy and tolerability versus triptans, and comparable efficacy with better
tolerability versus the biologic preventative agents.
Novartis For migraine prevention NICE has already recommended three CGRP
inhibitors. For acute migraine treatment, if recommended, rimegepant would
be the first CGRP inhibitor recommended for use in this context.		 Thank you for your
comment. The extent to
which the technology
may be innovative will
be considered in any
appraisal of the
technology. No changes
to the draft scope
required.
Teva In terms of mechanism of action, the technology is of limited innovation, as it
acts in the same manner (CGRP receptor antagonist) as some established
migraine therapies (_e.g._fremanezumab)
The oral form, and implications there of, differentiates this intervention from
existing subcutaneous anti-CGRP drugs in the prevention of migraine
In the acute treatment of migraine, the technology could represent an
alternative for people for whom triptans are contraindicated or not tolerated		 Thank you for your
comment. The extent to
which the technology
may be innovative will
be considered in any
appraisal of the
technology. No changes

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Section Consultee/
Commentator		 Comments [sic] Action
to the draft scope
required.
The Migraine
Trust		 It has the potential to have a substantial positive impact especially to those
currently unable to use triptans or NSAIDs or have no or inadequate benefit
from these.		 Thank you for your
comment. The extent to
which the technology
may be innovative will
be considered in any
appraisal of the
technology. No changes
to the draft scope
required.
Association of
British
Neurologists		 Yes:
Rimegepant is the first ever treatment to be shown to be effective as both an
acute and preventive treatment.
It is particularly relevant to those with cardiovascular co-morbidities in whom
standard migraine treatment with triptans is relatively contraindicated.
For those without cardiovascular co-morbidities, it represents an alternative to
existing acute and preventative treatments which may be ineffective or not
well tolerated: adverse events are few, mild and the discontinuation was only
2% suggesting good tolerability.		 Thank you for your
comment. The extent to
which the technology
may be innovative will
be considered in any
appraisal of the
technology. No changes
to the draft scope
required.
Questions for
consultation		 Abbvie Which treatments are considered to be established clinical practice in
the NHS for acute migraine or preventing migraine?
For acute migraine, the treatments as listed in the BASH guidelines (2019)2
inclusive of simple analgesics (aspirin, diclofenac, ibuprofen, ketoprofen,
naproxen, paracetamol and tolfenamic acid) and anti-emetics (domperidone,		 Comments noted. No
changes to the draft
scope required.

National Institute for Health and Care Excellence

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Section Consultee/
Commentator		 Comments [sic] Action
prochlorperazine and metoclopramide) and triptans (almotriptan, eletriptan,
flovatriptan, naratriptan, sumatriptan and zolmitriptan). For prophylaxis,
galcenezumab, fremanezumab and erenumab are relatively new NICE
approved drugs, although yet to be ascertained if they are accepted clinical
practice. Botulinum toxin (Botox) in chronic migraine is NICE approved since
2012 and is an established and widely-used treatment.
How should best supportive care be defined? Should best supportive
care be considered as a comparator?
Best supportive care should be defined as care/treatment that is made
available as the last resort after the failure of approved treatments and/or in
the absence of approved treatment/s for the indication. In this case, BSC
comprises of treatments used for acute management of migraine using
simple analgesics (i.e. ibuprofen, aspirin or paracetamol), a triptan with or
without paracetamol or non-steroidal anti-inflammatory drugs.
Previous appraisals for CGRP MAbs have treated BSC as a comparator and
this would continue to be relevant where rimegepant were being considered
for patients who had failed on advanced lines of treatment such as other
CGRPs or botulinum toxin. Where CGRPs or botulinum toxin are alternative
treatment options (ie in the space where they have been approved by NICE)
then these, rather than BSC, should be the relevant comparators.
To help NICE prioritise topics for additional adoption support, do you
consider that there will be any barriers to adoption of this technology
into practice? If yes, please describe briefly.
Experience suggests that issues with NHS capacity stemming from factors
such as the UK’s relatively low number of neurologists and scarcity of

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Section Consultee/
Commentator		 Comments [sic] Action
headache specialists can act as an adoption barrier for advance lines of
migraine treatment.
Biohaven
(manufacturer)		 All questions pertaining to the consultation have been addressed. We further
concur and support NICE’s decision to conduct a Single Technology
Appraisal for rimegepant. We fully endorse the STA process and intend to
cooperate with NICE with regard to addressing supportive data requirements
as needed. We reiterate our last recommendation that an integrated cost
effectiveness model be developed to fully capture the unique benefits of
rimegepant across the continuum of migraine care.		 Comment noted. No
changes to the draft
scope required.
Novartis How should best supportive care be defined? Should best supportive care be
considered as a comparator?
In the migraine prevention context, recent NICE technology appraisal
guidance for recommended migraine prevention treatments (erenumab
[TA682], fremanezumab [TA631] and galcanezumab [TA659]) has referred to
best supportive care (BSC) as “treatment for migraine symptoms”. The
relevance of BSC as a comparator in the migraine prevention context
depends on where the rimegepant manufacturer positions rimegepant relative
to currently recommended treatment options. For example, if rimegepant is
positioned for use after failure of all other recommended treatment options for
migraine prevention that are detailed in the ‘Comparators’ section of the draft
scope then BSC would be a relevant and appropriate comparator.
Are the subgroups suggested in ‘other considerations appropriate? Are there
any other subgroups of people in whom rimegepant is expected to be more
clinically effective and cost effective or other groups that should be examined
separately?		 Comment noted. No
changes to the draft
scope required.

National Institute for Health and Care Excellence

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Section Consultee/
Commentator		 Comments [sic] Action
Please see our comment on subgroups in the ‘Other considerations’ section
above.
Where do you consider Rimegepant will fit into the existing NICE pathway
Headaches?
Pending the outcome of appraisal for the acute migraine context against the
comparators outlined in the draft scope, we would envisage that rimegepant
would fit within the “Acute treatment” section of the “Management of migraine
(with or without aura)” part of the NICE Headaches pathway.
Separately, pending the outcome of appraisal for the migraine prevention
context against the comparators outlined in the draft scope, we would
envisage that rimegepant would additionally fit within the “Prophylactic
treatment” section of the “Management of migraine (with or without aura)” part
of the NICE Headaches pathway.
NICE intends to appraise this technology through its Single Technology
Appraisal (STA) Process. We welcome comments on the appropriateness of
appraising this topic through this process.
We consider an STA to be the appropriate NICE assessment route.
Teva Have all relevant comparators for rimegepant been included in the
scope?
No comment
Which treatments are considered to be established clinical practice in
the NHS for acute migraine or preventing migraine?		 Comment noted. No
changes to the draft
scope required.

National Institute for Health and Care Excellence

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Section Consultee/
Commentator		 Comments [sic] Action
All of the treatments described in the scope should be considered as
established clinical practice. Guidance for fremanezumab (TA631) was
published 03 June 2020, so this treatment can be considered established
clinical practice in the NHS for preventing migraine for the purposes of this
appraisal.
How should best supportive care be defined? Should best supportive
care be considered as a comparator?
Best supportive care should be defined and considered as in the previous
appraisals.
Are the outcomes listed appropriate?
No comment.
Are the subgroups suggested in ‘other considerations appropriate? Are
there any other subgroups of people in whom rimegepant is expected to
be more clinically effective and cost effective or other groups that
should be examined separately?
•
Would rimegepant be used in combination with existing
treatments for the prevention of migraine?
•
If used for the prevention of migraines, would additional
treatment be used in event of acute migraine or would treatment
continue with rimegepant?
•
Would rimegepant be used in combination with existing
treatments for acute migraine attacks?
No comment.

National Institute for Health and Care Excellence

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Section Consultee/
Commentator		 Comments [sic] Action
Where do you consider rimegepant will fit into the existing NICE
pathway,Headaches?
This will ultimately depend on its cost-effectiveness.
As an acute treatment, it could be an alternative for people for whom triptans
are contraindicated or not tolerated.
As a preventive treatment, it could be an option for people who have failed
several previous lines of treatment.
The Migraine
Trust		 •
How should best supportive care be defined? Should best
supportive care be considered as a comparator?
Best supportive care usually refers to treatment for the migraine symptoms
which is appropriate. It should be considered a comparator.
•
Are the subgroups suggested in ‘other considerations
appropriate? Are there any other subgroups of people in whom
rimegepant is expected to be more clinically effective and cost
effective or other groups that should be examined separately?
Yes, the subgroups suggested are appropriate.
•
Would rimegepant be used in combination with existing
treatments for the prevention of migraine?
This is generally explored in practice or at a later stage. Usually the
preference is to take as few medications as needed, however, it’s something
that could potentially be useful for some people (if supported by evidence of
effectiveness and safety).
•
If used for the prevention of migraines, would additional
treatment be used in event of acute migraine or would treatment
continue with rimegepant?
This is something that may become clearer when it is used in practice or at a
later stage. There may be factors that influence this likelihood that we are		 Comment noted. The
committee will consider
the evidence submitted.
No changes to the draft
scope required.

National Institute for Health and Care Excellence

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Section Consultee/
Commentator		 Comments [sic] Action
currently unaware of. It may also be something that needs to be evaluated on
an individual basis, for example, if triptans are safe and tolerable they may be
a preferred acute option for quicker relief, alongside rimegepant as a
preventive treatment (in a similar way to current treatment management).
•
Would rimegepant be used in combination with existing
treatments for acute migraine attacks?
This is generally explored in practice or at a later stage. Usually the
preference is to take as few medications as needed, however, it’s something
that could potentially be useful for some people (if supported by evidence of
effectiveness and safety).
•
Where do you consider rimegepant will fit into the existing NICE
pathway,Headaches?
It’s likely to depend on cost, access and long-term safety. However, it could
come after simple analgesics, especially for people who can’t tolerate other
treatment options.
•
To help NICE prioritise topics for additional adoption support, do
you consider that there will be any barriers to adoption of this
technology into practice? If yes, please describe briefly.
A barrier is likely to be point of access. If they are only available via a
specialist that is likely to create issues with access, especially as an acute
treatment option. It would be helpful for GPs (and not only specialists) to be
allowed to prescribe as they are the usual first point of access for an acute
migraine treatment and the long waiting times to see specialists.
Additional
comments		 Novartis The ‘Related NICE recommendations and NICE Pathways’ section of the
draft scope refers to the ‘Headaches (2020) NICE Pathway’. However, the
most recent update of this pathway was in May 2021, so this should be
reflected accordingly.		 Comment noted. The
draft scope has been
updated to include this
correction.

National Institute for Health and Care Excellence

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Section Consultee/
Commentator		 Comments [sic] Action
Teva Any additional comments on the draft scope.
In the section ‘Related NICE recommendations and NICE Pathways’, for
consistency, fremanezumab, erenumab and botulinum toxin A should also
have their review dates stated (or in the case of botulinum toxin A, that it will
be reviewed only if significant new evidence available etc), otherwise delete
for galcanezumab. The link to the botulinum toxin A guidance incorrectly links
to the erenumab guidance.		 Comment noted. The
review dates have been
added to other NICE
technology appraisal
guidance in the draft
scope. The link to the
botulinum toxin type A
guidance has been
corrected.

The following consultees/commentators indicated that they had no comments on the draft remit and/or the draft scope

  • GlaxoSmithKline

National Institute for Health and Care Excellence

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