Single Technology Appraisal

Rimegepant for preventing episodic migraine [ID6275]

Committee Papers

NATIONAL INSTITUTE FOR HEALTH AND CARE EXCELLENCE

SINGLE TECHNOLOGY APPRAISAL

Rimegepant for preventing episodic migraine [ID6275]

Contents:

The following documents are made available to stakeholders:

1. Response to consultee, commentator and public comments on the Appraisal Consultation Document

2. Comments on the Appraisal Consultation Document from Pfizer

3. Consultee and commentator comments on the Appraisal Consultation Document from:

• a. The Migraine Trust

• b. British Association for the Study of the Headache

• c. AbbVie

• d. Teva

4. Comments on the Appraisal Consultation Document received through the NICE website

5. Evidence Review Group critique of company comments on the ACD

6. Technical engagement responses and statements from experts:

• a. Dr Brendan Davies, Consultant Neurologist & Clinical Lead, Midlands Regional Headache clinic, University Hospital of North Midlands – clinical expert nominated by Association of British Neurologists

7. Clinical expert response to questions from NICE technical team from:

• a. Dr David Kernick, GP – clinical expert, nominated by Teva UK Limited

8. Evidence Review Group post-ACM2 response to updated list price

• Any information supplied to NICE which has been marked as confidential, has been redacted. All personal information has also been redacted.

Rimegepant for preventing migraine

Single Technology Appraisal

Response to consultee, commentator and public comments on the Appraisal Consultation Document (ACD)

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Type of stakeholder:

Consultees – Organisations that accept an invitation to participate in the appraisal including the companies, national professional organisations, national patient organisations, the Department of Health and Social Care and the Welsh Government and relevant NHS organisations in England. Consultees can make a submission and participate in the consultation on the appraisal consultation document (ACD; if produced). All non-company consultees can nominate clinical experts and/or patient experts to verbally present their personal views to the Appraisal Committee. Company consultees can also nominate clinical experts. Representatives from NHS England and clinical commissioning groups invited to participate in the appraisal may also attend the Appraisal Committee as NHS commissioning experts. All consultees have the opportunity to consider an appeal against the final recommendations, or report any factual errors, within the final appraisal document (FAD).

Clinical and patient experts and NHS commissioning experts – The Chair of the Appraisal Committee and the NICE project team select clinical experts and patient experts from nominations by consultees and commentators. They attend the Appraisal Committee meeting as individuals to answer questions to help clarify issues about the submitted evidence and to provide their views and experiences of the technology and/or condition. Before they attend the meeting, all experts must either submit a written statement (using a template) or indicate they agree with the submission made by their nominating organisation..

Commentators – Commentators can participate in the consultation on the ACD (if produced), but NICE does not ask them to make any submission for the appraisal. Non-company commentator organisations can nominate clinical experts and patient experts to verbally present their personal views to the Appraisal Committee. Commentator organisations representing relevant comparator technology companies can also nominate clinical experts. These organisations receive the FAD and have opportunity to report any factual errors. These organisations include comparator technology companies, Healthcare Improvement Scotland any relevant National Collaborating Centre (a group commissioned by NICE to develop clinical guidelines), other related research groups where appropriate (for example, the Medical Research Council and National Cancer Research Institute); other groups such as the NHS Confederation, the NHS Commercial Medicines Unit, the Scottish Medicines Consortium, the Medicines and Healthcare Products Regulatory Agency, the Department of Health and Social Care, Social Services and Public Safety for Northern Ireland).

Public – Members of the public have the opportunity to comment on the ACD when it is posted on the Institute’s web site 5 days after it is sent to consultees and commentators. These comments are usually presented to the appraisal committee in full, but NICE reserves the right to summarise and edit comments received during consultations, or not to publish them at all, where in the reasonable opinion of NICE, the comments are voluminous, publication would be unlawful or publication would be otherwise inappropriate.

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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.

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Rimegepant for treating or preventing migraine [ID1539]

Consultation on the appraisal consultation document – deadline for comments 5pm on 14 March 2023. Please submit via NICE Docs.

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Rimegepant for treating or preventing migraine [ID1539]

Consultation on the appraisal consultation document – deadline for comments 5pm on 14 March 2023. Please submit via NICE Docs.

Summary

Pfizer are disappointed that NICE have chosen not to recommend rimegepant for the treatment of acute and preventative migraine following the first Appraisal Committee Meeting (ACM) on January 19[th] , 2023. We strongly agree with the Migraine Trust’s statement released after the publication of the Appraisal Committee Document (ACD), which acknowledges the considerable unmet need that remains in the United Kingdom for people suffering with migraine for whom rimegepant can provide an effective alternative treatment option.[1 ]

The EAG’s preferred 2-year time horizon for the acute model is of particular concern as it underestimates the length of time patients, who require acute treatment, suffer with migraine. It is known migraine is a chronic disease and onset occurs during teenage years and continues until a patient reaches their 40s and 50s. Therefore, it is reasonable to assume patients will require acute treatment over the original base case time horizon of 20-years. Furthermore, a longer time horizon has been supported by clinical experts, study data and real-world evidence (RWE).

The Company have included the Committee’s preferred assumptions in the revised base case and when combined with the lowered list price of rimegepant (from £20.00 to £13.55 per pill), rimegepant is cost-effective under a £20,000 willingness to pay (WTP) threshold, as detailed in Table 2.

Given all the committee’s preferred assumptions have been included, the degree of certainty around the ICER has substantially increased, suggesting a threshold above £20,000 could be considered more appropriate. In addition, the ICER reduces significantly when the positive uncertainties associated with the MMD reduction with acute Rimegepant (ICER <£12,000 per QALY) and the subgroups relevant to the decision problem are included in the model (ICER <£16,000 per QALY) are included.

The committee also requested further exploration of the time horizons via scenario analysis which are also presented in Table 2. However, even with the most extreme scenario with a 2-year time horizon (which can be consider inappropriate given discussion below), the ICER remains below £30,000 per QALY.

The detailed responses to the ACD and the requested information by the committee follow Table 1 overleaf.

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Rimegepant for treating or preventing migraine [ID1539]

Consultation on the appraisal consultation document – deadline for comments 5pm on 14 March 2023. Please submit via NICE Docs.

Please return to: NICE DOCS

Rimegepant for treating or preventing migraine [ID1539]

Consultation on the appraisal consultation document – deadline for comments 5pm on 14 March 2023. Please submit via NICE Docs.

costs in the initial 28-day cycle treatment acquisition cost and subsequent 28-day to the ongoing 28-day cycles. treatment acquisition cost for all treatments (while the exception of the loading dose for galcanezumab). CUTE TE 1 Time Horizon Clinical experts, RWE and study data all suggest a time horizon of >10 years is most appropriate in the acute model of migraine. The ACD states ‘The committee considered both the 2- and 20-year time horizons but concluded that the costs and benefits of rimegepant as an acute treatment should be reflected in a shorter time horizon than 5 years and more explanation is needed to determine the most appropriate length’. We have provided additional evidence, from clinical experts, trial data and RWE that all suggest a time horizon of >10 years is appropriate.

ACUTE TE

Clinical experts

Clinical experts support a time horizon of longer than 10 years to properly capture benefits and cost relating to acute treatment of migraine.

A survey of general practitioners (GPs) based in the United Kingdom indicate a time horizon of 20-years is appropriate to fully capture a patient’s experience with acute migraine and in turn ensure all the associated health outcomes and costs are included in the model.

• The Company conducted a survey of 164 GPs to further understand the appropriate time horizon to be included in the acute model.

• Recipients of the survey were asked ‘Based on your experience and/or clinical judgement, for how many years do you think patients suffer from acute migraine attacks over their lifetime?’.

  • Of the GPs surveyed, 68% responded >5 years, with the largest percentage selecting the >10 years and ≤20-years category.

  • Figure 1, demonstrates a low confidence in a 2-year time horizon, suggested by the EAG, to capture the outcomes and costs for patients requiring acute migraine treatment.

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Rimegepant for treating or preventing migraine [ID1539]

Consultation on the appraisal consultation document – deadline for comments 5pm on 14 March 2023. Please submit via NICE Docs.

Figure 1 GP acute treatment time horizon responses

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Further to the above survey, another survey of 12 neurologists with an interest in headache, supported a time horizon of >10 years for the acute model of rimegepant.

• Recipients of the survey were asked ‘Based on your experience and/or clinical judgement, for how many years do you think patients suffer from acute migraine attacks over their lifetime?’

  • Of the Neurologists surveyed, 83.3% responded >10 years, with the largest percentage (50%) selecting the ≥20-years category.

  • Figure 2, demonstrates no confidence in a 2-year time horizon, suggested by the EAG, to capture the outcomes and costs for patients requiring acute migraine treatment.

Figure 2 Neurologists acute treatment time horizon responses

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Rimegepant for treating or preventing migraine [ID1539]

Consultation on the appraisal consultation document – deadline for comments 5pm on 14 March 2023. Please submit via NICE Docs.

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The ACD states ‘The clinical experts agreed with the EAG that a 2-year time horizon is more appropriate’. Please note Pfizer believes this statement to be factually incorrect as in the public section of the Appraisal Committee Meeting (ACM) one clinical expert, Dr Brendan Davies, Consultant Neurologist and the Clinical lead for Neurology at the University Hospital of North Midlands, agreed with the 20-year time horizon during the discussions on the appropriate time horizon.

Extension study data and extrapolation

In the long term follow up study (BHV3000-201), patients remained on treatment up to 52 weeks with only a small percentage discontinuing (2.7%). The model extrapolates from the long-term study, BHV3000-201, which shows patients remain on treatment at 20-years, suggesting a 20-year time horizon would be most appropriate to capture all relevant cost and QALY impacts.

Trial demographics show disease duration beyond 20 years

The time horizon assumption of 20-years in the Company’s base case acute model is reflective of the disease history of participants enrolled in the clinical studies that is informing the model. Given patients with an average disease history of 20-years had sufficient unmet need to pursue acute migraine medication in clinical trials, this provides sufficient evidence that the need for acute treatments for migraine is long-lasting and thus a 20-year time-horizon is appropriate. In the pivotal clinical trials disease onset was on average 21 years old and average age at enrolment in clinical trials was approximately 39 years of age.

• The trial data is supported by the literature whereby Steiner et al. reported onset of migraine in England being 22 years of age and average age at the time of the study was 43 noting patients were suffering from 26 migraines a year, 20 years after onset of migraine.[2]

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Rimegepant for treating or preventing migraine [ID1539]

Consultation on the appraisal consultation document – deadline for comments 5pm on 14 March 2023. Please submit via NICE Docs.

RWE

Migraine prescription data supports the inclusion of a time horizon longer than 5 years (noting data beyond 5 years was not available). The company conducted a study to understand how long patients with migraine receive prescriptions to better understand the appropriate time horizon to be adopted in the acute model.

• The data analysed was from IQVIA OMOP UK Medical Research Data (IMRD) The Health Improvement Network (THIN). The registry captured 119,918 patients who were newly diagnosed with migraine between January 1[st] , 2010, and September 30[th] , 2017; with prescription data being captured until September 2022.

  • Of the 29,376 patients with more than one triptan prescription during follow-up, 24.30%

    • (7,150) had ≥ 5 years between their first and last triptan prescription on record.

• Using a more stringent approach by defining a ‘treatment line’ as 2 triptans within 12 months of each other, 23,448 (19.6%) of patients had at least 1 treatment line of triptans

  • Of which, 15.7% had ≥5 years between the first and last triptan prescription in their first treatment line (i.e., had a gap of no more than 12 months between triptan prescriptions for 5 or more years continuously), suggesting an unmet need with ineffective or poorly tolerated therapy.

• It is worth noting, some patients may have exhausted all treatment options and given up on treatment i.e., their migraine has not resolved and would still utilise treatment if more were available. While some patients may buy treatments (e.g., triptans) over the counter (OTC) as it is cheaper than prescriptions. Therefore, the above results should be interpreted as conservative estimates of the length of time patients are receiving acute treatment.

Consistency with preventative treatment of the same condition

• The prevention model adopts a lifetime horizon of 20-years; therefore, it could be deemed illogical to propose a different time horizon for the same disease for the acute treatment model.

2

Reduced monthly migraine days

MMD reduction should be included in the acute model. Given the Committee acknowledges ‘there is biological plausibility in the suggestion that taking rimegepant as needed may reduce MMDs’. Removing the MMD reduction experienced by patients taking rimegepant PRN has a significant impact on benefit as demonstrated by the change in incremental QALYs in Table 2 when MMD reduction is included in the model. This strongly contradicts the conclusion in the ACD whereby it states, ‘removing the assumption from the model ‘may be considered as a small, potential uncaptured benefit’. By excluding the reduction in MMDs, the company’s updated base case is highly conservative as reflected by the impact of this positive uncertainty seen in Table 2.

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Rimegepant for treating or preventing migraine [ID1539]

Consultation on the appraisal consultation document – deadline for comments 5pm on 14 March 2023. Please submit via NICE Docs.

3 Revised acute base case and scenario analyses

The Company have included the Committee’s preferred assumptions in the revised base case and when combined with the lowered list price of rimegepant (as noted in the summary above), Rimegepant is costeffective under a £20,000 willingness to pay (WTP) threshold, as detailed in Table 2.

Given all the committee’s preferred assumptions have been included, the degree of certainty around the ICER has substantially increased, suggesting a threshold above £20,000 could be considered more appropriate. In addition, the ICER reduces significantly when the positive uncertainties associated with the MMD reduction with acute Rimegepant (ICER <£12,000 per QALY) and the subgroups relevant to the decision problem are included in the model (ICER <£16,000 per QALY) are included.

The committee also requested further exploration of the time horizons via scenario analysis which are also presented in Table 2. However, even with the most extreme scenario with a 2-year time horizon (which can be consider inappropriate given discussion above), the ICER remains below £30,000 per QALY.

Table 2 Changes to the company’s cost-effectiveness estimate in acute

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Rimegepant for treating or preventing migraine [ID1539]

Consultation on the appraisal consultation document – deadline for comments 5pm on 14 March 2023. Please submit via NICE Docs.

the post hoc subgroup defined treatment failure differently'. Consequently, the Committee requested clarification of the difference between the prespecified and post hoc subgroups.

Data across the three Phase 3 trials (Study BHV3000-303, Study BHV3000-301, Study BHV3000-302) were pooled to facilitate subgroup analyses of patients who had failed ≥2 triptans. The protocols for these trials included a pre-specified subgroup analysis of triptan non-responders, defined as “any subject that failed 2 or more molecular entities for efficacy reasons. To be considered a failure for a molecular entity, the subject must have failed on all routes of administration that the subject tried for the molecular entity.”

A table summarising the details of the pre-specified triptan non-responder is provided below. The number of patients included in the pooled sample using this pre-specified definition was: rimegepant (n=78) and placebo (n=104).

Table 3 summarises the criteria of the pre-specified triptan non-responder definition (i.e. reason for failure, frequency of reason and number of routes of administration that had to be failed).

Given the strict criteria used for pre-specified definition of triptan non-responder resulted in a relatively small sample size that omitted patients who had failed triptans for reasons of intolerability, a post-hoc analysis was performed that modified this definition to include all patients who reported failure of ≥ 2 triptans. This post-hoc analysis included those patients that had failed ≥ 2 previous triptans for reasons of intolerability as well as efficacy. In addition, patients only had to have failed on ≥ 1 route of administration rather than failing on all routes. This increases the clinical relevance of the post-hoc analysis as adverse events are a common reason for patients discontinuing triptan treatment in clinical practice, and patients do

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Rimegepant for treating or preventing migraine [ID1539]

Consultation on the appraisal consultation document – deadline for comments 5pm on 14 March 2023. Please submit via NICE Docs.

Please return to: NICE DOCS

Rimegepant for treating or preventing migraine [ID1539]

Consultation on the appraisal consultation document – deadline for comments 5pm on 14 March 2023. Please submit via NICE Docs.

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----- Start of picture text -----
2 hours post-dose ***** **** ***** * *** *******
Pain relapse from 2 to ******* ******** ****************** *********** ********** *****************
48 hours post-dose **** *** ******** * *********
5 Prespecified subgroup results from the clinical trials BHV3000-301, BHV3000-302,
BHV3000-303, for the population who have had 2 or more triptans that have not worked
Table 5 below presents the prespecified subgroup results alongside the pooled mITT results, which are the
base case in the model. The prespecified subgroup results from studies 301-303, for the population who
have had 2 or more triptan failures is consistent with the post-hoc analysis as previously mentioned,
however please note again the prespecified analysis (in Tables 4 and 5) should be interpreted with caution
as the risk differences as several endpoints are not significant which is likely due to low sample sizes.
Table 5 Primary and secondary endpoint results, pooled mITT analysis and prespecified pooled
analysis who failed ≥2 triptans
Pooled mITT analysis Prespecified pooled analysis of
≥2 triptans
RIM PBO Risk RIM PBO Risk
n/N (%) n/N (%) difference n/N (%) n/N (%) difference
*stratified *stratified (95% CI) (95% CI)
risk risk p value p value
Primary endpoints
Pain freedom at 2 *************** ************ *************** ********** ********* ***************
hours post-dose *** ******* ** **** ********
Freedom from MBS *************** ************ *** ********** ********* ***************
at 2 hours post- **** *************** ** **** ********
dose ***
Secondary endpoints
Pain relief at 2 *************** ************ *************** ********** ********* ***************
hours post-dose * *** ********* ** **** ********
Functional disability *************** ************ *************** ********** ********* ***************
at 2 hours post- * *** ******** ** **** ********
dose
Sustained pain *************** ************ *************** ********** ********* ***************
relief 2 to 24 hours * *** ********* ** **** *********
post-dose
Rescue Medication *************** ************ *************** ********** ********* ***************
Use within 24 hours *** *********** ** **** *********
post-dose
Sustained pain *************** ************ *************** ********** ********* ***************
relief 2 to 48 hours * ** ********* ** **** **********
post-dose
Freedom from *************** ************ *************** ********** ********* ***************
photophobia at 2 *** ********* ** *** *********
hours post-dose
Sustained pain *************** ************ *************** ********** ********* ***************
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Rimegepant for treating or preventing migraine [ID1539]

Consultation on the appraisal consultation document – deadline for comments 5pm on 14 March 2023. Please submit via NICE Docs.

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----- Start of picture text -----
freedom from 2 to ** ****** ** ** *******
24 hours post-dose
Freedom from *************** ************ *************** ********** *********
phonophobia at 2 *** ******* ** ***
hours post-dose
Sustained pain *************** ************ *************** ********** *********
freedom from 2 to * *** ******
48 hours post-dose
Freedom from *************** ************ *************** ********** *********
nausea at 2 hours *** ****** ** ***
post-dose
Pain relapse from 2 *************** ************ *************** ********** *********
to 48 hours post- *** ********* * **
dose
6 Economic analyses using the prespecified subgroup results
Rimegepant remains cost-effective using the prespecified subgroup analysis, and therefore, the Company’s
revised base case is a conservative estimate as demonstrated in Table 2 above. The prespecified
subgroup results show a positive uncertainty given the reduction in the ICERs. Here again, the prespecified
results are similar to that of the post-hoc analysis.
PREVENTION
7 Revised prevention base case
Based on willingness-to-pay (WTP) thresholds of £20,000 or £30,000 per QALY, rimegepant is considered
cost-effective compared to each mAb as the ICERs are above these WTP thresholds and the incremental
net monetary benefits (NMBs) are negative. In the revised base case (Table 6), the monoclonal antibodies
(mAbs) are associated with higher costs and higher QALYs than rimegepant. Please note, the revised base
case includes the committee’s preferred assumption, updated health care resource use (HCRU) costs and
the lower list price noted in Table 1 in the summary above.
Secondary care cost savings
Rimegepant is expected to offer cost savings in terms of HCRU compared to the mAbs for migraine
prevention if predominately managed in primary care, as demonstrated by the total costs presented in
Table 6 below . Please note,
***************************
************
The NHS is transforming rapidly with the imminent implementation of recommendations from the Getting It
Right First Time (GIRFT) Neurology Report 2021. [5] GIRFT has set out a vision of neurological care closer to
home with services provided in a community setting supported by triage systems to empower general
practice with efficient advice and guidance. The recently published National Neuroscience Advisory Group
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Rimegepant for treating or preventing migraine [ID1539]

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(NNAG) headache & facial pain pathway has built on this vision with a template for migraine to be managed in general practice, supported by community-based headache clinics rather than secondary care wherever possible.[6 ]

The Oxfordshire headache pathway has adopted the triage and community headache clinic approach recommended by GIRFT and NNAG with 89% of all headache referrals now triaged away from general neurology, freeing up 979 appointments per annum.[7] The Oxfordshire community clinic approach had benefits beyond freeing up secondary care capacity; prior to their community headache appointment 32% of patients felt able to manage their headache and this rose to 100% after the clinic appointment.

In addition, during discussions with clinical experts, it has come to light that rimegepant can provide cost savings in terms of HCRU for patients in the community. Rimegepant has the unique offering of providing the first CGRP-targeted preventative treatment in primary care for patients with migraine.

Please note, the revised base case has been updated to explore a more primary care centric approach for migraine prevention care using rimegepant. Additional HCRU scenario analysis have also been presented. Table 6 below.

• ************************************************************************************************************. • The revised base case includes a one-off initiation cost and a 3-month follow-up cost, with a GP (£39.23 per visit) for rimegepant and with a neurologist (£194.24 per visit) for the comparator mAbs.[8,9] Additionally, a one-off neurologist referral cost has been added to the mAbs costed as one GP visit (£39.23).[8] We believe this to be a conservative approach as monitoring care will likely continue in primary care for rimegepant and secondary for mAbs.

• • Consequently, a scenario analysis has been provided whereby all rimegepant care (initiation visits, 3-month follow-up and monitoring visits) takes place in primary care for patients using rimegepant.

• Rimegepant can offer cost savings in terms of HCRU compared to the mAbs for migraine prevention if predominately managed in primary care as demonstrated by the total costs presented in Table 6 overleaf.

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Rimegepant for treating or preventing migraine [ID1539]

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Rimegepant for treating or preventing migraine [ID1539]

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References:

1. The Migraine Trust. NICE has rejected migraine medication Rimegepant for use on the NHS in England. 2023 [Available from: https://migrainetrust.org/news/nice-has-rejectedmigraine-medication-rimegepant-for-use-on-the-nhs-in-england/ (Last assessed March 2023).

2. Steiner, T. J., Scher, A. I., Stewart, W. F., Kolodner, K., Liberman, J., & Lipton, R. B. (2003). The prevalence and disability burden of adult migraine in England and their relationships to age, gender and ethnicity. Cephalalgia, 23(7), 519-527.

3. Shamliyan TA, Choi JY, Ramakrishnan R, Miller JB, Wang SY, Taylor FR, et al. Preventive pharmacologic treatments for episodic migraine in adults. J Gen Intern Med. 2013;28(9):1225-37

4. Pfizer. Data on File: CPRD Aurum Analysis. 2022

5. Fuller, G. GIRFT Programme National Specialty Report. 2021. [Available from: https://neurologyacademy.org/articles/girft-report-for-neurology (last assessed March 2023)]

6. National Neuroscience Advisory Group (NNAG). Optimum clinical pathway for adults: Headache & Facial pain. 2023. [Available from: https://static1.squarespace.com/static/5f1021faf6248b39f4c64f5d/t/63dbb10ab1d6657b00 247962/1675342095594/04+NNAG+Headache+and+Facial+Pain+Pathway+Final.pdf (last assessed March 2023)]

7. NICE. Oxfordshire Headache Pathway for the Efficient Diagnostic and Management Support of Headache Disorders.2018. [Available at: https://www.nice.org.uk/sharedlearning/oxfordshire-headache-pathway-for-the-efficientdiagnostic-and-management-support-of-headache-disorders (last assessed March 2023)]

8. Jones K, Burns A. Unit Costs of Health and Social Care Canterbury (Kent), UK: Personal Social Services Research Unit, University of Kent; 2021 [Available from: https://kar.kent.ac.uk/92342/ (last accessed May 2022)

9. NHS Improvement. National Schedule of NHS costs - Year 2019-2020 [Available from: https://www.england.nhs.uk/national-cost-collection/ (last accessed January 2022)

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Rimegepant for treating or preventing migraine [ID1539]

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needs to be better treatments to improve the current care for people with migraine. 4 The hugely disadvantaged When considering the options people have for acute treatment (CG150): Some cannot use a triptan, NSAID or are unable to restrict them to the recommended number of days to avoid medication overuse. These people are overwhelmingly disadvantaged. Moreover, those for whom these acute treatments are contraindicated have no good treatment. Best available care is not an effective option and although we advise against use of opioids in migraine, this may be their only alternative option. Use of opiates will carry its own complications, such as medication overuse headache and dependency, which further compound migraine symptoms and can lead to greater disability for the person with migraine and the subsequent greater use of healthcare resources, including specialist services. Some people use a triptan and have partial relief or side effects, and subsequently cannot treat when needed. Their migraines continue to impact and restrict their work and function. A proportion of these will not consult after a poor response to existing treatments, and resort to self-treatment with OTCs and opioids. 5 Do not ignore the advantages to patients and the NHS As an acute treatment, the oral route of administration of rimegepant gives control back to the patient, who can treat early and appropriately to get the best relief. As an oral treatment with good tolerability, it could provide an excellent opportunity for patients to receive the treatment in the primary care setting, even if it had to be initiated in secondary care in the early stages. In addition to treating acute attacks, this could reduce the number of referrals to specialists and associated costs and waiting times. A treatment that is migraine-targeted without complications of medication overuse headache and is well tolerated should be approved in our view, to meet the treatment need for this disadvantaged group of people for whom the currently recommended triptans and NSAIDs are not an option. We consider it unconscionable to deny this group a treatment option that is more beneficial than placebo. 6 Preventive Use The ACD states that ‘rimegepant might also reduce MMDs. Lack of comparative long

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Rimegepant for treating or preventing migraine [ID1539]

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term evidence to support this.’

When NICE was reviewing the CGRP mAbs for migraine prevention , we were also advised of the lack of data in long term use and in comparisons with botulinum toxin-A (Botox) in preventing migraine. Fortunately, the CGRP mAbs were approved which has been beneficial to many people.

A priority group for prevention should include the group of people with migraine: who either do not wish to or cannot tolerate an injection treatment, cannot access cgrp mAbs, or may have tried but not found them effective or tolerable.

7

We strongly disagree with the decision to eliminate the option of rimegepant, a migrainespecific (non-repurposed), acute and preventive treatment.

We would urge the committee to reconsider the decision, for a treatment that has the potential to alleviate the disability and negative impact of migraine on people’s mental health, emotional well-being, relationships and function at work, particularly for the disadvantaged groups.

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unlawful or otherwise inappropriate.

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8 Finally, Teva wishes to reiterate that a number of additional trials for rimegepant are reported to be ongoing that would provide data that are highly relevant to this appraisal and would address some of the current uncertainties surrounding this product (BHV3000-407 [NCT05518123], BHV3000-406 [NCT05509400], BHV3000-309 [NCT05399485]). From the publicly available data on clinicatirals.gov, these trials are due for completion in 2024, with interim results perhaps available sooner.

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Rimegepant for treating or preventing migraine [ID1539]

Comments on the ACD received from the public through the NICE Website

Notes N/A Comments on the ACD: Question: Are there any aspects of the recommendations that need particular consideration to ensure we avoid unlawful discrimination against any group of people on the grounds of race, gender, disability, religion or belief, sexual orientation, age, gender reassignment, pregnancy and maternity?

Response: I can only submit a general response to the decision taken on Rimegepant, based on my experience of suffering frequent migraine throughout my adult life. I am 65 years old and take triptans for acute treatment, but with some trepidation, aware of my increasing risk of developing cardiovascular disease given my age. Rimegepant would offer myself and others in my age group a viable alternative without the cardiovascular contraindications that triptans have. Therefore I would request that NICE rexamine this decision

Question: Are there any aspects of the recommendations that need particular consideration to ensure we avoid unlawful discrimination against any group of people on the grounds of race, gender, disability, religion or belief, sexual orientation, age, gender reassignment, pregnancy and maternity? Response: Discriminates against chronic heath issues. This drug could help so many people who without it have an incredibly poor quality of life. This is a last resort for many people, and even with the unknown long term issues this would at least allow people to have a better quality of life

Name XXXXXXXXXXXXXX Organisation N/A Conflict N/A Comments on the ACD:

As a lifelong migraine sufferer who was forced into early retirement by Medication Overuse Headaches caused by “soldiering on” through headaches, trying to earn a living. Now, after 2 years of Botox treatment and a year of Ajovy, I have started to get my life back. With fewer ant generally milder headache days a month, I am able to make plans for the first time in many years.

I still need to take triptans 8 times a month, mostly with a second dose.

As I am 65 this year the triptan option will become progressively more risky. Rimegepant and the other gpant medicines are my only hope of continued recovery. I have been following the progress of these medicines in the US and waiting for them to become available in the UK.

I plead with you to reconsider your decision and make Rimegepant available where triptans are not appropriate.

Name XXXXXXXX Organisation N/A Conflict N/A Comments on the ACD:

Comments on Section 1 Recommendations, 1.1:

This is a huge disappointment for people who have not found an effective treatment for migraine control, particularly those who cannot take triptans because of age or other health issues, such as high blood pressure. like most other migraine treatments, triptans have been adopted by the migraine community from medications initially developed to treat other conditions. it is only relatively recently that specific migraine treatments have become available. Those of us who use triptans regularly do so with a heavy heart because we are well aware of the risks of medicine overuse headache, and we actually

feel acute guilt at taking them, but often have little alternative in trying to live a reasonably balanced life. Gepants would have given us the opportunity to achieve this safely and appropriately and now it seems this opportunity is being denied migraine sufferers. I feel reliance on triptans entrench migraine difficulties, due to their risk of medicine overuse headache and help to create chronic sufferers. every triptan taken increases the need and likelihood of needing to take addition tablets. Gepants do not appear to cause this rebound effect, and as such would be extremely useful for people such as myself who regularly rely on acute medication to manage their symptoms. I feel like I have to beg for everything and am being punished for being ill. Clinicians can sometimes view patients as almost responsible for their condition, when the fact is that their condition has been mismanaged due to inappropriate treatment and lack of options. Now here we have a treatment which again is being denied. Do any of the people making these decisions actually suffer from migraine themselves?

Comments on Section 1 Recommendations, 1.2:

The comment I should like to make here is that the committee were critical of the success rate of Rimegepant in comparison with other injectable drugs, such as fremanezumab. However, I find this galling, and actually irrelevant, because access to these so called superior drugs is also strictly limited and are not freely available. So on the one hand they are being lauded as a more effective treatment, but this hardly matters if the said recommended treatment is also unavailable. For instance, it is not possible to move from one drug to another in this group. If there is a fail in one, for whatever reason {and in my case it was probable antibody reaction, having worked brilliantly initially} it is not possible to try a sister drug. So comparing it with a treatment that in itself is unavailable seems pointless. When are migraine sufferers going to be able to stop feeling like beggars or criminals, simply for being ill? I'm sorry if this is emotive, but when you wake up each day wondering if this is going to be the day that it all becomes too much to bear, with all that might entail, it is difficult to keep things on a purely intellectual level. I'm 67 years old and have been like this for years and years and I'm just looking for a bit of peace before I die.

Question: Are the summaries of clinical and cost effectiveness reasonable interpretations of the evidence? Response: No, not enough data has been collected

Question: Are the recommendations sound and a suitable basis for guidance to the NHS? Response: No, not enough data has been collected

Question: Are there any aspects of the recommendations that need particular consideration to ensure we avoid unlawful discrimination against any group of people on the grounds of race, gender, disability, religion or belief, sexual orientation, age, gender reassignment, pregnancy and maternity? Response: Yes, data should explore the impact for women at different stages of the menstrual cycle

As a member of the public who has suffered from migraine with aura for the past 28 years, a condition that has caused me immense physical and psychological suffering, I am saddened and disappointed by this initial decision.

I feel extremely fortunate to have benefitted from specialist neurology treatment. I am on two daily preventative medications and am fortunate to receive NHS monthly erenumab injections. Migraine attacks are still a significant concern for me, can cause me to be unable to work, and reduce my quality of life.

I was so hoping for another possible preventative medication which might be more effective than those I currently take, easier to administer, and with fewer side effects.

For reasons that are probably unclear to most observers, NICE has taken a different view to regulators in the US and EU. I greatly hope that NICE's concerns will be assuaged in further deliberations and this medication approved.

Question: Are there any aspects of the recommendations that need particular consideration to ensure we avoid unlawful discrimination against any group of people on the grounds of race, gender, disability, religion or belief, sexual orientation, age, gender reassignment, pregnancy and maternity?

Response: The committee seems to acknowledge that migraine has a disproportionate burden on women; but then rather seems to pass over this. Perhaps it should take further into account equality implications of a new medication with an easier means of administration and which allows populations who suffer from cardiovascular disease to be treated.

professionals failed to diagnose my migraine and it was only as a result of a fellow migraineur watching me suffer an attack that this was identified when I was already 64. I am fortunate in that I have been able to access care privately and am on Ajovy, but this is not fully effective so I will be asking my specialist neurologist to add another medication - and following recent studies Rimegepant would be my first choice for this. Please do not sentence us to continuing pain, and especially as we get beyond 65 and are denied triptans and other pain reducers. We will have to resort to OTC medications, are you aware of the risks of long-term use of paracetamol, aspirin etc and do you take these into account in your deliberations? And just the suffering .... please think again. Question: Are the summaries of clinical and cost effectiveness reasonable interpretations of the evidence?

Response: I question the validity of attributing any sort of cost effectiveness to this - why not allow a 3-month trial per patient and, if the drug us found to be effective, allow that patient to continue to be prescribed it? Given that relief from migraine is not guaranteed for any drug for any one person this should enable targeted relief for those of us who suffer from severe chronic pain. How much value do you put on someone's 24x7 misery and the impact that has not only on them and their overall health and quality of life but everyone they come into contact with? My own life has improved significantly with Ajovy, and I hope to be able to reduce my pain (not just a headache by the way) further by trying another drug in combination with it.

Question: Are the recommendations sound and a suitable basis for guidance to the NHS?

Response: No - I do not find them to be sound. Please see my answers to the previous 2 questions. Question: Are there any aspects of the recommendations that need particular consideration to ensure we avoid unlawful discrimination against any group of people on the grounds of race, gender, disability, religion or belief, sexual orientation, age, gender reassignment, pregnancy and maternity?

Response: Yes. One in 5 women have migraine and half of them are not even diagnosed and we are therefore untreated for our pain and other symptoms. Many of them have probably been misdiagnosed - for example as having sinus headaches. What is the cost to society of this, at least some of which must be contributing to the level of long-term sickness? And what is the cost to society? Additionally - older people are routinely denied treatment simply due to our age, and given we now live to perhaps age 85 on average this results in having to suffer 20 years of untreated pain. Please do not assume that migraine gets better with age - while it does for some people for others it does not or even gets worse. And here is a drug that could help, with minimal risks even to older people or those with cardiac

issues, and we don't even want to offer it to see if that individual's life might improve? This is not a morally acceptable approach.

Name XXXXXXXXXXX Organisation N/A Conflict N/A Comments on the ACD: I wonder if any of the evaluation committee are migraine sufferers, like myself who have been trying different migraine treatments since 2019. I have tried at least 3 different oral medications which were not developed specifically for migraines, all of which were unsuccessful, but I had to stay on each of them for 3 months at a time. I also had to withdraw from each of them before I could start afresh. Now we are in 2023, and finally I reached the top if the queue to try Botox injections, which do not work either. I understand I may now, finally, be eligible to try one of the drugs which were actually developed specifically for migraine!!! People like me who cannot work, have a social life, or any quality of life due to chronic migraine, should be at least given a chance to try these drugs. Whatever hope, even slim, is worth having and at the moment, people like me have little. I feel the document did not allow for enough time to be given for this evaluation. Please give people like me a bit of a chance of a decent life. Question: Has all of the relevant evidence been taken into account? Response: No, I do not believe so. Question: Are the summaries of clinical and cost effectiveness reasonable interpretations of the evidence? Response: No, I do not believe so Question: Are the recommendations sound and a suitable basis for guidance to the NHS? Response: No. Use for preventative and acute migraine should certainly be allowed on the NHS for people suffering from medication overuse headaches. Medication overuse headaches are bound to occur when triptans are needed on a frequent basis, and also painkillers, as the triptans do not always work. For people like me, this new drug would be a lifesaver. It would be the only safe alternative to triptans. Question: Are there any aspects of the recommendations that need particular consideration to ensure we avoid unlawful discrimination against any group of people on the grounds of race, gender, disability, religion or belief, sexual orientation, age, gender reassignment, pregnancy and maternity? Response: I believe that being a white female in her fifties means I am frequently discriminated against in favour of other genders, sexual

orientations and nationalities!!! If I was a transgender person I am sure that due to the current rabid political climate, I would be given the new drug!!!!

Name XXXXXXXXXXXXXXXXXX Organisation N/A Conflict N/A Comments on the ACD: I am affected by chronic migraine, and whilst triptans work for me I regularly experience medication overuse headache. This means I have no other acute treatment option to choose from when I am experiencing medication overuse migraines. This drug could help with this. This new treatment option is very much needed. Unlike other acute treatments such as triptans, non-steroidal antiinflammatory drugs (NSAIDs), and other painkillers, the gepants don’t seem to cause rebound headache (medication overuse headache). This is a really important finding and highlights the importance of having this treatment option for medication overuse migraines. When I am experience medication overuse migraines I have to suffer through a full blown attacked to break the cycle which can last for hours and means I miss out of work and life. Comment on section 1.3 (recommendations), “The company's evidence for people who have had 2 or more triptans that have not worked” This does not consider the role of rimegepant in supporting those with medication overuse headaches. Comment on section 3.1 (details of the condition), “he committee concluded that migraine is a debilitating condition that substantially affects both physical, social and psychological aspects of life and employment.” I agree with this statement Comment on section 3.2 (treatment pathway), “he committee concluded that for acute treatment, at least 2 triptans should be tried before another treatment is considered.” this does not consider it's role in medication overuse migraines Comment on section 3.3 (comparators), “Clinical experts agreed that after triptans there are no other treatment options available.” this lack of treatment options for acute use is concerning Question: Has all of the relevant evidence been taken into account?

Response: It doesn't feel that the use for medication overuse migraines has been properly considered.

Question: Are the recommendations sound and a suitable basis for guidance to the NHS?

No. Rimegepant is an important opportunity to help patients like me with medication overuse migraines.