TA868/Scope Consultation Comments
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Summary form

National Institute for Health and Care Excellence

Single Technology Appraisal (STA)

Vutrisiran for treating hereditary transthyretin-related amyloidosis [ID5074]

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
Appropriateness Alnylam
Pharmaceuticals		 Alnylam regards the proposed evaluation of vutrisiran to be appropriate. Thank you for your
comment. No action
required.
National
Amyloidosis
Centre, UCL &
Royal Free
Hospital		 Why is this new treatment, with major benefits to patients’ convenience and
avoidance of steroid pre-meds, not being evaluated as a Highly Specialised
Technology Appraisal, as per inotersen and patisiran? It is a very rare
disease, and this new treatment is essentially identical to patisiran, but
delivered by a much superior 3 monthly sub-cut route in lieu of onerous 3
weekly intravenous infusions that require steroid and other pre-med drugs
each time.		 Thank you for your
comment. NICE
considered that
vutrisiran did not meet
all the criterion listed on
Highly Specialised
Technology checklist.
(UKATPA) and
The UK
Amyloidosis
advisory Group
(UKAAG)		 The evaluation and the evaluation route seem appropriate. Thank you for your
comment. No action
required.

National Institute for Health and Care Excellence

Vutrisiran for treating hereditary transthyretin-related amyloidosis [ID5074] Issue date: September 2022

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Section Consultee/
Commentator		 Comments [sic] Action
Wording Alnylam
Pharmaceuticals		 Alnylam regards the wording of the remit to be appropriate. Thank you for your
comment. No action
required.
National
Amyloidosis
Centre, UCL &
Royal Free
Hospital		 Yes. Thank you for your
comment. No action
required.
(UKATPA) and
The UK
Amyloidosis
advisory Group
(UKAAG)		 Yes. Thank you for your
comment. No action
required.
Timing issues Alnylam
Pharmaceuticals		 Alnylam sees this evaluation as highly urgent for the NHS. Hereditary
transthyretin-mediated (hATTR) amyloidosis is an ultra-rare condition, the
natural course of which is characterised by progressive disability and
mortality due to disease complications. It is currently managed through an
NHS England Highly Specialised Service and a single national treatment
centre, the NHS National Amyloidosis Centre (NAC).
Patisiran is the most used therapeutic in the UK for patients with hATTR
amyloidosis due to its efficacy. Current standard of treatment with patisiran
has associated burdens, including:
A high-touch, time-consuming intravenous (IV) administration process with
frequent dosing (every 3 weeks [Q3W]) with the potential for infusion-
related reactions (IRRs) and IV infusion-related complications at the site
of the peripheral IV catheter, such as extravasation or phlebitis.		 Thank you for your
comment. No action
required.

National Institute for Health and Care Excellence

Vutrisiran for treating hereditary transthyretin-related amyloidosis [ID5074] Issue date: September 2022

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Section Consultee/
Commentator		 Comments [sic] Action
A premedication regimen with associated adverse effects, required every
treatment session to minimise the risk of IRRs.
**************************************************************************************
**********************************************************************************
*************************************************************Travel by patients
across England to the NAC in London for initial treatments, potentially
requiring significant travel for patients with hATTR amyloidosis. The
summary of product characteristics (SmPC) for patisiran states patisiran
can be considered for delivery via homecare after at least 3 well-
tolerated infusions in a clinic.1Currently, all patients in the UK are
moved to homecare for patisiran administration following treatment
initiation at the NAC.
Alnylam estimates a single treatment session with patisiran can take 3.5
hours not including travel, consisting of:
Premedication regimen ≥ 60 mins before patisiran infusion, consisting of an
IV corticosteroid (dexamethasone 10 mg or equivalent), H1 blocker
(diphenhydramine 50 mg or equivalent), H2 blocker, and oral
paracetamol.1
In the event of a shortage of any component of premedication, treatment
would be severely compromised for patients with hATTR amyloidosis.
IV infusion which takes approximately 80 mins.
Patient monitoring post-infusion which takes approximately 60 mins.
In addition, Alnylam estimates that treatment fatigue or drowsiness from
premedication can last up to 2 days.
Patients are also typically fragile and elderly, amplifying these negative
impacts of treatment and potentially decreasing treatment adherence.
Furthermore, as noted, patients on patisiran are reliant on a robust
homecare delivery service requiring the availability of healthcare
professionals (HCP) trained to provide IV infusions. Alnylam notes that
homecare delivery servicesin the UKare experiencing chroniclong-term

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Section Consultee/
Commentator		 Comments [sic] Action
staff shortages, potentially jeopardising the administration of patisiran to
patients in accordance with their ongoing Q3W treatment schedule.
Similarly, the NAC has limited infusion capacity for patients with hATTR
amyloidosis and is also reliant on robust clinic staffing. Of note, the
European Medicines Agency (EMA) Committee for Orphan Drug Medicinal
Products (COMP) concluded that for treatment with patisiran, 2–10 hours of
active HCP time is lost per patient with hATTR amyloidosis per year.2
Alnylam notes chronic nurse staffing challenges in the UK NHS particularly
as a result of the COVID pandemic3; thus, should there be a failure of
homecare delivery in the UK, it is unlikely that the NAC could accommodate
patisiran infusions for all patients affected.
Therefore, there is an urgent need for a therapy that has comparable
effectiveness to patisiran but lacks the associated important limitations.
Eliminating the burdens of patisiran would benefit patients, their carers,
HCPs, and NHS England, and importantly, would minimise the risks of
treatment interruption in this progressive and fatal disease.
Vutrisiran is an effective therapy for patients with hATTR amyloidosis that
will be administered:
Every 3 months i.e., 4 times per year as opposed to 17–18 times per year
for patisiran.
By subcutaneous (SC) injection, which is a less resource- and labour-
intensive mode of administration compared to IV administration for
patisiran.
The introduction of vutrisiran would reduce treatment burden on patients
and their carers in addition to decreasing the resource demands on the NHS
system. The full extent of benefits vutrisiran would provide are discussed
below in more detail in a response to a ‘NICE question for consultation’,
specificallyrespondingtothe questionposingwhether vutrisiran would

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Section Consultee/
Commentator		 Comments [sic] Action
produce a substantial impact on health-related benefits, or a ‘step-change’
in management. Some of these substantial impacts include:
Eliminating the risk of IRRs and the need for administration of a
premedication regimen associated with IV administration of patisiran,
due to the SC route of administration for vutrisiran.
Minimising the risk to patients with hATTR amyloidosis of an inability to
deliver their treatment, by greatly reducing the treatment burden placed
on homecare providers and the NAC in terms of both the frequency of
administrations (every quarter vs. every 3 weeks with patisiran) and the
time required per administration (less than 5 minutes vs. more than an
hour).
Contributing to alleviating the pressures faced by the UK healthcare system
since vutrisiran can be administered in a variety of outpatient settings, in
contrast to the need for a lengthy hospital visit to the NAC or healthcare
home visits for IV infusion of patisiran.
In the current COVID environment, with an increasing rate of COVID-related
hospitalisation in July 2022,4the use of vutrisiran may minimise the risk
of COVID transmission in the highly vulnerable older age target
population by reducing patients’ frequency and intensity of healthcare
contacts. Furthermore, these benefits would be realized in respect to all
iatrogenic infections.
The advantages that vutrisiran provides over patisiran to patients with
hATTR amyloidosis, their carers, and clinicians would therefore address an
urgent unmet need and would be experienced immediately upon patient
switch from patisiran to vutrisiran treatment.
Recognising the urgent need, Alnylam has been proactive in engaging with
NHS England and NICE since 2021 to understand how to best collaborate
to ensure the benefits of vutrisiran are realised in England as soon as
possible.

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Vutrisiran for treating hereditary transthyretin-related amyloidosis [ID5074] Issue date: September 2022

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Section Consultee/
Commentator		 Comments [sic] Action
Alnylam notes, with great interest, discussion of a ‘proportionate approach’
by NICE, particularly related to potential pilots for lighter-touch evaluation
approaches, where appropriate, to better utilise NICE resources and enable
patients to benefit from new therapies more rapidly.5,6Alnylam believes it
would be rational for such an approach to be applied to vutrisiran,
considering the health economics are well understood after the highly
specialised technology (HST) appraisal of patisiran for the same population
of patients with hATTR amyloidosis in 2018/19,7and the comparable clinical
efficacy between vutrisiran and patisiran with the aforementioned added
benefits vutrisiran provides.
Alnylam is very eager to learn more and to participate in a proportionate
approach pilot. We would encourage NICE engagement with Alnylam to
discuss any plans for pilots, as it would allow patients with hATTR
amyloidosis to benefit from vutrisiran sooner than currently proposed
appraisal timelines.
The Department for Health and Social Care published the UK Rare Disease
Framework in 2021. In this framework, four main priorities for patients with
rare diseases in the UK are set out, including better coordination of care and
improved access to treatment.8Making vutrisiran available to patients with
hATTR amyloidosis aligns strongly with these priorities and further supports
the urgency of this appraisal.
National
Amyloidosis
Centre, UCL &
Royal Free
Hospital		 The new technology is essentially a reformulated version of patisiran with
very substantial advantages to patients – simple 3 monthly sub-cut
injections vs onerous 3 weekly i.v. infusions requiring pre-medication with
steroids and antihistamines etc. It would be a great shame if this new
development cannot be implemented urgently into NHS rare disease
practice.		 Thank you for your
comment. No action
required.

National Institute for Health and Care Excellence

Vutrisiran for treating hereditary transthyretin-related amyloidosis [ID5074] Issue date: September 2022

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Section Consultee/
Commentator		 Comments [sic] Action
(UKATPA) and
The UK
Amyloidosis
advisory Group
(UKAAG)		 This drug may be suitable for patients that are intolerant or not suitable to
have patisiran or inotersen. Vutisiran could save their lives.
Vutisiran does not require pre-medication (patisiran does), which makes it
easier to adminster and reduces side effects from the premedication. It may
save money to the NHS since it is administered once every 13 weeks.		 Thank you for your
comment. No action
required.
Any additional
comments on the
draft remit		 Alnylam
Pharmaceuticals		 NA Thank you for your
comment. No action
required.
National
Amyloidosis
Centre, UCL &
Royal Free
Hospital		 NA Thank you for your
comment. No action
required.
(UKATPA) and
The UK
Amyloidosis
advisory Group
(UKAAG)		 NA Thank you for your
comment. No action
required.
Background
information		 Alnylam
Pharmaceuticals		 Commonly used disease progression schemes for patients with hATTR
amyloidosis include the familial amyloid polyneuropathy (FAP) staging
system and the polyneuropathy disability (PND) scoring system. In the
Background section of the draft scope, FAP is used to define levels of
neuropathy; however, in the Questions for consultation section, stage 4
polyneuropathyismentioned,indicatingPNDscore (excluding stage 0,FAP		 Thank you for your
comment. No action
required.

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Section Consultee/
Commentator		 Comments [sic] Action
staging includes 3 stages [stages 1, 2, and 3], while PND score is more
detailed and includes 5 stages [stages 1, 2, 3a, 3b, and 4]).
The European SmPC states that vutrisiran is indicated for the treatment of
hATTR amyloidosis in adult patients with stage 1 or stage 2 polyneuropathy,
defined by FAP stage.
National
Amyloidosis
Centre, UCL &
Royal Free
Hospital		 Should clarify the similarity of new drug with patisiran but emphasising
superiority of delivery mechanism, allowing 3 monthly sub-cut administration
without hefty steroid and other pre-medication. Need to be clear the new
treatment is not an add-on but would be a substitution for current first
generation gene silencers, i.e. a second generation treatment.		 Thank you for your
comment. The
background section of
the scope aims to
provide a brief
summary of the disease
and how it is managed,
it is not designed to be
exhaustive in its detail.
No changes were made
to the scope.
(UKATPA) and
The UK
Amyloidosis
advisory Group
(UKAAG)		 The background information is true, but it is a simplification.
It gives the impression that the main problem for the patient is losing the
ability to walk. This is a progressive and devastating disease that can cause
constant and severe pain, even at night disturbing sleep; The severe
diarrhea often causes social isolation and malnutrition. Loss of hand
function causes loss of independence of the patients and severe disability.
Urinary symptoms, loss of sexual function, loss of sight and mental
deteriroration		 Thank you for your
comment. The
background section of
the scope aims to
provide a brief
summary of the disease
and how it is managed,
it is not designed to be
exhaustive in its detail.
More details on the
disease and its
complications will be
discussed duringthe

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Section Consultee/
Commentator		 Comments [sic] Action
appraisal. No changes
were made to the
scope.
Population Alnylam
Pharmaceuticals		 Alnylam regards the population definition to be appropriate; however, it
should be noted that the European SmPC states that vutrisiran is indicated
for the treatment of hATTR amyloidosis in adult patients with stage 1 or
stage 2 polyneuropathy.		 Thank you for your
comment. No action
required.
National
Amyloidosis
Centre, UCL &
Royal Free
Hospital		 It has become clear that a small proportion of black individuals carrying the
TTR V122I gene variant have amyloid polyneuropathy that would be an
indication for treatment. Currently, this population are presenting late and a
much more patient-friendly administration route may well be advantageous
in gaining engagement from the Afro-Caribbean population.		 Thank you for your
comment. No action
required.
(UKATPA) and
The UK
Amyloidosis
advisory Group
(UKAAG)		 Yes Thank you for your
comment. No action
required.
Subgroups Alnylam
Pharmaceuticals		 Alnylam regards the population definition without subgroups as appropriate. Thank you for your
comment. No action
required.
National
Amyloidosis
Centre, UCL &
Royal Free
Hospital		 Note above. Thank you for your
comment. No action
required.

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Section Consultee/
Commentator		 Comments [sic] Action
(UKATPA) and
The UK
Amyloidosis
advisory Group
(UKAAG)		 NA Thank you for your
comment. No action
required.
Comparators Alnylam
Pharmaceuticals		 Are inotersen and patisiran relevant comparators?
Which treatments are considered to be established clinical practice in the
NHS for hATTR amyloidosis?
In accordance with section 1.2 of the NICE procedure note for the draft
scope, Alnylam considers that, for the evaluation to be most efficient, the
only relevant comparator for vutrisiran is patisiran.
While both patisiran and inotersen are recommended by NICE, patisiran is
the current standard of care for patients with hATTR amyloidosis in England
and it alone constitutes established clinical practice.
Based on Alnylam’s understanding of UK clinical practice at the NAC and
reflected in product market shares, patisiran is currently utilized in all
treatment-eligible patients with hATTR amyloidosis as the first-choice
therapy. Inotersen use is reserved for exceptional circumstances only for
patients who are unable to receive patisiran for non-clinical reasons, for
example due to homecare availability challenges. Thus, inotersen does not
occupy the same positioning in the treatment pathway as patisiran in
England.
Additionally, NAC clinicians

 and
*****************************************************		 Thank you for your
comment. At the
scoping stage of the
appraisal, identification
of comparators should
be inclusive. The
potential comparators
listed in the scope
represent treatments
used to treat hereditary
transthyretin-related
amyloidosis in NHS
clinical practice. Any
exclusion from the
decision problem in the
company submission
should be fully justified
and will be considered
during the course of the
appraisal.

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Section Consultee/
Commentator		 Comments [sic] Action
, have informed Alnylam that they foresee vutrisiran replacing patisiran as
the standard of care for patients with hATTR amyloidosis in the UK.
Based on prior communication in January 2022 with
,




*************************************************************
***********************************
**************************

*********** This highlights the increasing irrelevance
of inotersen since it is plausible that no patients in England, or very few
future patients in England, will be receiving inotersen in the near future.
Alnylam also notes in HST9 for inotersen, the committee stated that:11
“Clinical trial evidence shows that inotersen slows progression of the
disease considerably, although its long-term benefits are uncertain.”
In contrast, in HST10 for patisiran, the committee stated that:7
“Clinical trial evidence shows that patisiran reduces disability and
improves quality of life, by enabling patients to return to work, carry
out daily activities, participate in a more active family and social life,
and maintain their independence and dignity. There is also evidence
suggesting that patisiran may provide long-term benefits by stopping
the progression of amyloidosis and potentially reversing it.”
Alnylam also notes contraindications exclusive to inotersen include: platelet
count < 100 x 109/L prior to treatment; urine protein to creatinine ratio
(UPCR) ≥ 113 mg/mmol (1 g/g) prior to treatment; estimated glomerular

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Section Consultee/
Commentator		 Comments [sic] Action
filtration rate (eGFR) < 45 ml/min/1.73 m2[moderate to severe loss of kidney
function]; and severe hepatic impairment.12
It is important to note that the single listed contraindication for vutrisiran is
identical to that of patisiran, namely hypersensitivity to the active ingredient
or excipients.1,10Of note, the EMA COMP noted:2
“In contrast, the SmPC for vutrisiran does not have these
contraindications [of inotersen], thus broadening the patient population
addressable by vutrisiran compared to inotersen. Vutrisiran SmPC
also does not require monitoring since there were no effects seen on
platelet counts or any evidence of renal toxicity in the HELIOS-A
study, which included 4 patients with eGFR 30-45 mL/min/1.73m2at
baseline [i.e., patients who would be ineligible for treatment with
inotersen per its labelled contraindications].”
Are other experimental treatments such as doxycycline plus
tauroursodeoxycholic acid comparators?
Experimental treatments, including doxycycline plus tauroursodeoxycholic
acid, are not relevant comparators for inclusion in the appraisal because
none of these treatments are commonly used or part of the pathway of care
in the UK for patients with hATTR amyloidosis with polyneuropathy. In the
appraisal of inotersen, experts from the NAC confirmed that doxycycline
plus tauroursodeoxycholic acid is not used in the UK, and thus these were
explicitly excluded from the scope.13Given their irrelevance even back in
2018, Alnylam sees these experimental treatments even more irrelevant
now in 2022 when other authorized treatments are available.
Are there any other treatments that should be included as comparators?
Alnylam does not regard any other treatment options besides patisiran as
relevant comparators. The evidence base for vutrisiran also supports the		 .

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Section Consultee/
Commentator		 Comments [sic] Action
relevance of the comparison versus patisiran, since the HELIOS-A trial
included both of these small interfering RNA therapies.
National
Amyloidosis
Centre, UCL &
Royal Free
Hospital		 Yes, but note that diflunisal is not funded at present and not easy to access. Thank you for your
comment. No action
required.
(UKATPA) and
The UK
Amyloidosis
advisory Group
(UKAAG)		 Patisiran and inotersen seem to be the correct comparators. All other drugs
mentioned are not comparators, in our view.		 Thank you for your
comment. No action
required.
Outcomes Alnylam
Pharmaceuticals		 Alnylam regards the outcome measures proposed as appropriate.
Is serum transthyretin a relevant outcome?
Serum transthyretin (TTR) is a relevant outcome measure for trials in
hATTR amyloidosis. Transthyretin is a tetrameric protein composed of four
monomers.14In the case of transthyretin-mediated amyloidosis, the
tetrameric protein destabilises into unstable monomers and TTR fragments
that can misfold and form amyloid fibril deposits in multiple organs, including
the peripheral nervous system, heart, and GI tract, leading to cellular injury
and organ dysfunction with corresponding clinical manifestations.14-17The
patisiran SmPC and European vutrisiran SmPC highlight that the
mechanism of action for both patisiran and vutrisiran is reducing serum and
tissue TTR levels through mRNA interference pathways in the liver.1,10
Additionally, in HST10 for patisiran, it was noted by NICE that clinical
experts agree that the stopping or reversing amyloid deposition and
decreasing subsequent neuropathy is dependent on the reduction of serum		 Thank you for your
comment. No action
required.

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Section Consultee/
Commentator		 Comments [sic] Action
TTR.7Evidence from the HELIOS-A trial showed a rapid and sustained
reduction in serum TTR levels in patients treated with vutrisiran, noninferior
to within-study patisiran as demonstrated by a prespecified secondary
endpoint analysis at Month 18.18Therefore, serum TTR is a relevant
outcome for trials in hATTR amyloidosis. However, due to a potential lack of
assay reagent availability, assay variability, and intra-patient variability in
peak to trough serum TTR levels at any given point in time, serum TTR
levels may have less relevance as an outcome measure in routine clinical
practice.
Which elements of autonomic function are affected by the condition and
might be improved by vutrisiran?
hATTR amyloidosis is a multisystem disease with heterogeneous clinical
presentation that includes sensory, motor, and autonomic (e.g., diarrhea,
sexual dysfunction, orthostatic intolerance) polyneuropathy and
cardiomyopathy, with the potential involvement of other organ systems as
well.14,17,19,20The primary endpoint of the HELIOS-A study was based on
mNIS+7,18which assesses the progression of the motor and the sensory
aspects of polyneuropathy, as well as some autonomic manifestations, such
as postural hypotension, and correlates with both FAP and PND scores.
Autonomic assessment from mNIS+7 at Month 9 and 18 of the HELIOS-A
trial demonstrated improvement in autonomic nerve function for patients on
vutrisiran compared to placebo.21,22
The Norfolk Quality of Life – Diabetic Neuropathy (QoL-DN) questionnaire
was a secondary endpoint in the HELIOS-A trial.18One of the 5 domains of
the Norfolk QoL-DN questionnaire assesses symptoms of autonomic nerve
dysfunction and their impact on activities of daily living. Significant
improvements in this domain of the Norfolk QoL-DN questionnaire were
observed in vutrisiran-treated patients when compared to placebo in the
HELIOS-A trial.21

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Commentator		 Comments [sic] Action
Modified body mass index (mBMI) was also a secondary endpoint in the
HELIOS-A trial.18mBMI (BMI multiplied by serum albumin concentration
[g/L]) is understood to be an important indicator of autonomic
gastrointestinal nerve function.23Further enhancements in autonomic
function were demonstrated by significantly improved mBMI measures in
vutrisiran-treated patients when compared to placebo in the HELIOS-A
trial.21
Therefore, all relevant data indicate that vutrisiran improves autonomic
function in patients affected by hATTR amyloidosis. Data from the APOLLO
trial for patisiran also demonstrated significant improvement in mBMI and
improvements in the autonomic domain of the Norfolk QoL-DN
questionnaire in patients with hATTR amyloidosis treated with patisiran
compared to placebo, demonstrating similarities in autonomic improvement
for vutrisiran and patisiran.24,25
Would vutrisiran have an effect on cardiomyopathy outcomes?
The effects of vutrisiran on patients with transthyretin amyloidosis (ATTR)
with cardiomyopathy are currently being explored in the ongoing phase 3,
randomised, double-blind, placebo-controlled, multicenter study, HELIOS-
B.26Alnylam does not consider that cardiomyopathy measures are relevant
to include in the present scope for patients with hATTR amyloidosis with
polyneuropathy considering Alnylam is proposing a cost comparison
submission against patisiran which is approved to treat patients with hATTR
amyloidosis with polyneuropathy. Please see below response to ‘NICE
question for consultation’, specifically regarding the appropriateness of
using cost-comparison methodology for vutrisiran.
National
Amyloidosis
Centre, UCL &		 Need to consider the benefit to patients related to 3 monthly sc vs current
much more onerous 3 weekly infusions.		 Thank you for your
comment. No action
required.

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Section Consultee/
Commentator		 Comments [sic] Action
Royal Free
Hospital
(UKATPA) and
The UK
Amyloidosis
advisory Group
(UKAAG)		 Yes.
The modified mNIS + 7 (mNIS + 7) scale was specifically designed to
assess polyneuropathy impairment in patients with hATTR amyloidosis.
The autonomic symptoms of the disease are very intrusive and often
understimated.		 Thank you for your
comment. No action
required.
Equality and
diversity		 Alnylam
Pharmaceuticals		 Alnylam does not consider that the draft remit and scope need to be
modified to meet equality goals.		 Thank you for your
comment. No action
required.
National
Amyloidosis
Centre, UCL &
Royal Free
Hospital		 NA Thank you for your
comment. No action
required.
(UKATPA) and
The UK
Amyloidosis
advisory Group
(UKAAG)		 The population is defined as: “People with hereditary transthyretin-related
amyloidosis”
There are over 100 mutations of the TTR gene, resulting in different
presentations of the disease.
Caucasian patients tend to have some mutations that result in more
neuropathy and less cardiomyopathy (eg V30M), while patients from the
black community tend to develop more cardiomyopathy and fewer
neurological symptoms (eg V122I).
Will patients from the black community be disadvantaged?		 Thank you for your
comment. The
appraisal committee will
consider the impact of
its recommendations on
protected
characteristics as
stated in equality
legislation during the
appraisal. No action
required.

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Section Consultee/
Commentator		 Comments [sic] Action
Patients with more advanced disability or those who live in remote areas
have significant difficulties travelling for treatment. A treatment that
minimises inconvenience has a higher value for these patients. It would be
ideal if the treatment could be home delivered to the patients, in the same
way
Other
considerations		 Alnylam
Pharmaceuticals		 Alnylam does not have any additional issues to suggest. Thank you for your
comment. No action
required
National
Amyloidosis
Centre, UCL &
Royal Free
Hospital		 NA Thank you for your
comment. No action
required.
(UKATPA) and
The UK
Amyloidosis
advisory Group
(UKAAG)		 The two drugs that are currently available have many positive benefits which
as patients have been appreciated. Vutisiran, that is administered by
injection every 13 weeks is a step change that is proving to be positive
compared with Patisiran and Inoterson. Patisiran is administered every 3
weeks with a nurse visiting the patient’s home for three hours at a time. This
includes giving the patient a variety of drugs which depending on the
patient, does/can have adverse effects.
Moving to an injection every 13 weeks will reduce the cost and demands of
the nursing staff providing the treatment. Inoterson is a weekly injection that
is self- administered which some patients have issues with doing. Added to
this a nurse visits the patient every two weeks to take bloods for evaluation
thatagain willbehigh incostandnursetime.		 Thank you for your
comment. No action
required.
Questions for
consultation		 Alnylam
Pharmaceuticals		 NA Thank you for your
comment. No action
required.

National Institute for Health and Care Excellence

Vutrisiran for treating hereditary transthyretin-related amyloidosis [ID5074] Issue date: September 2022

Page 18

Summary form

Section Consultee/
Commentator		 Comments [sic] Action
(UKATPA) and
The UK
Amyloidosis
advisory Group
(UKAAG)		 NA Thank you for your
comment. No action
required.
Additional
comments on the
draft scope		 Alnylam
Pharmaceuticals		 Alnylam would welcome a scoping workshop with clinicians present to
further discuss NICE’s view on the appropriateness of our current plan for a
vutrisiran cost comparison submission against patisiran. Alnylam is fully
prepared to make a cost comparison submission in late Q3 or early Q4
2022, and as previously raised with the scoping team, is keen to discuss the
possibility to expedite the appraisal from currently communicated timelines
for the benefit of patients, carers, HCPs, and NHS England.
As noted in this document, Alnylam is greatly interested in the ‘proportionate
approach' being considered by NICE, particularly for potential pilots for
lighter-touch evaluations where appropriate.5,6 Again, we believe it would
be rational to apply such an approach to vutrisiran considering that the
health economics are well understood and considering an HST appraisal of
patisiran was performed for the same population of patients with hATTR
amyloidosis in 2018/19.7 This is also supported by the comparable clinical
efficacy between vutrisiran and patisiran with the added benefits vutrisiran
offers.
Alnylam is very eager to learn more and to participate in a proportionate
approach pilot and would encourage NICE to engage with Alnylam to
discuss any plans for pilots, if it would allow patients to benefit from
vutrisiran sooner than currently proposed appraisal timelines.		 Thank you for your
comment. No action
required.
National
Amyloidosis		 It is very difficult to understand why NICE is not conducting this new therapy
as a HST appraisal.		 Thank you for your
comment. NICE

National Institute for Health and Care Excellence

Vutrisiran for treating hereditary transthyretin-related amyloidosis [ID5074] Issue date: September 2022

Page 19

Summary form

Section Consultee/
Commentator		 Comments [sic] Action
Centre, UCL &
Royal Free
Hospital		 considered that
vutrisiran did not meet
all the criterion listed on
Highly Specialised
Technology checklist.
(UKATPA) and
The UK
Amyloidosis
advisory Group
(UKAAG)		 The aproval of patisiran and inotersen represented a huge step ahead for
ATTR amyloidosis patients.
The approval of vutisiran would represent another very significant step in the
treatment of this devastating disease.		 Thank you for your
comment. No action
required.

National Institute for Health and Care Excellence

Vutrisiran for treating hereditary transthyretin-related amyloidosis [ID5074] Issue date: September 2022