NICE recommends AMVUTTRA®▼ (vutrisiran) as treatment for a hereditary form of amyloidosis in draft guidance

NICE recommends AMVUTTRA®▼ (vutrisiran) as treatment for a hereditary form of amyloidosis in draft guidance

• Vutrisiran is one of the first rare disease medicines to receive a positive draft recommendation under a streamlined pilot process from the National Institute for Health and Care Excellence (NICE) that aims to expedite patient access to promising new treatments[i]

MAIDENHEAD, UK, 19^th January 2023 – Alnylam UK Limited, the leading RNA interference (RNAi) therapeutics company, today welcomed a draft decision from the National Institute for Health and Care Excellence (NICE) recommending the use of AMVUTTRA^® (vutrisiran) on the NHS in England as an option for treating hereditary transthyretin-related (ATTRv) amyloidosis.[ii] Vutrisiran, a subcutaneous injection administered once every three months, seeks to address the root cause of ATTRv amyloidosis by reducing the production of the abnormal protein (amyloid) that drives this disease. Following final guidance, patients will have the option of vutrisiran, meaning that many may now only need to visit the hospital for treatment every three months, compared to existing therapies that need to be administered every few weeks or more frequently. The guidance is expected to be implemented in Wales in due course.

Professor Julian Gillmore, Consultant at the UCL National Amyloidosis Centre, at the Royal Free Hospital, London, said: “Today’s recommendation of vutrisiran marks another remarkable step forward for patients with hereditary ATTR amyloidosis. This medicine targets the production of amyloid at the source – an approach that we already know can be highly effective at slowing down the symptoms of this condition. Now, we have the ability to do this with an injection that can be given every few months – rather than every other week.”

In cases of ATTRv amyloidosis, one of the proteins that is made by the body is not produced correctly. The protein, which is called transthyretin (TTR), can become abnormal in ATTRv amyloidosis, breaking apart into smaller pieces (amyloid). These deposits can build up in different organs and tissues in the body, such as the nerves, heart, eyes, and gastrointestinal tract, causing damage to them and creating potentially life-threatening health problems. When left untreated, patients can develop polyneuropathy (disease of the peripheral nerves), which can result in a loss of sensation in the lower limbs and hands, autonomic dysfunction (affecting the heart, bladder and intestines, among other organs) and loss of mobility.[iii]

Vince Nicholas, Trustee at the UK ATTR Amyloidosis Patients’ Association (UKATPA), said: “Living with ATTR amyloidosis results in life being incredibly difficult. The symptoms of the disease may strip away the independence of the patient and negatively affects their lives and that of their carers. Patients have to attend numerous appointments in a variety of hospitals depending on the medical input they require. Over the last few years, the amyloidosis community has been very fortunate to have seen the introduction of new medicines funded by the NHS that have greatly improved the future for patients with this debilitating disease. This latest approval has the potential to be a turning point for patients, resulting in fewer treatments and much less time in hospital, leaving more of their time to spend doing what matters most to them.”    

Vutrisiran is an RNAi therapeutic that inhibits the production of the TTR protein by the liver, leading to a reduction in the level of TTR in the blood. By preventing the formation of this protein in patients, it is possible to slow or stop the course of disease, avoiding further damage to patients’ organs and bodily tissues.

Philip Davey, Country Manager of Alnylam Pharmaceuticals, UK and Ireland said: “We are delighted that NICE recognised the potential of vutrisiran and that it will now become one of the first rare disease treatments to become available to patients as a result of this accelerated scheme. Throughout the process, we have collaborated closely with NICE to be able to bring this treatment to eligible patients within a much shorter timeframe. Our hope is that it will offer benefits both for patients suffering from this devasting condition, and for healthcare professionals who provide them with vital care. Our first medicine was recommended for reimbursement on the NHS in England for the treatment of ATTRv amyloidosis in 2019, and this was a moment of great pride for us. Securing this latest guidance for this new advanced medicine would take this pride one step further, demonstrating our commitment to deliver innovative medicines for patients who need them.”

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▼This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcardreporting. Adverse events should also be reported to Alnylam Pharmaceuticals. Email: medinfo@alnylam.com.

Notes to editors

Data from the HELIOS-A study that supported the NICE submission[iv]

The efficacy of vutrisiran was studied in a global, randomised, open-label clinical study (HELIOS-A) in adult patients with hATTR amyloidosis with polyneuropathy. Patients were randomised 3:1 to receive 25 mg of vutrisiran (N=122) subcutaneously once every three months, or 0.3 mg/kg patisiran (N=42) intravenously once every 3 weeks. The treatment period of the study was conducted over 18 months with two analyses at Month 9 and at Month 18.

The primary efficacy endpoint was the change from baseline to Month 18 in modified Neuropathy Impairment Score +7 (mNIS+7). This endpoint is a composite measure of motor, sensory, and autonomic neuropathy including assessments of motor strength, reflexes, quantitative sensory testing, nerve conduction studies, and postural blood pressure, with the score ranging from 0 to 304 points, where an increasing score indicates worsening impairment. Other secondary endpoints included gait speed (10-meter walk test), nutritional status (mBMI), and patient-reported ability to perform activities of daily living and social participation (Rasch-Built Overall Disability Scale [R-ODS]).

Treatment with vutrisiran in the HELIOS-A study demonstrated statistically significant improvements in all endpoints measured from baseline to Month 9 and 18, compared to the external placebo group of the APOLLO study (all p < 0.0001). The time-averaged trough TTR percent reduction through Month 18 was 84.7% for vutrisiran and 80.6% for patisiran. The percent reduction in serum TTR levels in the vutrisiran arm was non-inferior (according to predefined criteria) to the within-study patisiran arm through Month 18 with a median difference of 5.3% (95% CI 1.2%, 9.3%).

During the HELIOS-A 18-month treatment period, the most frequently occurring adverse reactions reported in vutrisiran-treated patients were pain in extremity (15%) and arthralgia (11%).

About ATTRv amyloidosis

Hereditary transthyretin-mediated amyloidosis (ATTRv amyloidosis, historically also referred to as hATTR amyloidosis) is an inherited, progressively debilitating, and often fatal disease caused by mutations in the TTR gene. TTR protein is primarily produced in the liver and is normally a carrier of vitamin A. Mutations in the TTR gene cause abnormal amyloid proteins to accumulate and damage body organs and tissue, such as the peripheral nerves and heart, resulting in intractable peripheral sensory neuropathy, autonomic neuropathy, and/or cardiomyopathy, as well as other disease manifestations.[v]

ATTRv amyloidosis is passed through generations when one parent carries the mutation, giving their children a 50 percent chance of inheriting that mutation (although not all people with the mutation will develop symptoms of the disease).

About AMVUTTRA^® (vutrisiran)

Vutrisiran is an RNAi therapeutic approved in Great Britain for the treatment of hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis) in adult patients with stage 1 or stage 2 polyneuropathy. It is a double stranded small interfering RNA (siRNA) that targets mutant and wild type transthyretin (TTR) messenger RNA (mRNA). Using Alnylam’s Enhanced Stabilization Chemistry (ESC)-GalNAc-conjugate delivery platform, vutrisiran is designed for increased potency and high metabolic stability to allow for subcutaneous injection once every three months (quarterly). Results from the pivotal HELIOS-A Phase 3 study demonstrate that vutrisiran rapidly reduces serum TTR levels, has the potential to reverse neuropathy impairment relative to baseline and improves other key measures of disease burden relative to external placebo in patients with the polyneuropathy of hATTR amyloidosis.

About RNAi

RNAi (RNA interference) is a natural cellular process of gene silencing that represents one of the most promising and rapidly advancing frontiers in biology and drug development today. Its discovery was recognized with the award of the 2006 Nobel Prize for Physiology or Medicine. By harnessing the natural biological process of RNAi occurring in our cells, a class of medicines, known as RNAi therapeutics, is now a reality. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam’s RNAi therapeutic platform, function upstream of today’s medicines by silencing messenger RNA (mRNA) – the genetic precursors – that encode for disease-causing proteins, thus preventing them from being made. This is an approach with the potential to transform the care of patients with genetic and other diseases.

About Alnylam Pharmaceuticals

Alnylam (Nasdaq: ALNY) has led the translation of RNA interference (RNAi) into a whole new class of innovative medicines with the potential to transform the lives of people afflicted with rare and prevalent diseases with unmet need. Based on Nobel Prize-winning science, RNAi therapeutics represent a powerful, clinically validated approach yielding transformative medicines. Since its founding 20 years ago, Alnylam has led the RNAi Revolution and continues to deliver on a bold vision to turn scientific possibility into reality. Alnylam has a deep pipeline of investigational medicines, including multiple product candidates that are in late-stage development. Alnylam is executing on its “Alnylam P5x25” strategy to deliver transformative medicines in both rare and common diseases benefiting patients around the world through sustainable innovation and exceptional financial performance, resulting in a leading biotech profile. Alnylam is headquartered in Cambridge, MA.

References

[i] NICE. Taking a proportionate approach to technology appraisals. Available at: https://bit.ly/3WdVA9M. Last accessed: January 2023.

[ii] NICE. Vutrisiran for treating hereditary transthyretin-related amyloidosis [ID5074]. Last accessed: January 2023.

[iii] Adams, D., Algalarrondo, V., Polydefkis, M. et al. Expert opinion on monitoring symptomatic hereditary transthyretin-mediated amyloidosis and assessment of disease progression. Orphanet J Rare Dis. 2021;16:411. https://doi.org/10.1186/s13023-021-01960-9. Last accessed: January 2023.

[iv] Amvuttra Summary of Product Characteristics. Last accessed: January 2023.

[v] Adams D, Coelho T, Obici L, et al. Rapid progression of familial amyloidotic polyneuropathy. Neurology. 2015;85(8):675-682.  Last accessed: January 2023.