First therapy to target the underlying cause of a life-threatening form of porphyria to be made available on the NHS in England

First therapy to target the underlying cause of a life-threatening form of porphyria to be made available on the NHS in England

• GIVLAARI®▼ (givosiran) uses ‘gene silencing’ RNA interference technology to targetthe production of pathogenic compounds in people with acute hepatic porphyria (AHP).1
• The decision was based on data from a Phase III study in which treatment led to a 74% reduction in the annualised composite rate of porphyria attacks relative to placebo.2

MAIDENHEAD, UK, 21 OCTOBER 2021 – Alnylam UK Limited, the leading RNAinterference (RNAi) therapeutics company, today welcomed a decision from the National Institute for Health and Care Excellence (NICE) recommending the use of GIVLAARI® (givosiran) on the NHS in England as an option for the treatment of acute hepatic porphyria (AHP) in people 12 years and older who have clinically confirmed severe recurrent attacks (4 attacks or more within 12 months). Today, NICE has published a Final Evaluation Determination (FED) following a Highly Specialised Technology (HST) appraisal. AHP refers to a family of ultra-rare, genetic diseases characterised by extremely painful, potentially life-threatening attacks. Some patients with AHP may experience recurrent attacks that can require periods of hospitalisation, as well as ongoing chronic symptoms.3 Givosiran is the first and only treatment that addresses the underlying cause of this disease.4

Professor David Rees, Professor of Haematology at King’s College London and Director of the King's College Hospital National Acute Porphyria Service said: “It is hard to overstate the lifelimiting impact of this condition on patients and their families. Some patients experience regular, intense pain, have to spend long periods of time in hospital and be unable to continue working or have a normal social life. By using this pioneering ‘gene silencing’ approach, we can now target the production of toxic compounds that have the potential to wreak havoc in the body – tackling the cause of a patient’s attacks at the source. We now have a better chance to help many of those affected live a more normal life.”

AHP is caused by a genetic defect that can be passed down through generations. As a result, it is not uncommon for multiple siblings or close relatives within a family to be affected.1 People with AHP lack certain enzymes needed to produce haem, a basic structure of the blood protein haemoglobin, As a result, substances used to make haem (porphyrin precursors) can build up the body to toxic levels. Givosiran works by using RNAi to reduce the build-up of the porphyrin precursors, thereby potentially reducing attack frequency and chronic symptoms.2 In the ENVISION Phase III clinical trial, published in the New England Journal of Medicine, givosiran demonstrated a 74% reduction in the annualised composite rate of porphyria attacks in patients with Acute Intermittent Porphyria (a common subtype of AHP), relative to placebo.2

John Chamberlayne, Chairman at The British Porphyria Association said: “For decades, people with this life-threatening condition have had limited options to control the relentless and debilitating pain, nausea, and fatigue that dominate virtually all aspects of their lives. The decision today from NICE is therefore a very welcome and important one. It will mark real change for patients and families in future, allowing more people to live without the constant fear of when the next agonising attack may strike.”

AHP is a rare disease and around 17 patients across the UK are diagnosed each year. For many patients, diagnosis can be a complex journey with some patients reporting symptoms for 14 years before diagnosis. 

Brendan Martin, SVP, General Manager, UK & Ireland at Alnylam Pharmaceuticals said: “At Alnylam, our goal is to translate the science of RNAi into new medicines that can treat rare and serious diseases, but our ultimate priority is to ensure that eligible patients living with these conditions are able to access them. Today’s decision makes givosiran the third RNAi medicine to be made available via the NHS in as many years, and we are grateful to the physicians and patients who have contributed to the NICE process, enabling the AHP community to have access to this important treatment option.”

##

1 NICE. Givosiran for treating acute hepatic porphyria [ID1549]. Available at: https://www.nice.org.uk/guidance/indevelopment/gid-hst10035. Last accessed: October 2021 
2 Balwani, M., Sardh, E., Ventura, P. et al. Phase 3 Trial of RNAi Therapeutic Givosiran for Acute Intermittent Porphyria. N Eng J Med 2020; 382:2289-2301. Available at: https://doi.org/10.1056/NEJMoa1913147.
3 Gill, L., Burrell, S., Chamberlayne, J. et al. Patient and caregiver experiences of living with acute hepatic porphyria in the UK: a mixed-methods study. Orphanet J Rare Dis 2021;16(187). Available at: https://doi.org/10.1186/s13023-021-01816-2. 
4 Givosiran NICE Committee papers. Key fact available at committee-papers (nice.org.uk) Last accessed October 2021.
5 Kuter, D., Keel, S., Parker, C., et al. Eighteen-Month Interim Analysis of Efficacy and Safety of Givosiran, an RNAi Therapeutic for Acute Hepatic Porphyria, in the ENVISION Open-Label Extension. Presented at American Society of Hematology (ASH) Congress December 2020. Available at: https://bit.ly/3kWYob3. Last accessed: October 2021.
6 Givlaari 189 mg/mL solution for injection. Summary of Product Characteristics. Updated October 2021. Available at: https://bit.ly/3lMZnuS. Last accessed: October 2021.
7 Bonkovsky, H., Maddukuri, V., Yazici, C. et al. Acute Porphyrias in the USA: Features of 108 Subjects from Porphyria Consortium. Am J Med. 2014; 127(12):1233–1241. Available at: https://bit.ly/3oi8u8x.

AS1-UK-00023
Date of preparation: October 2021