Jan 13, 2025
  • Scottish Medicines Consortium (SMC) has recommended Fabhalta®▼ (iptacopan) as monotherapy for adults with paroxysmal nocturnal haemoglobinuria (PNH) who have haemolytic anaemia and used under the advice of the National PNH Service.
  • Iptacopan is the first oral PNH monotherapy; current standard of care requires treatment with intravenous infusions
  • Approximately 210 people live with PNH in Scotland. The symptoms of PNH may be burdensome and result in people with the disease having lower quality of life compared with the general population as they may be anaemic, fatigued and dependent on blood transfusions.1-4,17

Edinburgh, 13 January 2025 - Today, Novartis announced that the Scottish Medicines Consortium (SMC) has published advice recommending Fabhalta®▼ (iptacopan) for use on the NHS in Scotland as an option for treating paroxysmal nocturnal haemoglobinuria (PNH) in adults with haemolytic anaemia. Iptacopan can only be used under the advice of the National PNH Service.

PNH is a rare blood disease where red or white blood cells are vulnerable to being attacked by a particular part of the body’s immune system called “the complement system”5-8.The process by which red blood cells are destroyed is called haemolysis and is responsible for many PNH symptoms, including fatigue.8,9 Up to 80% of patients with PNH experience fatigue caused by anaemia, having a direct impact on quality of life and it means they can also require blood transfusions.3,4,8-10

Responding to the announcement, Lesley Loeliger, Founder and Chair of PNH Scotland said: “The announcement by the SMC that iptacopan is to be made available in Scotland is good news for patients and families living with PNH. The option of an oral monotherapy for patients with PNH and haemolytic anaemia is exciting. We would like to thank the SMC for allowing the patient voice to be heard during the evaluation of medicines for rare diseases.” 

Dr Morag Griffin, Consultant Haematologist at Leeds Teaching Hospitals NHS Trust said, "We at the National PNH service are pleased with the approval of iptacopan as the first oral monotherapy for people living with PNH in Scotland. Trial data has shown iptacopan can be effective in improving haemoglobin levels and controlling the destruction of red blood cells that causes many of the symptoms of PNH. I look forward to working with the team at University Hospital Monklands to get this treatment to eligible patients"

The decision was based on the APPLY-PNH and APPOINT-PNH Phase III clinical trials. The APPLY-PNH study compared iptacopan with C5 inhibitor therapies in adult patients with PNH presenting with persistent anaemia despite a stable regimen of C5 inhibitor therapies. The APPOINT-PNH study was a single arm study of iptacopan in adult PNH patients who are naïve to C5 inhibitor therapies.11

The most commonly reported adverse reactions for iptacopan were upper respiratory tract infection (18.9%), headache (18.3%) and diarrhoea (11.0%). The most commonly reported serious adverse reaction was urinary tract infection (1.2%). There were no deaths, and no patients stopped treatment or interrupted treatment due to adverse events (side effects) in either trial 11

“We were pleased to secure access to the first oral monotherapy for PNH patients in England and Wales in September, and it’s great that iptacopan is now an option for patients in Scotland too,” said Johan Kahlström, Country President Novartis UK and Ireland. “At Novartis, we are continuing to demonstrate how committed we are to delivering potentially practice changing treatments in rare diseases.” 

About Paroxysmal Nocturnal Haemoglobinuria

PNH is a rare, chronic and serious complement-mediated blood disorder.6,9,11,12 People with PNH have an acquired mutation in some of their haematopoietic stem cells that causes them to produce red blood cells susceptible to premature destruction by the complement system.Error! Reference source not found.6,9,12,13 This leads to intravascular haemolysis (destruction of red blood cells within blood vessels) which causes anaemia (low levels of circulating red blood cells), thrombosis (formation of blood clots) and other debilitating symptoms.9,12
  
It is estimated that approximately 10-20 people per million worldwide live with PNH.12 Although PNH can develop at any age, it is often diagnosed in people between 30-40 years old.5,6

About Fabhalta®▼ (iptacopan)                                                          

Iptacopan is an oral, Factor B inhibitor of the alternative complement pathway.14,15 Iptacopan 200 mg capsules are administered as an oral treatment twice daily.

▼ This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals and patients are asked to report any suspected adverse reactions. Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard. Adverse events should also be reported to Novartis online through the pharmacovigilance intake (PVI) tool at www.novartis.com/report or alternatively email [email protected] or call 01276 698370.

About APPLY-PNH 

APPLY-PNH (NCT04558918) was a Phase III, randomised, multinational, multicentre, active-comparator controlled, open-label trial to evaluate the efficacy and safety of twice-daily, oral iptacopan monotherapy (200 mg) for the treatment of PNH by assessing if switching to iptacopan was superior to continuing on C5 inhibitor therapies (eculizumab or ravulizumab) in adult patients presenting with residual anaemia (haemoglobin <10 g/dL) despite a stable regimen of C5 inhibitor treatment in the last six months prior to randomisation. The trial enrolled 97 patients who were randomised in an 8:5 ratio to either twice-daily, oral iptacopan monotherapy, or intravenous infusion C5 inhibitor therapies (continuing with the same regimen as they were on prior to randomisation).11

About APPOINT-PNH

APPOINT-PNH (NCT04820530) was a Phase III, multinational, multicentre, open-label, uncontrolled single-arm study to evaluate the efficacy and safety of twice-daily, oral iptacopan monotherapy (200 mg) in adult PNH patients who are naïve to complement inhibitor therapy, including C5 inhibitor therapies (eculizumab or ravulizumab). The trial enrolled 40 patients who received twice-daily, oral iptacopan monotherapy.11

About Novartis

Novartis is an innovative medicines company. Every day, we work to reimagine medicine to improve and extend people’s lives so that patients, healthcare professionals and societies are empowered in the face of serious disease. 

In the UK, we champion health and lives through pioneering NHS partnerships, innovative collaborations and a clear focus on the greatest healthcare challenges we all face. We are where science meets hope.

To reimagine medicine with us, visit our website at https://www.novartis.com/uk-en/ and connect on LinkedInFacebook, and Instagram.

UK | January 2025 | MLR ID: FA-11341511

References

  1. Richards S, Painter D, Dickinson A et al. The incidence and prevalence of patients with paroxysmal nocturnal haemoglobinuria and aplastic anaemia PNH syndrome: A retrospective analysis of the UK's population-based haematological malignancy research network 2004-2018. Eur J Haematol. 2021 Aug. 107(2):211-218
  2. Risitano AM, Peffault de Latour R. How we (’ll) treat paroxysmal nocturnal haemoglobinuria: diving into the future. British Journal of Haematology. 2022 Jan;196(2):288-303.
  3. Bektas M, Copley-Merriman C, Khan S, Sarda SP, Shammo JM. Paroxysmal nocturnal hemoglobinuria: patient journey and burden of disease. Journal of managed care & specialty pharmacy. 2020 Dec;26(12-b Suppl):S8-14.
  4. National PNH Service. Treatments [Internet]. pnhserviceuk.co.uk. [cited 2024 May 3]. Available from: https://pnhserviceuk.co.uk/patient-information/treatments/  Last accessed January 2025
  5. Hill, A., DeZern, A.E., Kinoshita, T. and Brodsky, R.A., 2017. Paroxysmal nocturnal haemoglobinuria. Nature reviews Disease primers 3(1), pp.1-14.
  6. Shah N, Bhatt H. Paroxysmal nocturnal hemoglobinuria. InStatPearls [Internet] 2023 Jul 31. StatPearls Publishing.
  7. Brodsky RA. Paroxysmal nocturnal hemoglobinuria. Blood, The Journal of the American Society of Hematology. 2014 Oct 30;124(18):2804-11.Schrezenmeier H, Muus P, Socié G, Szer J, Urbano-Ispizua A, Maciejewski JP et al. Baseline characteristics and disease burden in patients in the International Paroxysmal Nocturnal Hemoglobinuria Registry. haematologica. 2014 May;99(5):922.
  8. Schrezenmeier H, Röth A, Araten DJ, Kanakura Y, Larratt L, Shammo JM et al. Baseline clinical characteristics and disease burden in patients with paroxysmal nocturnal hemoglobinuria (PNH): updated analysis from the International PNH Registry. Annals of hematology. 2020 Jul;99:1505-14.
  9. Dingli D, Matos JE, Lehrhaupt K, Krishnan S, Yeh M, Fishman J et al. The burden of illness in patients with paroxysmal nocturnal hemoglobinuria receiving treatment with the C5-inhibitors eculizumab or ravulizumab: results from a US patient survey. Annals of hematology. 2022 Feb;101(2):251-63.
  10. Panse J, Sicre de Fontbrune F, Burmester P, Piggin M, Matos JE, Costantino H et al. The burden of illness of patients with paroxysmal nocturnal haemoglobinuria receiving C5 inhibitors in France, Germany and the United Kingdom: Patientreported insights on symptoms and quality of life. European Journal of Haematology. 2022 Oct;109(4):351-63.
  11. Peffault de Latour R, Röth A, Kulasekararaj AG, Han B, Scheinberg P, Maciejewski JP et al. Oral Iptacopan Monotherapy in Paroxysmal Nocturnal Hemoglobinuria. New England Journal of Medicine. 2024 Mar 14;390(11):994-1008.
  12. Cançado RD, Araújo AD, Sandes AF, Arrais C, Lobo CL, Figueiredo MS et al. Consensus statement for diagnosis and treatment of paroxysmal nocturnal haemoglobinuria. Hematology, transfusion and cell therapy. 2021 Oct 18;43:341-8.
  13. Schubart A, Anderson K, Mainolfi N, Sellner H, Ehara T, Adams CM et al. Small-molecule factor B inhibitor for the treatment of complement-mediated diseases. Proceedings of the National Academy of Sciences. 2019 Apr 16;116(16):7926-31.
  14. Barratt J, Rovin B, Zhang H, Kashihara N, Maes B, Rizk D et al. POS-546 efficacy and safety of iptacopan in IgA nephropathy: results of a randomized double-blind placebo-controlled phase 2 study at 6 months. Kidney international reports. 2022 Feb 1;7(2):S236.
  15. Rizk DV, Rovin BH, Zhang H, Kashihara N, Maes B, Trimarchi H et al. Targeting the alternative complement pathway with iptacopan to treat IgA nephropathy: design and rationale of the APPLAUSE-IgAN study. Kidney international reports. 2023 May 1;8(5):968-79.
  16. Fabhalta® (iptacopan) Summary of Product Characteristics. Available from https://www.medicines.org.uk/emc/product/15853/smpc
  17. Scottish population statistics. Available from: https://www.gov.scot/publications/building-new-scotland-migration-scotland-independence/pages/7/ Last accessed January 2025