Adults in England and Wales with rare blood disorder to get access to new oral monotherapy on NHS

• The National Institute for Health and Care Excellence (NICE) has published final guidance (TA number 1000) recommending Fabhalta®▼(iptacopan) as a treatment option in eligible patients on the NHS in England and Wales. Specific funding arrangements in both countries enables access to iptacopan from today, 4 September.
• The reimbursement decision is in line with the licence, granted in August by the Medicines and Healthcare products Regulatory Agency (MHRA), as a monotherapy for adults with paroxysmal nocturnal haemoglobinuria (PNH) who have haemolytic anaemia.
• Iptacopan is the first oral monotherapy for the treatment of PNH, increasing treatment options available for patients and clinicians, who until now have relied on infusions as the standard of care.
• Over 950 people live with PNH in England and Wales. The symptoms of PNH may be burdensome and can 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

London, 4 September 2024 - Today, Novartis announced that the National Institute for Health and Care Excellence (NICE) has published final technology appraisal guidance, recommending Fabhalta®▼ (iptacopan) for use on the NHS in England and Wales as an option for treating paroxysmal nocturnal haemoglobinuria (PNH) in adults with haemolytic anaemia.

The announcement follows last month’s decision from the MHRA to grant marketing authorisation for iptacopan in Great Britain. The approval from NICE covers the full patient population of the MHRA licence.

Iptacopan will be available to eligible patients in England and Wales immediately. In England, funding to deliver this is initially being provided by the interim Innovative Medicines Fund, while in Wales iptacopan will be routinely commissioned as per the Access to medicines for patients in Wales policy.

PNH is an ultra-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 PNH patients experience fatigue caused by anaemia, having a direct impact on quality of life and means they can also require blood transfusions.3,4,8-10

Responding to the announcement, patient expert Louise Peacock said: “PNH is hugely disruptive to patients and means they struggle to feel in control of their day-to-day lives. The risk of infection and a possible life-threatening crisis create an additional layer of anxiety for many – including myself. As well as the logistical challenges involved with managing the disease, quality of life remains poor for many and it’s very reassuring to see another treatment option become available on the NHS and hopefully help to transform lives.”

The licensing and routine funding decisions were 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 residual 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.

Austin Kulasekararaj, Consultant Haematologist at King’s College Hospital said, “Data from the APPLY-PNH and APPOINT-PNH trials showed that iptacopan can be effective in controlling haemolysis and improving haemoglobin levels in patients with PNH. Today’s news means our world leading National PNH service now has access to the first oral treatment option for this rare disease.”

In both trials, iptacopan was generally well tolerated. There were no deaths, and no patients stopped treatment or interrupted treatment due to adverse events (side effects) in either trial.11

“Today’s announcement shows how Novartis can work with partners across the healthcare system to deliver meaningful solutions for patients most in need,” said Marie-Andrée Gamache, Country President Novartis UK and Ireland. “In securing access for eligible patients to the first oral monotherapy to become available in PNH, we are again demonstrating our commitment to UK life sciences and to improving the lives of those living with 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.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.14,15 200 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 are asked to report any suspected adverse reactions. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard.

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 LinkedIn, Facebook, and Instagram.

References

1. National PNH Service. Annual Report [Internet]. pnhserviceuk.co.uk. [cited 2024 May 3]. Available from: https://pnhserviceuk.co.uk/healthcare-professionals/annual-report/

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/

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: Patient-reported 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. 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.

15. Fabhalta® (iptacopan) Summary of Product Characteristics. Available from https://www.ema.europa.eu/en/documents/product-information/fabhalta-epar-product-information_en.pdf. August 2024