Medicines and Healthcare Products Regulatory Authority (MHRA) issues Great Britain Marketing Authorisation for Aspaveli®▼ (pegcetacoplan) in adults with paroxysmal nocturnal haemoglobinuria

Medicines and Healthcare Products Regulatory Authority (MHRA) issues Great Britain Marketing Authorisation for Aspaveli®▼ (pegcetacoplan) in adults with paroxysmal nocturnal haemoglobinuria

Sobi in the UK has today announced that the Medicines and Healthcare Products Regulatory Authority (MHRA) has authorised Aspaveli® (pegcetacoplan) in the United Kingdom as an orphan medicinal product.[i] Aspaveli is indicated for adult patients with paroxysmal nocturnal haemoglobinuria (PNH) who are anaemic after treatment with a C5 inhibitor for at least three months. Following the issuing of the Marketing Authorisation, it is anticipated that the National Institute of Health and Care Excellence (NICE) will issue its final guidance for the treatment recommending its use for as per the terms of its licence. NICE previously issued a draft Final Appraisal Document (FAD) on 8 December 2021 following a Fast Track Appraisal.^[ii]

• PNH is a rare, chronic, life-threatening blood disorder, affecting approximately 650 – 900 people in England.^[iii] As such, Aspaveli has also been recognised by the MHRA as a Designated Orphan Drug
• Characterised by persistently low haemoglobin, PNH can result in frequent blood transfusions and debilitating symptoms such as severe fatigue (96% of cases[iv]) and anaemia (88% of cases[v]). If left untreated, it has a 10-year mortality rate of 29%[vi], with 40-67% of deaths caused by thrombosis[vii]
• Despite improvements in haemolytic activity with C5 inhibitor treatment, patients can still experience a substantial life-limiting and debilitating burden of illness^[viii], with approximately 72% of C5-treated patients remaining anaemic.[ix] Around a quarter (20 – 36%) also remain transfusion-dependent^9,[x]^,[xi]^,[xii]
• Living with the symptoms of PNH, such as fatigue and anaemia, can have a significant impact on quality of life.⁸  Over a third of patients (37.5%) report PNH as causing impairment in normal daily activities and over a quarter (26.7%) report PNH as causing impairment at work[xiii]

“Pegcetacoplan is a valuable step forward in treatment for patients with PNH.  Despite recent treatment advances, some patients with PNH who are being treated with the current standard of care experience low haemoglobin levels and extravascular haemolysis, causing anaemia and fatigue.  This adversely affects their quality of life and can lead to blood transfusion requirement” said Dr Morag Griffin, Consultant Haematologist at Leeds Teaching Hospitals NHS Trust. “Pegcetacoplan has demonstrated clinically meaningful improvements in key markers of disease in patients with PNH, and therefore presents an important new therapeutic option.”

“Pegcetacoplan, in clinical trials has proven to improve anaemia and manage ongoing haemolysis for patients with PNH.  The subcutaneous self-administered infusion of pegcetacoplan also provides patients with alternative modality of treatment, addressing an unmet need in PNH for those with limited venous access.” said Dr Richard Kelly, Consultant Haematologist at Leeds Teaching Hospitals NHS Trust.

“This is a landmark moment for people who are affected by PNH in the UK that  are in need of new treatments” said Michael Oliver, General Manager at Sobi UK & Republic of Ireland.  “Many people with PNH suffer from anaemia, fatigue, and impaired quality of life.  The licensing of pegcetacoplan provides a different treatment option, which may help to alleviate this disease burden.”

About the PEGASUS study
PEGASUS (APL2-302; NCT03500549) was an open label, randomised, active comparator controlled 16 week Phase 3 study in 80 adults (≥18 years of age) in whom PNH was diagnosed by high-sensitivity flow cytometry and who had haemoglobin levels of less than 10.5 g per deciliter and treated with a stable dose of eculizumab for at least the previous 3 months. The objective of this study was to establish the efficacy and safety of Aspaveli® (pegcetacoplan) in these patients compared to eculizumab.

Aspaveli was significantly superior to eculizumab for the primary endpoint for the haemoglobin change from baseline.  Non-inferiority was demonstrated in key secondary endpoints of transfusion avoidance and change from baseline in Absolute reticulocyte count versus eculizumab.[xiv]  Non-inferiority was not met in change from baseline in LDH.  Due to hierarchical testing, statistical testing for change from baseline for FACIT-Fatigue score was not formally tested.  However, the improvement in FACIT-fatigue score was clinically meaningful versus eculizumab.¹⁴

The most commonly reported adverse reactions in patients treated with ASPAVELI were injection site reactions: injection site erythema, injection site pruritus, injection site swelling, injection site pain. Other adverse reactions reported in more than 10% of patients during clinical studies were upper respiratory tract infection, abdominal pain, diarrhoea, headache, fatigue, and pyrexia. The most commonly reported serious adverse reactions were haemolysis and thrombocytopenia.[xv]

Aspaveli®/Empaveli® (pegcetacoplan)

Pegcetacoplan is a targeted C3 therapy designed to regulate excessive activation of the complement cascade, a part of  the body’s immune system, which can lead to the onset and progression of many serious diseases. Pegcetacoplan is under investigation for several rare diseases across haematology, nephrology, and neurology. Pegcetacoplan is authorised for the treatment of paroxysmal nocturnal haemoglobinuria (PNH) in the European Union as Aspaveli® and in the United States, Australia, and Saudi Arabia as Empaveli®.  Aspaveli has also been submitted for health technology assessment in Scotland.

About the Sobi and Apellis Collaboration

Sobi and Apellis have global co-development rights for systemic pegcetacoplan. Sobi has exclusive ex-US commercialisation rights for systemic pegcetacoplan, and Apellis has exclusive US commercialisation rights for systemic pegcetacoplan and retains worldwide commercial rights for ophthalmological pegcetacoplan, including for geographic atrophy (GA).

About Sobi®

Sobi is a specialised international biopharmaceutical company transforming the lives of people with rare diseases. Providing sustainable access to innovative medicines in the areas of haematology, immunology and specialty care, Sobi has approximately 1,600 employees across Europe, North America, the Middle East and Asia. In 2021, revenue amounted to SEK 15.5 billion. You can find more information about Sobi in the UK and the Republic of  Ireland at www.sobi-uk.co.uk

Contact

Madeleine Harris Smith, Patient Advocacy and Communications Manager
+44 (0) 7443 191 726
madeleine.harrissmith@sobi.com

[i]  Aspaveli (pegcetacoplan) MHRA marekting authorisation - PLGB 30941/0022 - 0001

[ii] National Institute for Health and Care Excellence. (2021). Single Technology Appraisal – Pegcetacoplan for treating paroxysmal nocturnal haemoglobinuria – Final Appraisal Document. Available at: https://www.nice.org.uk/guidance/gid-ta10651/documents/final-appraisal-determination-document (accessed Feburary 2022)

[iii] National Institute for Health and Care Excellence. (2021). Single Technology Appraisal – Pegcetacoplan for treating paroxysmal nocturnal haemoglobinuria – Final Scope. Available at: https://www.nice.org.uk/guidance/gid-ta10651/documents/final-scope (accessed Feburary 2022)

[iv] Meyers, G., et al. (2007). Disease-Related Symptoms Reported across a Broad Population of Patients with Paroxysmal Nocturnal Hemoglobinuria. Blood; 110 (11): Abstract 3683.

[v] Nishimura, J-I., et al. (2004). Clinical Course and Flow Cytometric Analysis of Paroxysmal Nocturnal Hemoglobinuria in the United States and Japan. Medicine; 83 (3) :193-207.

[vi] Bektas M, Copley-Merriman C, Khan S, Sarda SP, Shammo JM. Paroxysmal nocturnal hemoglobinuria: role of the complement system, pathogenesis, and pathophysiology. J Manag Care Spec Pharm. 2020 Dec;26(12-b Suppl):S3-S8

[vii] Hill, A., et al. (2013).  Thrombosis in paroxysmal nocturnal hemoglobinuria. Blood; 121 (25).

[viii] Dingli, D., et al. (2020) Work Productivity Loss and Quality of Life in Paroxysmal Nocturnal Hemoglobinuria Among Patients Receiving C5 Inhibitors in the United States. Blood; 136 (1):

[ix] McKinley C. Extravascular Hemolysis Due to C3-Loading in Patients with PNH Treated with Eculizumab: Defining the Clinical Syndrome. Blood. 2017;130:3471.

[x] Risitano, A.M., Marotta, S., Ricci, P., et al. (2019). Anti-complement Treatment for Paroxysmal Nocturnal Hemoglobinuria: Time for Proximal Complement Inhibition? A Position Paper From the SAAWP of the EBMT. Front Immunol;10: 1157.

[xi] Dingli, D. et al (2020) Clinical Burden of Paroxysmal nocturnal hemoglobinuria among patients receiving c5 inhibitors in the United States

[xii] Luzzato L. Recent advances in the pathogenesis and treatment of paroxysmal nocturnal hemoglobinuria. F1000Res 2016; 5:F1000 Faculty Rev-209

[xiii] Panse, J. et al. (2021). Paroxysmal Nocturanl Hemoglobinuria’s Humanistic And Economic Burden In Patients Receiving C5 Inhibitors In Europe.

[xiv] Hillmen, P et al. (2021) Pegcetacoplan versus Eculizumab in Paroxysmal Nocturnal Hemoglobinuria. N Engl J Med 2021; 384:1028-1037

[xv] Aspaveli (2022) Summary of Product Characteristics