Roche’s PiaSky approved in the EU as the first monthly subcutaneous treatment for people with PNH

• With the option to self-administer, PiaSky® (crovalimab) has the potential to reduce treatment burden for people with paroxysmal nocturnal haemoglobinuria (PNH) in Europe and their caregivers
• Approval is based on COMMODORE 2, where subcutaneous (SC) PiaSky once a month was equivalent to intravenous eculizumab every two weeks^1,2
• PiaSky advances C5 inhibitionthrough innovative recycling technology, which enables its monthly SC administration³
  

Basel, 27 August 2024 - Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today that the European Commission has approved PiaSky® (crovalimab), a novel recycling monoclonal antibody that inhibits the complement protein C5, for adults and adolescents (12 years of age or older with a weight of 40 kg and above) with paroxysmal nocturnal haemoglobinuria (PNH) who are either new to, or have been previously treated with C5 inhibitors. PNH is a rare and life-threatening blood condition where red blood cells are destroyed by the complement system – part of the innate immune system – causing symptoms such as anaemia, fatigue and blood clots, and potentially leading to kidney disease.⁴

“People with PNH are often burdened with life-long, frequent intravenous infusions with time-consuming clinic visits, meaning that their lives, as well as their caregivers’ and families’ lives, may revolve around the demands of their treatment,” said Prof. Alexander Röth, M.D., Head of Classical Haematology and Haemostasis at the West German Cancer Centre, University Hospital Essen, Germany. “More flexible treatment options such as PiaSky, which are just as effective but less frequent and can be given more quickly at home, are essential to give people with PNH greater control over their treatment and more independence.”

PiaSky is the first monthly subcutaneous (SC) treatment for PNH in the European Union, with the option to self-administer following adequate training. It provides an alternative option to current C5 inhibitors that require regular intravenous infusions, which could help to reduce treatment burden and disruption to the lives of people with PNH and their caregivers.³

“The PiaSky approval brings a new option to the PNH treatment landscape, combining the disease control achievable through C5 inhibition with a cutting-edge recycling technology that enables monthly subcutaneous administration,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. “We are pleased to bring this new treatment to people with PNH in Europe with the hope it may lessen the treatment burden faced by many living with this condition.” 

C5 inhibitors – treatments that block part of the complement system cascade – have been shown to be effective in treating PNH.⁵ PiaSky has been developed to address the needs of people living with PNH and some of the challenges that accompany these existing treatment options. It advances complement inhibition through its innovative recycling technology, which enables monthly SC administration by allowing the medicine to bind and inhibit the C5 protein multiple times and to act longer in the body with a small volume of medicine.^1,3

This approval is based on the results from the Phase III COMMODORE 2 study in people with PNH who have not been previously treated with C5 inhibitors. The study demonstrated that PiaSky, administered as SC injections every four weeks, achieved disease control and was well-tolerated. PiaSky was non-inferior with comparable safety to eculizumab, an existing standard of care C5 inhibitor, given intravenously every two weeks. The rate of adverse events in people treated with PiaSky was similar to treatment with eculizumab.^1,2 The application included supportive data from two additional Phase III studies, the COMMODORE 1 study, in people with PNH switching from currently approved C5 inhibitors, and the COMMODORE 3 study in people new to C5 inhibitor treatment in China.^1,2,6-8

PiaSky is the first monthly SC treatment for PNH, approved in multiple territories around the world, including the US and Japan, based on results of the COMMODORE studies. It is being investigated in a broad clinical development programme, including five Phase III studies and three earlier phase studies in complement-mediated diseases, including PNH, atypical haemolytic uremic syndrome and sickle cell disease.^2,6,8-13

About PiaSky® (crovalimab)
PiaSky® (crovalimab) is a novel recycling monoclonal antibody that inhibits the complement protein C5 and is designed to block the complement system – a vital part of the innate immune system that acts as the body’s first line of defence against infection. PiaSky has been engineered by Chugai Pharmaceutical Co., Ltd, to address the needs of people living with complement-mediated diseases. It provides patients with a potential for subcutaneous (SC) self-administration following adequate training, an initial intravenous infusion and weekly SC loading doses in the first month of treatment.^1,3

PiaSky works by binding to C5, blocking the last step of the complement cascade and delivering rapid and sustained complement inhibition. It is also recycled within the bloodstream, enabling small volume SC administration every four weeks. In addition, PiaSky binds to a different C5 binding site from current treatments, which has the potential to provide a treatment option for people with specific C5 gene mutations who do not respond to current therapies.^1,3

About the COMMODORE 2 study
The COMMODORE 2 study is a Phase III, randomised, open-label study evaluating the efficacy and safety of PiaSky® (crovalimab) versus eculizumab in people with paroxysmal nocturnal haemoglobinuria who have not been treated previously with C5 inhibitors. The study’s co-primary efficacy endpoints measure transfusion avoidance and control of haemolysis (the ongoing destruction of red blood cells measured by lactate dehydrogenase levels). The adults enrolled in the study were randomised in a 2:1 ratio to be treated with either subcutaneous (SC) PiaSky every four weeks or intravenous eculizumab every two weeks. The participants who were less than 18 years old were included in a non-randomised treatment arm and were treated with SC PiaSky every four weeks.^1,2

About Roche
Founded in 1896 in Basel, Switzerland, as one of the first industrial manufacturers of branded medicines, Roche has grown into the world’s largest biotechnology company and the global leader in in-vitro diagnostics. The company pursues scientific excellence to discover and develop medicines and diagnostics for improving and saving the lives of people around the world. We are a pioneer in personalised healthcare and want to further transform how healthcare is delivered to have an even greater impact. To provide the best care for each person we partner with many stakeholders and combine our strengths in Diagnostics and Pharma with data insights from the clinical practice.

In recognising our endeavour to pursue a long-term perspective in all we do, Roche has been named one of the most sustainable companies in the pharmaceuticals industry by the Dow Jones Sustainability Indices for the fifteenth consecutive year. This distinction also reflects our efforts to improve access to healthcare together with local partners in every country we work.

Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan.

For more information, please visit www.roche.com.

All trademarks used or mentioned in this release are protected by law.

References
[1] Roth A, et al. The Phase III, Randomised COMMODORE 2 Trial: Results from a Multicentre Study of Crovalimab vs Eculizumab in Paroxysmal Nocturnal Hemoglobinuria (PNH) Patients Naïve to Complement Inhibitors. Presentation at European Hematology Association (EHA) Annual Congress; 2023 June 08-13. Abstract #S181.
[2] COMMODORE 2 (NCT04434092). [Internet; cited August 2024] Available at: https://www.clinicaltrials.gov/ct2/show/NCT04434092.
[3] Fukuzawa T, et al. Long lasting neutralisation of C5 by SKY59, a novel recycling antibody, is a potential therapy for complement-mediated diseases. 2017; Sci Rep 7, 1080.
[4] National Organization for Rare Diseases. Paroxysmal nocturnal hemoglobinuria. [Internet; cited August 2024]. Available at: https://rarediseases.org/rare-diseases/paroxysmal-nocturnal-hemoglobinuria/.
[5] Peffault de Latour R, et al. Hemolytic paroxysmal nocturnal hemoglobinuria: 20 years of medical progress. Seminars in Hematology. 2022;59(1):38-46
[6] Scheinberg P, et al. Phase III Randomised, Multicentre, Open-Label COMMODORE 1 Trial: Comparison of Crovalimab Vs Eculizumab in Complement Inhibitor-Experienced Patients with Paroxysmal Nocturnal Hemogobinuria (PNH). Presentation at European Hepatology Association (EHA) Annual Congress; 2023 June 08-13. Abstract #S183.
[7] COMMODORE 1 (NCT04432584). [Internet; cited August 2024] Available at:https://www.clinicaltrials.gov/ct2/show/NCT04432584.
[8] Liu H, et al. Six-month Crovalimab Extension in the Phase III COMMODORE 3 Study: Updated Efficacy and Safety Results in Complement Inhibitor-Naive Patients with Paroxysmal Nocturnal Hemoglobinuria. Poster presentation at European Hematology Association (EHA) Annual Congress; 2023 June 08-13. Abstract #P785.
[9] COMMUTE-p (NCT04958265). [Internet; cited August 2024] Available at: https://www.clinicaltrials.gov/ct2/show/NCT04958265.
[10] COMMUTE-a (NCT04861259). [Internet; cited August 2024] Available at:https://www.clinicaltrials.gov/ct2/show/NCT04861259.
[11] Nishimura J, et al. Crovalimab for Treatment of Patients With Paroxysmal Nocturnal Hemoglobinuria And Complement C5 Polymorphism – Experience From The Composer Phase I/II Study. EHA Library. 2020; Abstract #PB1992.
[12] CROSSWALK-a (NCT04912869). [Internet; cited August 2024]. Available at: https://clinicaltrials.gov/ct2/show/NCT04912869.
[13] CROSSWALK-c (NCT05075824). [Internet; cited August 2024]. Available at:https://clinicaltrials.gov/ct2/show/NCT05075824.

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