Roche's PIASKY Approval: Major Competition Ahead For AstraZeneca & Pharma Giants

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disorder characterized by a trio of symptoms: intravascular hemolysis, thromboembolic events, and cytopenia. Due to the disease's variability, classifying it based on common presentations is difficult because each patient's experience can differ significantly. In 2023, the number of diagnosed PNH cases across the seven major markets (7MM) was approximately 12,000. This figure is expected to rise to around 13,000 by 2034, with the highest prevalence reported in the United States.

Before 2007, PNH was a severe condition with no effective treatments for hemolysis and thrombosis, leading to high mortality rates. However, the introduction of the anti-C5 agent eculizumab in the past decade marked a transformative change, significantly reducing hemolysis, decreasing the need for transfusions, and notably lowering the incidence of thrombosis.

Current disease-modifying treatments for PNH primarily involve complement inhibition therapy. The FDA-approved drugs SOLIRIS, ULTOMIRIS, and EMPAVELI are considered the gold standard. SOLIRIS was the first treatment for PNH, followed by ULTOMIRIS, both developed by Alexion Pharmaceuticals, offering critical C5 inhibition. Recently, new treatments such as factor B and D inhibitors have been approved, including FABHALTA (iptacopan) in the US and VOYDEYA (danicopan) in Japan, which are designed to provide enhanced efficacy with fewer side effects.

In June 2024, the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) endorsed crovalimab for the treatment of PNH in adults and adolescents aged 12 and older. This recommendation was based on the results of the global Phase III COMMODORE 2 clinical trial. In the US, the FDA approved crovalimab for PNH treatment in individuals aged 13 and up in June 2024, following the acceptance of its biologics license application in September 2023. The drug, marketed by Genentech (a Roche subsidiary), is now available in the US.

In Japan, Chugai Pharmaceutical filed a new drug application for PiaSky with the Ministry of Health, Labour, and Welfare (MHLW) in June 2023. PiaSky received approval in March 2024 and was launched in May 2024 for patients aged 12 and older with PNH. China's National Medical Products Administration (NMPA) approved crovalimab for PNH treatment in individuals aged 12 and up who have not previously received complement inhibitor therapy, following a priority review that started in August 2022. PiaSky is also under review by regulatory bodies in Europe and Taiwan

The market for paroxysmal nocturnal hemoglobinuria (PNH) is bustling with activity, with numerous companies competing in the field. New and innovative PNH treatments are on the horizon, such as Pozelimab (REGN3918) combined with Cemdisiran, OMS906, and NM8074 (ruxoprubart), showcasing a vibrant shift in therapeutic approaches.

Pozelimab is an innovative, fully human monoclonal antibody currently undergoing research. Its primary goal is to inhibit complement factor C5, which plays a role in red blood cell destruction (hemolysis) seen in conditions like Paroxysmal Nocturnal Hemoglobinuria (PNH) and other diseases influenced by the complement pathway. This IgG4 antibody binds strongly to both normal and variant forms of human C5, effectively blocking its activity.

In parallel, pozelimab is being tested in combination with Alnylam's cemdisiran, a siRNA that targets C5. This investigational combo aims to address a range of complement-related disorders, including PNH and myasthenia gravis. OMS-906, another promising candidate, is being developed for PNH, complement 3 glomerulopathy (C3G), idiopathic immune complex-mediated glomerulonephritis (ICGN), and arthritis. This monoclonal antibody targets mannan-binding lectin serine protease 3 (MASP-3) and can be administered either subcutaneously or intravenously.

The upcoming introduction of these novel therapies for paroxysmal nocturnal hemoglobinuria is set to revolutionize the market in the near future. As these advanced treatments progress through development and receive regulatory clearance, they are anticipated to redefine the standards of care for PNH, driving significant advancements in medical innovation and opening doors to economic growth.