Roche's PiaSky (crovalimab) has received approval from the European Commission, marking a significant milestone as the first therapy for the rare blood disorder paroxysmal nocturnal haemoglobinuria (PNH) that can be administered via monthly subcutaneous injection in the EU. The anti-complement C5 antibody has now secured regulatory clearance in the world's top four pharmaceutical markets, following earlier approvals in China, Japan, and the United States.
Addressing Treatment Burden in Rare Disease
The approval represents a potential paradigm shift for PNH patients, who currently require regular clinic visits for intravenous infusions. PiaSky can be self-administered by patients at home following appropriate training, potentially reducing the treatment burden associated with existing therapies. This convenience factor differentiates it from established competitors including AstraZeneca's Soliris (eculizumab), which requires dosing every two weeks, and Ultomiris (ravulizumab), which needs infusion every eight weeks.
The competitive landscape shows mixed performance for existing therapies. Soliris, nearing patent expiration, experienced a 14% sales decline to $700 million in the second quarter, while Ultomiris demonstrated strong growth of 36% to $946 million. Apellis' C3 inhibitor Empaveli (pegcetacoplan), though also administered subcutaneously, remains a minor market player with sales below $25 million in the second quarter.
Clinical Evidence and Mechanism
The European approval is supported by data from the COMMODORE 2 trial, which demonstrated that subcutaneous PiaSky administered once monthly was equivalent to intravenous Soliris given every two weeks in controlling haemolysis - the characteristic destruction of red blood cells in PNH. The study also showed reduced need for blood transfusions among treated patients.
Crovalimab's unique engineering allows it to bind repeatedly to its target antigen, unlike typical antibodies that bind only once. This design enables sustained complement inhibition at lower doses, according to the company's technical specifications.
"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," stated Roche's chief medical officer, Levi Garraway.
Emerging Market Competition
The PNH treatment landscape faces significant disruption from new oral therapies approaching market entry. Novartis' recently approved Fabhalta (iptacopan), a targeted factor B inhibitor, has demonstrated superior performance compared to Soliris and Ultomiris in PNH patients experiencing residual anaemia. Jefferies analysts project Fabhalta could achieve $3.6 billion in peak annual sales across multiple indications.
AstraZeneca's oral Factor D inhibitor Voydeya (danicopan) has also entered the market as an add-on therapy for patients who don't adequately respond to C5 inhibitor monotherapy.
Pipeline Expansion Beyond PNH
While PiaSky's commercial potential in PNH remains unclear with no available sales figures, Roche indicated in its second-quarter results that the drug's greatest opportunity may lie in other indications. The company is conducting phase 2 testing in sickle cell disease, with a phase 3 trial readout expected in atypical haemolytic uraemic syndrome (aHUS). However, the company appears to have discontinued its lupus nephritis program, as it no longer appears in Roche's pipeline listings.
The approval positions PiaSky to compete across multiple complement-mediated disorders, though it will face established competition from Soliris and Ultomiris in aHUS, with potential future competition from Fabhalta, which is also in clinical development for that indication.
