HIGH IMPACT – Roche announced positive results from its COMMODORE1 and 2 studies of crovalimab in PNH patients.

  • COMMODORE2 (naïve study) met co-primary endpoint of transfusion avoidance and control of hemolysis (LDH). Crovalimab was non-inferior to eculizumab.
  • COMMODORE1 (switch study) efficacy and safety data supported a favorable benefit-risk profile of crovalimab.
  • Based on these results Roche will file for crovalimab globally. Chugai in a separate press release also confirmed plans for filing in Japan.
  • No further details of the data were provided. Details will be presented at an upcoming meeting, likely EHA in June 2023

inThought Analysis

  • With these positive results,  crovalimab will likely get approval in US around mid-2024
  • Recall that COMMODORE1 primary outcome was changed from control of LDH to safety last year, but secondary outcomes still measure efficacy in patients switching from eculizumab. Both studies had a non-randomized arm with patients <18 yrs and COMMODORE1 also included patients who were on off-label doses of eculizumab (higher than 900mg and/or more frequently than Q2W), those on ravulizumab and those with known mutations in C5 gene. Roche is therefore likely to receive a broad label for crovalimab in PNH.
  • We will need to see the detailed data from COMMODORE1 to determine whether patients switching from eculizumab to crovalimab are able to maintain disease control. Although likely not powered to show non-inferiority, it will also be important to see whether the efficacy is similar to Ultomiris.
  • Given similar efficacy, the availability of crovalimab will split the C5i market between once monthly SC (crovalimab), once weekly SC (Ultomiris SC), once every 2w IV (Soliris), or once every 8w IV (Ultomiris).
  • Since most patients in the US and EU5 have already been switched from Soliris to Ultomiris, physicians will be keen to see the results in patients who were switched from Ultomiris to crovalimab. Recall that while Ultomiris had shown non-inferiority to Soliris in its registrational trials, numerically it performed better than Soliris with better control of intravascular hemolysis. With iptacopan entering the market, patients who are considering switching from Soliris/Ultomiris are likely to opt for an oral therapy. Additionally, crovalimab will likely be under pricing pressure soon after its launch with biosimilars expected to hit the US market in 1Q 2025 and even earlier in EU.
  • Crovalimab’s main opportunity lies in geographies where Soliris and Ultomiris have not been approved yet. Hence Roche’s strategy to file in China first with approval expected in mid-2023. However, even there it was narrowly beaten with Soliris winning approval earlier this year. An at home once monthly SC administration will still remain a significant advantage to Soliris.

Source: Roche Press Release, Chugai Press Release