Crovalimab, monthly injection therapy, up for approval in Japan

Data from COMMODORE studies supporting this request, with others likely

Marisa Wexler MS avatar

by Marisa Wexler MS |

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Chugai Pharmaceutical has applied to regulatory authorities in Japan seeking the approval of crovalimab, an under-the-skin injection therapy that can be administered at home, to treat paroxysmal nocturnal hemoglobinuria (PNH).

“We are very pleased that crovalimab, our in-house developed project, has been submitted for regulatory approval in Japan for the indication of paroxysmal nocturnal hemoglobinuria,” Osamu Okuda, president and CEO of Chugai, a member of the Roche group, said in a company press release. Chugai is developing crovalimab alongside Roche and its subsidiary Genentech.

“With the option for subcutaneous [under-the-skin] self-administration, crovalimab could help meet the lifelong needs of people living with PNH and their caregivers,” Levi Garraway, MD, PhD, chief medical officer and head of global product development at Genentech, said in a press release from that company.

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“We will continue to work with Roche towards global filing for this drug so that the benefits of crovalimab can be delivered as soon as possible to patients and caregivers who are waiting for this new treatment,” Okuda said in a separate press release.

Chugai’s application is supported in part by data from the Phase 3 COMMODORE 2 trial (NCT04434092), which tested crovalimab against Soliris (eculizumab), an approved PNH treatment.

In PNH, blood cells are made lacking certain proteins on their surface, leading to the abnormal activation of a part of the immune system called the complement cascade, which ultimately results in their destruction (hemolysis).

Soliris, marketed by AstraZeneca, works to block the activation of the complement cascade by binding to a complement protein called C5. It’s given via an infusion into the bloodstream every two weeks. AstraZeneca also markets another C5-targeting therapy, Ultomiris (ravulizumab), that’s given via into-the-vein infusion every one or two months or as a once weekly subcutaneous injection.

Similar to Soliris and Ultomiris, crovalimab is designed to stop complement activation by targeting the C5 protein, though it specifically binds to a different part of the protein. Unlike Soliris and Ultomiris, crovalimab is designed to be administered via an under-the-skin injection once each month. This mode of administration is similar to that of the approved PNH therapy Empaveli (pegcetacoplan), though Empaveli targets a different complement protein, called C3.

“Anti-C5 inhibitors are defined as a standard of care in PNH, and subcutaneous crovalimab aims to bring new values,” Okuda said.

The COMMODORE 2 study enrolled 204 adults not previously on a C5-targeting therapy. Participants were randomly assigned to receive either Soliris or crovalimab for about six months.

The study’s main goals assessed the percentage of patients who did not need blood transfusions over the entire study, as well as the proportion who achieved hemolysis control from week five to week 25, when participants were on a stable maintenance treatment.

Similar proportions of patients free of transfusions, achieving hemolysis control

Study results were shared at the European Hematology Association (EHA) Hybrid Congress, held earlier this month in Frankfurt, Germany.

Findings showed the proportion of transfusion-free patients was similar in the crovalimab (65.7%) and Soliris (68.1%) treatment groups, the companies reported. The proportion of patients with hemolysis control from week five to week 25 also was comparable: 79.3% with crovalimab and 79% with Soliris.

Both treatments led to clinically significant reductions in fatigue, as measured by changes in the FACIT-Fatigue score. Fatigue score improvement was numerically higher with crovalimab (mean change of 7.8 points) compared with Soliris (mean change of 5.2 points), though this difference was not considered statistically significant.

Adverse events — treatment side effects and other safety-related issues — were reported in about four out of five patients in both treatment groups. An “infusion-related” reaction was reported to be the most common side effect in both groups (16% with crovalimab and 13% with Soliris), and one participant in each group discontinued treatment due to side effects.

Serious infections, which are a potential risk of any therapy that suppresses the immune system, occurred in 3% of patients treated with crovalimab and in 7% of those given Soliris.

“A subcutaneous administration once every four weeks of crovalimab in the maintenance phase demonstrated favorable efficacy and safety, bringing a new treatment option possibly decreasing the treatment burden on patients, such as reducing the dosing time,” Okuda said.

Chugai’s application in Japan also is supported by data from another Phase 3 study, called COMMODORE 1 (NCT04432584), an open-label trial of crovalimab in patients switching from other complement-blocking therapies. Findings from the ongoing study, enrolling eligible patients at sites across the U.S., Europe, and elsewhere, have suggested that disease activity generally remained stable after patients switched to crovalimab.

“Data from the COMMODORE studies will be submitted to regulatory authorities around the world,” Garraway said.