Lebrikizumab

Japan-based Kyowa Kirin Co., Ltd and partner Amgen announced the discontinuation of all ongoing clinical trialsof rocatinlimab, an anti-OX40 monoclonal antibody that had reached late-stage development for moderate-to-severe atopic dermatitis, prurigo nodularis, and asthma. The companies announced the decision following a safety review that identified emerging malignancy cases with possible viral or immune-related links, including Kaposi’s sarcoma. According to the companies, the review identified one newly confirmed case and one suspected case of Kaposi’s sarcoma in addition to a previously confirmed case. While the overall number of malignancies observed across the clinical program remained below expected background incidence, the characteristics of the cases raised concerns that a biologically plausible risk could not be excluded. Kyowa Kirin and Amgen concluded that the potential safety risk may outweigh the benefits for patients in the studied indications. Rocatinlimab, previously designated AMG 451 by Amgen and KHK4083 by Kyowa Kirin, was designed as a fully human, non-fucosylated IgG1 antibody targeting the OX40 receptor on activated T cells. The molecule’s engineered Fc region enhances antibody-dependent cellular cytotoxicity (ADCC), enabling depletion of OX40-expressing pathogenic T cells in addition to blocking OX40 signaling. The therapeutic strategy aimed to rebalance immune responses in Th2-driven diseases such as atopic dermatitis, potentially delivering durable disease modification rather than temporary suppression of inflammatory cytokines. Phase III program halted despite positive efficacy results The decision halts the global ROCKET Phase III program, which comprised eight studies across multiple indications and geographic regions. Two pivotal atopic dermatitis trials had already reported positive top-line results before the safety signal emerged. The ROCKET HORIZON study (NCT05651711) met both co-primary endpoints—vIGA-AD 0/1 with at least a two-point reduction and EASI-75 at Week 24—as well as key secondary endpoints at the 300 mg subcutaneous dose. The ROCKET IGNITE trial (NCT05398445) also achieved its co-primary endpoints. Additional Phase III trials included (ROCKET BOOST) evaluating rocatinlimab with topical corticosteroids, ROCKET LAUNCH assessing alternative dosing regimens, an adolescent open-label study, and a long-term extension trial. Parallel development programs were underway in prurigo nodularis and asthma, all of which have now been terminated. Mechanistic concerns tied to viral-associated malignancy Kaposi’s sarcoma is caused by human herpesvirus-8 (HHV-8) and typically arises in settings of impaired immune surveillance. Because rocatinlimab was designed to deplete activated T cells through enhanced ADCC, the companies concluded that interference with antiviral immune responses represents a plausible mechanistic explanation for the observed signal. Neither company disclosed detailed safety datasets beyond the malignancy cases noted in the announcement. Both said they are notifying investigators and regulators and will conduct further analysis of the full clinical dataset. Development history Rocatinlimab’s development began with an early Phase I study in Japanese patients with atopic dermatitis around 2015. Subsequent Phase II studies—including a Phase IIb trial in atopic dermatitis initiated in 2018—demonstrated clinical efficacy and generated interest after data presented at the EADV Congress in 2021 suggested durable improvement after treatment cessation. In June 2021, Amgen and Kyowa Kirin entered a global collaboration agreement under which Amgen assumed sponsorship of the Phase III program while both companies retained commercialization rights. Kyowa Kirin said it will retain control of the rocatinlimab program, including regulatory filings and future commercialization decisions, although no development path has been outlined following the trial terminations. Implications for the OX40 pathway The discontinuation removes the most advanced OX40-targeted therapy from clinical development in inflammatory disease. The atopic dermatitis treatment landscape is already dominated by cytokine-targeted therapies such as dupilumab, tralokinumab, and lebrikizumab, alongside JAK inhibitors including abrocitinib and upadacitinib. Rocatinlimab had been differentiated by its upstream mechanism—targeting pathogenic T cells rather than individual cytokines. Its termination leaves no OX40-targeted therapy in late-stage development for inflammatory indications. Early-stage oncology programs involving OX40 agonists, designed to stimulate T-cell responses rather than suppress them, remain in development and are not directly affected by the findings. Leave a Reply Cancel reply Your email address will not be published. Required fields are marked * Comment * Name * Email * Website

Dive Brief:Eli Lilly inked another deal in the anti-inflammatory space, agreeing to pay CSL Ltd. $100 million to license a monoclonal antibody that targets interleukin-6 (IL-6).Under the agreement announced Wednesday, CSL will retain rights to develop the drug, clazakizumab, to prevent cardiovascular complications in patients with end-stage kidney disease. The Australian company is currently testing the drug for that use in a Phase 3 trial.Indianapolis-based Lilly will develop the medicine for other indications. As part of the deal, CSL is eligible for royalties as well as payments for reaching certain clinical, regulatory and commercial milestones.Dive Insight:Flush with cash from its best-selling obesity and diabetes drug franchise, Lilly has actively looked outside to beef up its pipeline in recent years. Already this year, the company has inked agreements to buy the biotechnology startup Orna Therapeutics for as much as $2.4 billion and Ventyx Biosciences for $1.2 billion to gain a drug that may treat a variety of immunological conditions.Those deals followed the $3 billion buyout of Morphic Therapeutics in 2024 and a $1.1 billion purchase of Dermira in 2020. The Dermira takeover gave Lilly a different interleukin inhibitor, one that targets IL-13. Lilly now sells the medication as Ebglyss to treat eczema.Clazakizumab was originally developed by Vitaeris, which CSL acquired in 2020. Its designed to stop the overproduction of the cytokine IL-6 to reduce inflammation and the progression of a range of diseases. CSLs development of the drug included a study to see if it could help prevent rejection and organ failure in kidney transplant patients, Fierce Biotech reported earlier. That trial ended early for lack of efficacy.There is an established track record for medicines that target IL-6, however. Roches Genentech sells the IL-6 receptor antagonist Actemra for a range of inflammatory conditions, including rheumatoid arthritis and a form of interstitial lung disease. Sanofi and Regeneron also have an IL-6 drug called Kevzara that originally won U.S. approval in 2017 to treat rheumatoid arthritis. '