Rocatinlimab

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

Kyowa Kirin and Amgen are working to alert trial investigators and regulators, with plans to terminate all studies after patients are followed up with.\n Two new cancer cases have prompted Kyowa Kirin to shutter all clinical studies of its investigational anti-OX40 monoclonal antibody designed to treat inflammatory diseases.The discontinuation will likely disrupt the Japanese company’s previously stated plan to request FDA approval of the asset in atopic dermatitis in the first half of this year. “This matter does not constitute an immediate determination to discontinue the entire rocatinlimab development program,” a Kyowa spokesperson told Fierce. “However, at this point in time, we consider the likelihood of continuing development or resuming clinical trials to be extremely low.”News of the shuttered studies comes about a month after Amgen abandoned a pact with Kyowa centered around the candidate, dubbed rocatinlimab. A recent safety review of rocatinlimab found “emerging concerns of malignancies with possible viral or immune-related links,” according to a March 3 release from Kyowa.One new confirmed case and an additional suspected case of Kaposi sarcoma—a soft tissue cancer—were reported on top of another previously recorded case. The identified cancers indicate a “potential mechanistic link to OX40 pathway modulation,” according to the company.“Based on this update, both Kyowa Kirin and Amgen have concluded that the potential risks may outweigh the benefits for the studied patient populations,” the release reads.The two pharmas are working to alert trial investigators and regulators, with plans to terminate all studies after patients are followed up with.The collaborators had been testing out rocatinlimab in a vast R&D program, running eight phase 3 trials in atopic dermatitis alone. The anti-OX40 asset was also being evaluated in a late-stage study for prurigo nodularis, a chronic skin condition characterized by itchy bumps. Additionally, rocatinlimab was being studied in moderate to severe uncontrolled asthma, with a midstage trial readout expected this year.Back in 2021, Amgen paid $400 million to align with Kyowa on the program, offering the Japan-based pharma up to $850 million in potential milestone payments.But, earlier this year, Amgen walked away from the partnership. At the time, Kyowa attributed the decision to Amgen’s strategic portfolio prioritization.In its most recent release, Kyowa said the safety review was “conducted over the last several weeks,” so it is unclear whether Amgen was aware of these findings before terminating the deal at the end of January.  The California pharma’s decision may have been made on the strength of the data alone. In a late-stage study, rocatinlimab beat placebo as a treatment for atopic dermatitis, but questions remained about the asset’s positioning in a competitive space. Unfavorable comparisons to Sanofi and Regeneron’s juggernaut Dupixent prompted William Blair analysts to forecast “a moderate commercial opportunity” for rocatinlimab as a later-line therapy.Now, the two companies aim to analyze the full rocatinlimab dataset and pledged to share more information once those assessments are done. “The overall number of malignancy cases across the program remains below expected background rates,” Kyowa noted.Editor\'s note: This article was updated at 11:21 a.m. ET on March 3 to include comment from Kyowa.