Amgen has shared (PDF) the first phase 3 data on its $400 million eczema drug, linking the anti-OX40 antibody to significant improvements in symptoms. But, while the trial met its primary endpoints, the biotech still needs to make the case that there is a role for rocatinlimab in a market served by Dupixent.
The HORIZON trial randomized 726 people with moderate to severe atopic dermatitis, a form of eczema, to receive rocatinlimab or placebo. After 24 weeks, 32.8% of people taking rocatinlimab had experienced a 75% improvement in eczema area and severity, versus 13.7% of patients on placebo. The statistically significant difference in EASI-75 caused the trial to meet one of its primary endpoints.
Amgen also reported significant differences in the proportion of patients scoring clear or almost clear on the subjective clinician assessment vIGA-AD and the more stringent rIGA scale. On vIGA-AD, 19.3% of the rocatinlimab cohort and 6.6% of the placebo arm met the response criteria. On rIGA, the rocatinlimab and placebo results were 16.4% and 4.9%, respectively. All the measures were taken after 24 weeks.
The potential problem for Amgen is that Regeneron and Sanofi have already racked up big numbers on EASI-75. In two phase 3 studies that supported FDA approval of Dupixent, 51% and 44% of people taking the anti-IL-4Rα antibody had (PDF) a 75% improvement in eczema area and severity. The figures for the placebo arms were 15% and 12%, respectively. Analysts compared Amgen’s data unfavorably to rivals.
“Despite meeting the ROCKET-HORIZON phase 3 study’s endpoints, the rocatinlimab results came in a bit below expectations, raising questions on how the clinical profile of rocatinlimab compares amid a growing competitive landscape in AD and on expectations for the broader ROCKET program,” William Blair analysts said in a note to investors.
Analysts asked Amgen about the positioning of rocatinlimab against Dupixent on a call to discuss the data. Murdo Gordon, executive vice president, global commercial operations at Amgen, said there are unmet needs in the atopic dermatitis market that rocatinlimab, a molecule with a different mechanism of action, may be able to address.
“We see physicians making a fair amount of switching decisions as early as three months into a patient's therapy,” Gordon said. “Even if the physician doesn't make a switching decision, we often see patients stopping therapy within 12 months. So there's a fair amount of dynamic movement of patients in this market given the limited number of mechanisms to choose from.”
Amgen included patients who had previously taken a biologic such as Dupixent in the study. However, the company declined to say what proportion of patients had prior biologic exposure when asked by an analyst. Separating out the results for biologic-experienced and naive patients could give a clearer look at how rocatinlimab compares to Dupixent and its attractiveness as a second-line biologic.
The breakdown of the prior therapies is one of several key details that Amgen is holding back for now. The Big Biotech also declined to share detailed data on the rate of fever and chills, an aspect of the safety and tolerability data that Evercore ISI analyst Umer Raffat said “was a very important thing that everyone was focused on.”
Amgen said the antibody performed as expected, and any fever and chill were mild and manageable. In an earlier phase 2b trial, 17% of patients had pyrexia—the medical term for fever—and 11% had chills. Sanofi, which is developing an antibody that targets the OX40 ligand, reported no fever or chills across doses in its phase 2b atopic dermatitis trial, although pyrexia was seen in a phase 2a study.
Amgen sees benefits to targeting OX40 rather than its ligand. Jay Bradner, M.D., executive vice president of R&D at Amgen, said an OX40 ligand muting biotherapeutic will only inhibit OX40 signaling. Engaging OX40, in contrast, will “take out the pathologic T cell” to drive T-cell rebalancing.
“With this rebalancing, we can achieve a strong and durable impact on T cell inflammatory conditions, like atopic dermatitis, but potentially by taking out the T cell compartment have beneficial effect on other downstream cytokine and pathobiologic responses. So, in a way, OX40 ligand-directed therapeutics are actually quite different than OX40-directed T cell rebalancing therapeutics,” Bradner said.
Amgen paid Kyowa Kirin $400 million upfront for rights to rocatinlimab in 2021. The biotech is running a broad development program, which includes eight pivotal atopic dermatitis trials, as it works to collect data that could turn rocatinlimab into a major product. Results from two of the other atopic dermatitis trials are due in late 2024 or early 2025.