Lebrikizumab

Amgen paid Kyowa Kirin $400 million upfront for rights to rocatinlimab in 2021.\n Amgen’s $400 million eczema drug candidate has recorded two more phase 3 victories. The data drops provide more evidence that the Kyowa Kirin-partnered rocatinlimab improves outcomes in atopic dermatitis, but questions about the positioning of the anti-OX40 antibody versus Sanofi and Regeneron’s Dupixent remain unanswered.Last year, Amgen and Kyowa shared the first data from its broad phase 3 rocatinlimab program. The study met its primary endpoint, but analysts compared the results unfavorably to the data on Dupixent. Adjusted for placebo, 19.1% of people on rocatinlimab had 75% improvement in eczema area and severity after 24 weeks of treatment. The comparable figures from Dupixent trials are as high as 36% after 16 weeks.Amgen sees an opportunity for a drug with a different mechanism of action, citing evidence about how often patients stop or switch therapies. Saturday, the Big Biotech and Kyowa presented results to make the case that rocatinlimab can seize that opportunity.The latest data come from Ignite and Shuttle, two trials from Amgen and Kyowa’s broader Rocket program. Ignite randomized 769 adults with moderate to severe eczema, including an undisclosed number of patients previously treated with a biologic or systemic JAK inhibitor, to receive one of two doses of rocatinlimab or placebo. The high dose was identical to the only dose used in the earlier phase 3 trial. On the high dose, 42.3% of patients met the 75% improvement criteria, EASI-75. The placebo-adjusted EASI-75 was 29.5%. The lower dose was less effective, but the result was still numerically higher than in the earlier phase 3, with a placebo-adjusted difference of 23.4%. Jefferies analysts said in a note to investors that the results are “optically more compelling” than the earlier data.The other study, Shuttle, randomized 746 adults with moderate to severe eczema to receive one of two doses of rocatinlimab or placebo. Again, the high dose was the same dose used in the earlier phase 3 trial. Participants in Shuttle also received topical corticosteroids and/or topical calcineurin inhibitors. The placebo-adjusted EASI-75 results were 28.7% and 30.4%, respectively, on the low and high doses.Amgen, which paid Kyowa $400 million upfront for rights to rocatinlimab in 2021, also reported wins on two versions of an investigator eczema assessment scale in Ignite and Shuttle. Safety was generally consistent with the profile seen in earlier studies, according to Amgen and Kyowa.“In totality, the rocatinlimab results validate the OX40 mechanism, likely supporting a moderate commercial opportunity for patients after Dupixent/Ebglyss,” William Blair analysts said in a March 10 note.However, the readouts “still leave potential room for improvement with future OX40/OX40L targeting therapies,” added the analysts, pointing to Inmagene\'s OX40-targeting monoclonal antibody IMG-007.Three more readouts are coming up. Amgen and Kyowa are aiming to publish phase 3 results from Ascend, a trial that is assessing dosing beyond 24 weeks, and the adolescent Astro study in the second half of the year. A second trial in adolescent patients, Orbit, is underway, as are phase 2 and 3 trials in asthma and prurigo nodularis. The studies are testing the idea that rocatinlimab rebalances the T-cell compartment.

iStock, Natalya Kosarevich In September 2024, a readout from a separate trial of rocatinlimab elicited mixed reactions from analysts, who found the antibody’s efficacy in that study to be underwhelming. Amgen and Kyowa Kirin’s anti-OX40 antibody rocatinlimab vindicated itself this weekend, with new Phase III data pointing to its strong efficacy in moderate to severe atopic dermatitis. These findings come from the ROCKET-IGNITE study, one of eight trials under the partners’ late-stage ROCKET clinical development program for rocatinlimab. Results showed that 42.3% of patients given 300-mg rocatinlimab once every four weeks saw at least a 75% reduction from baseline in Eczema Area and Severity Index scores (EASI-75) at 24 weeks. This treatment effect represented a significant 29.5% difference versus placebo, according to Amgen’s news release. At this dose level, 23.6% of patients achieved clear or almost-clear skin at 24 weeks, representing a 14.9% advantage over placebo. Amgen and Kyowa Kirin presented these data Saturday at the 2024 annual meeting of the American Academy of Dermatology Analysts at Leerink Partners called these findings “surprisingly positive” in an investor note on Sunday, pointing to a prior readout from ROCKET-HORIZON . Released in September 2024, data from the HORIZON trial found that 32.8% of rocatinlimab-treated patients achieved EASI-75, representing a 19.1% difference from placebo. While Amgen at the time declared victory in HORIZON, calling rocatinlimab’s effect a “ statistically significant improvement ” in disease severity, analysts were unconvinced. Jefferies called the magnitude of effect “modest,” while BMO Capital Markets said the data “appear to fall short of agents like Ebglyss/Dupixent.” Leerink, in its note on Sunday, said it found HORIZON’s results to be “underwhelming.” Meanwhile, IGNITE’s outcomes were “more compelling,” according to the Leerink analysts, despite testing a similar dose as HORIZON. Still, the analysts flagged instances of pyrexia (fever) and chills—which they called an “adverse event of interest”—that occurred more frequently in rocatinlimab-treated patients. Amgen explained these side effects as “mainly a first dose effect and therefore not commonly seen on subsequent doses,” as per the Leerink note. Amgen and Kyowa Kirin on Saturday also released data from two other ROCKET studies. The first, dubbed SHUTTLE, showed that rocatinlimab can elicit significant rates of EASI-75 when combined with topical corticosteroids or topical calcineurin inhibitors. The second, named VOYAGER, found that rocatinlimab does not interfere with response to tetanus and meningococcal vaccines. Correction (March 11): This story has been updated from its original version to clarify that Amgen is partnered with Kyowa Kirin on rocatinlimab. BioSpace regrets the oversight.