Lundbeck has stopped development of a subcutaneous formulation of its migraine drug Lu AG09222 as the Danish drugmaker switches its focus to intravenous delivery after seeing phase 2b data, delaying the completion of the trial in the process.
The company started the trial last year to determine the best route of administration for Lu AG09222, an anti-PACAP antibody. Rival programs from Amgen and Eli Lilly have already hit the rocks, with the former reporting no benefit over placebo and the latter stopping after phase 2. But the success of an intravenous version of Lu AG09222 in migraine prevention led Lundbeck to assess whether subcutaneous delivery is viable.
A prespecified interim futility analysis of the subcutaneous data has, however, led Lundbeck to stick with the IV delivery route. Lundbeck, which performed the analysis after enrolling 75% of the targeted patients, built the interim review into the study to check whether it needed to add an optional intravenous cohort.
Leerink Partners analysts said in a note to investors that Lundbeck determined subcutaneous delivery “was not demonstrating the desired treatment effect.” The analysts have questions about the implications for the IV formulation.
“The initial news is disappointing that the sub-q formulation is sub-optimal, and that the company is moving to an IV-based formulation,” the analysts said. “There has been investor skepticism regarding this mechanism given that both Lilly and Amgen abandoned their PACAP programs, and what we don’t know from this news is whether the mechanism or the formulation is the problem.”
The analysts will need to wait longer than expected for answers, with Lundbeck now aiming to complete the study in the first half of next year. Lundbeck will use the time to enroll and dose patients in the new intravenous cohort. If everything goes to plan, the company will move into phase 3 in the second half of next year.
Johan Luthman, executive vice president and head of R&D at Lundbeck, discussed (PDF) the interim analysis on an earnings call back in February. The best-case scenario would give Lundbeck “full optionality with the different modes of administration,” Luthman said. Noting data may limit Lundbeck to one route of delivery, Luthman added that Lundbeck’s existing intravenous migraine prevention drug is “doing extremely well.”
Leerink analysts said it “may be the case” that Lundbeck can leverage the Vyepti clinical infusion infrastructure for Lu AG09222. However, the analysts said they “still believe that the larger opportunity is subq dosing and that opportunity appears to be truncated somewhat.”