Lundbeck is calling time (PDF) on development of Alzheimer’s candidate idalopirdine after it chalked up a clean sweep of failures in phase 3. The Danish drugmaker made the decision after learning the 5-HT6 agonist, which failed its first phase 3 in September, had come up short in its second and third late-stage studies.
Expectations for the second and third studies were dampened by the results of the earlier phase 3, in which neither dose hit the primary endpoint or showed separation from placebo. Lundbeck is holding off on releasing a full look at the data from the final two trials until scientific meetings later in the year. But the headline message is the efficacy data, when looked at alongside results from the first trial, are too weak to support a regulatory filing.
Shares in Lundbeck traded down 6% in Copenhagen after it released news of the setback as part of its fourth quarter results.
Lundbeck was developing idalopirdine, also known as Lu AE58054, with Otsuka, which paid $150 million upfront for co-development and co-commercialization rights to the program in 2013. The attention of the partners’ wide-reaching CNS collaboration now turns to Rexulti. Data from two pivotal trials of the serotonin-dopamine activity modulator in agitation associated with Alzheimer’s are due later this year.
The failure of idalopirdine leaves Axovant to fly the flag for 5-HT6 drugs. Axovant picked up its asset from GlaxoSmithKline for $5 million upfront and went on to raise $315 million in an IPO on the strength of its potential. The Lundbeck data, when paired to the fates of GSK and Pfizer’s work on 5-HT6 drugs, suggest Axovant’s IPO investors may get burnt. However, Axovant can find reasons for optimism in the design of Lundbeck’s phase 3 program.
While at first glance the Lundbeck program looks like another example of early promise failing to translate into phase 3 Alzheimer’s success, it can also be read as a misstep by the Danish company. Lundbeck tested thrice-daily 30mg doses in phase 2, only to switch to once-daily 30mg or 60mg doses in phase 3. The change was an attempt to lower the dropout rate from the 21% seen in the phase 2 treatment arm.
A PET study suggested Lundbeck could change dosing without affecting 5-HT6 receptor occupancy to the extent it reduced efficacy. Axovant and its backers are hoping that analysis and subsequent dosing decision was the undoing of idalopirdine, rather than a fundamental flaw in the 5-HT6 idea.