Lundbeck has chalked up another Phase III failure for the Alzheimer's field. The Danish drugmaker has yet to share a detailed look at the data, but the top-line results indicate a total washout, with neither dose hitting the primary endpoint or showing separation from placebo.
For the Phase III trial, Lundbeck and its collaborator Otsuka randomized more than 900 patients with mild-to-moderate Alzheimer's to receive either a placebo or one of two doses of its 5-HT6 receptor antagonist, Lu AE58054, on top of 10 mg of donepezil. Both the 30-mg and 60-mg doses of Lu AE58054 failed to improve cognition on the Alzheimer's Disease Assessment Scale-cognitive subscale. And, in a major blow to the drug’s chances, the trial was unable to detect separation from placebo.
Lundbeck is due to deliver data from two more Phase III trials of Lu AE58054 in the first quarter of next year, which, in theory, could provide evidence to support its belief that hitting 5-HT6 improves cognition. But, with the top-line data devoid of reasons for optimism, investors were quick to fear the worst. Lundbeck, which has a market cap north of $6 billion, saw its stock trade down 15% in early trading in Denmark.
The data dragged down Axovant Sciences ($AXON), too. Axovant became the posterchild for 5-HT6 in 2015 when it picked up a discarded GlaxoSmithKline ($GSK) Alzheimer's program for $5 million and parlayed it up into a $315 million IPO. With the Lundbeck data casting doubts on the viability of the 5-HT6-targeted approach to Alzheimer’s, shares in Axovant fell by more than 20% before rallying to close down 12%.
For Axovant and its investors, the hope now is that the late-stage fail, rather than sounding the death knell for 5-HT6 receptor antagonists, is evidence Lundbeck botched the transition from Phase II to III. Notably, Lundbeck went from thrice-daily 30-mg doses in the Phase II, to once-daily 30-mg or 60-mg doses in the Phase III. Lundbeck changed the dosing regimen in response to the 21% dropout rate in the Phase II treatment arm.
The Danish drugmaker tried to foresee whether the changes to the regimens would affect efficacy by running a PET study. That study looked at the rates of 5-HT6 receptor occupancy achieved by once-daily 30-mg and 60-mg doses of Lu AE58054, resulting in data Lundbeck felt supported the use of the revised regimens. Now, with one Phase III fail in hand and neither of the ongoing studies using a dose above 60 mg once a day, the merits of that decision have been called into question.