Biogen isn’t due to report results from its phase 3 trials of Alzheimer’s disease antibody aducanumab until 2020 at the earliest, but its unwillingness to give any hint about interim data is spooking investors.
The biotech stuck to its policy of not providing any comments on the topic on its fourth-quarter results call, despite questions about a possible futility analysis which analysts at William Blair think could be due right about now, assuming their estimate that Biogen hit the 50% enrollment mark in its studies in mid-2017 is accurate.
Biogen’s call took place just before Roche and AC Immune announced they were stopping trials of rival Alzheimer's antibody crenezumab after their own futility analysis indicated little chance of a positive outcome, and that outcome weighed on Biogen’s shares after hours.
Analysts are desperate for information on how the aducanumab trials are progressing, with Jefferies pointing out in a research note that “stock would be easier to own if [Biogen] ends up disclosing more info … no info makes it too uncertain for some fund managers.”
“If we get to mid-19 and we hear nothing—it likely passed w/o stopping (neutral event) either way and they're close to final data,” they suggest.
Biogen did say that it was starting a third phase 3 study of aducanumab along with partner Eisai to see whether early use of the antibody can prevent or delay the clinical onset of Alzheimer's, but that left some wondering whether that was a sign of optimism about the prospects for the drug or pessimism about the current studies’ chances of hitting the mark.
Biogen’s chief medical officer Al Sandrock M.D., Ph.D., said on the call that the new trial was prompted in part by new FDA guidance (PDF) on routes to approval for early Alzheimer's drugs, telling investors: “We believe one day, the standard of care will be to treat with amyloid lowering drugs as early as possible and this trial will go a long way toward informing that.”
Jefferies say they don’t see any read-through from the decision, as Biogen “always wanted to go earlier in disease.” They add: “In the long term, we believe its phase 3 Alzheimer’s program (data not until early 2020 at the earliest) should work.”
Biogen is keen to point out the differences between aducanumab and Roche’s drug. Aducanumab (and Biogen’s earlier-stage Alzheimer's candidate BAN2401) is highly selective for soluble amyloid beta oligomers as well as insoluble fibrils, according to Sandrock.
He also said on the call that crenezumab’s IgG4 backbone means it “doesn't have full effect or function” against amyloid—unlike aducanumab and BAN2401 which are based on IgG1—and suggested crenezumab’s phase 2 data did not show any significant lowering of amyloid plaque.
William Blair also reckon there are “fundamental differences between crenezumab and aducanumab that make any read-through very limited, if at all.”
They note that crenezumab’s IgG4 structure was an attempt to reduce the side effect known as ARIA (amyloid related imaging abnormalities), but while this is undesirable “it may be a surrogate marker of beta-amyloid plaque removal in the brain, and lacking IgG1 Fc interactions may prevent crenezumab from properly activating the immune system to remove the plaques.”
The biotech was down 3% in pre-market trading.