Eli Lilly and Roche have been riding high this week on the controversial approval of Biogen’s anti-amyloid Alzheimer’s disease drug Aduhelm (aducanumab), as its new low bar could help these Big Pharmas jump the finish line.
First up is Lilly, which reached all-time highs this week as attention turned to its once highly hyped donanemab, another anti-amyloid that saw a mixed bag of data back in March, with a slight win on one disease scale undermined by a failure on a more widely used measure of Alzheimer’s.
Lilly did show much more conclusively that donanemab, which zeroes in on amyloid plaques, does reduce levels of the aggregates of misfolded proteins in the brain. This is what Biogen also showed with Aduhelm, and it turned out this week to be enough for a full FDA approval, hence the stock bump for Lilly.
The Big Pharma had, however, decided to all but shelve donanemab in the near term as it couldn’t see a regulatory path forward.
Analysts at Mizuho Americas, who spoke to Lilly’s management this week, said that may well have now changed. “Overall, it sounds like the approval raises new questions for Lilly (as it does for many of us!),” the firm said in a note to clients.
“They will now look to re-engage with the FDA to better understand the bar donanemab needs to clear to potentially obtain a more expedited regulatory approval.”
Analysts at Jefferies, meanwhile, said the FDA accelerated approval for Aduhelm, which was based on a surrogate endpoint of amyloid beta plaque reduction (and not clinical benefit) “has implications for ongoing AD studies,” most notably, it reckons, for Roche’s phase 3 GRADUATE test for its anti-amyloid-beta candidate gantenerumab, “as a much lower hurdle than demonstrating clear cognitive benefit” has now become precedent.
Jefferies, still cautious, said it remains “unclear what stance FDA may take for the field if GRADUATE fails on cognition despite significant Abeta reductions,” but says it’s probably not going to revive Roche-AC Immune’s anti-amyloid-beta candidate crenezumab, which saw its late-stage CREAD trials discontinued for futility but which is currently in an Alzheimer’s prevention study.
For Jefferies, this “has not been demonstrated to convincingly reduce Abeta plaque burden, in our view.” The firm forecasts $3 billion in global sales for gantenerumab, but at a striking 0%, “so probability so no contribution.”
Roche too has been riding high on the stock exchange this week, as investors still hope its more extensive Alzheimer’s profile could come good.
This also includes its anti-tau pipeline, with the FDA’s approval having “implications for AD programmes targeting Tau,” according to Jefferies.
Right now, midstage data for Roche-AC Immune's anti-tau antibody semorinemab in moderate Alzheimer’s are expected later this year, but it has already failed a phase 2 study in mild disease.
Roche's second anti-tau antibody UCB0107, partnered with UCB, is also slated to enter deeper testing this year. Tau had appeared to have fresh promise as a rival of sorts to amyloid. Tau theory goes that neurofibrillary tangles that form inside cells clog up the brain, and clearing this can help Alzheimer’s patients.
This hasn’t been borne out in the clinic, but after Aduhelm, maybe that doesn’t matter anymore.