Pfizer said that bapineuzumab failed to show efficacy in one study population—Alzheimer's patients who carry the Apo-E4 genetic marker, effectively knocking out 50% of its potential market. But the odds of the drug working in non-carriers are slightly higher, analysts say, offering a ray of hope that Pfizer and its partners could still grab a piece of this potentially multibillion-dollar category.
Pfizer's top-line, or non-quantified, statement about the Phase III trial results offered the public its latest glimpse at bapineuzumab, a closely watched Alzheimer's compound being co-developed by Pfizer, Johnson & Johnson and Elan. Expectations for the drug were already low, so Wall Street isn't taking the news as a letdown in the classic sense.
“These initial results will naturally make investors more skeptical than they already are,” wrote the Sanford Bernstein analyst Tim Anderson in a research note.
The antibody, which targets the beta-amyloid protein believed to play a central role in the pathology of Alzheimer's disease, failed to meet a co-primary endpoint in patients who carry the Apo-E4 allele, according the statement. The Alzheimer's population is split roughly 50-50 among those who carry this genetic marker and those who don't. Carriers have increased beta-amyloid plaques in their brains, a higher risk of getting the disease, and more rapidly progressive disease.
While Phase III data among non-carriers have yet to be top-lined, in Phase II trials the drug came closer to showing clinical efficacy in this population than among carriers. That means that non-carriers may show a somewhat higher probability of success, several analysts said.
As to why that is, too much buildup of plaque may make it difficult for drugs to work effectively. Since non-carriers don't have the defective Apo-E4 allele, “Bapi could work more effectively in them,” argued ISI Group's Mark Schoenebaum in a webinar this morning. How likely it is that the drug works in the non-carrier trial is harder to predict.
Schoenebaum estimated the worldwide cholinisterase inhibitor market (i.e., Alzheimer's market) at $6 billion. Even if the drug were to work safely in half the disease population, a sizable payoff awaits. He models a 25% probability of success and about $1 billion in bapineuzumab peak risk-adjusted revenue, in-line with consensus.
Pfizer says a non-carrier US trial will be top-lined later this summer. The companies are running two more trials in Europe, one among carriers and one among non-carriers, and plan to discuss those in more detail by early September, likely after top-lining the remaining US trial.
Even assuming higher odds of success in non-carriers, the “overall outlook [is] fading,” wrote Barclay's Tony Butler, adding that he thinks the study population was probably too advanced in their disease to gain a therapeutic effect. Pfizer is expediting the futility interim analysis for the international studies and is discontinuing the carrier arm of an extension trial—disclosures that “seem negative to us as PFE may be moving in a less optimistic direction.”
The results also put more pressure on Eli Lilly and its late-stage antibody solanezumab, which also attacks beta-amyloid plaque. “We had held a higher probability of success for bapineuzumab than LLY's solanezumab,” noted Butler.
Lilly is not running separate trials of carriers and non-carriers for solanezumab. The two existing trials mix both cohorts. But it plans a separate analysis that will look at biomarkers, Schoenebaum said.