Bapi Fails – New Alzheimer Drug Disappoints in Trials

Bapi Fails – New Alzheimer Drug Disappoints in Trials

August 8th, 2012 // 2:33 pm @ jmpickett

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Two weeks after results of a closely watched Alzheimer’s failed to meet two primary endpoints, a related study has similarly disappointed. The topline results from a study in patients with mild-to-moderate Alzheimer’s disease who do not carry the ApoE4 genotype failed to meet the co-primary clinical endpoints – a change in cognitive and functional performance compared to placebo. The earlier study involved patients who do carry the ApoE4 genotype (back story).

Based on the combined results, Pfizer and Johnson & Johnson, which have been running the trials along with Elan, have decided to discontinue most all* other studies for the Alzheimer’s treatment called bapineuzumab in patients with mild-to-moderate disease. This pertains to all Phase III studies that have been under way, although follow-up evaluations and final data analyses will be conducted.

“The ‘bapi’ program is “shut down” and the company has “no plans” to file for approval,” says ISI Group analyst Mark Schoenebaum in an investor note. “The company has analyzed subgroups and found no signal that they believe could lead to a commercial future for the drug at this time. All trials using the IV formulation are being shut down.” He noted the consensus Wall Street estimate for bapi sales had been about $1 billion annually if the trials had succeeded.

“We are obviously very disappointed in the outcomes of this trial. We are also saddened by the lost opportunity to provide a meaningful advance for patients afflicted with mild-to-moderate Alzheimer’s disease and their caregivers,” says Steven Romano, a senior vp and head of the medicines development group in the global primary care business unit at Pfizer, in a statement.

However, bapi may continue in some fashion. “What is not said explicitly but is implied in the press release (and confirmed by Pfizer per our conversations with them) is that an ongoing Phase 2 study will continue looking at the subcutaneous (SQ) formulation of bapineuzumab,” writes Sanford Bernstein analyst Tim Anderson in an investor note. “We are not clear how to interpret this, but one possibility is that Pfizer and its partners will eventually take the SQ formulation into a Phase 3 pre-Alzheimer’s population, contingent on the companies seeing positive biomarker data in Phase 2 (this is the primary endpoint in the Phase 2 trial).”

Wall Street was not surprised, though. Three years ago, the drug failed to achieve statistical significance and also raised the risk of a potentially serious side effect, especially in people with a genetic risk of developing Alzheimer’s. Twelve people developed a build-up of fluid in the brain called vasogenic edema. And 10 of those cases were in people who have the ApoE4 gene, which significantly raises their risk of developing Alzheimer’s (back story).

The results also have implications for Eli Lilly, which is developing a similar drug, although investors are not betting against success, given that Alzheimer’s has proven to be a persistently difficult ailment to combat. A recent survey of 146 institutional investors gave, on average, 21 percent probability that bapineuzumab will hit all primary endpoints. Similarly, just 14 percent gave solanezumab, which is being developed by Lilly, a chance of meeting its study goals (see this).

A failure for Lilly, by the way, may add still more pressure on the board and ceo John Lechleither to alter their long-held strategy of avoiding a large deal with another big drugmaker. Lechlieter has been adamant that such combinations generally do not yield forecast savings and benefits, but he has repeatedly conceded in recent years that the Alzheimer’s drugs are a huge bet.