UPDATED: Pfizer, J&J Alzheimer's drug bapineuzumab flunks out in big PhIII

Pfizer ($PFE) and Johnson & Johnson ($JNJ) are reporting that in the first of four Phase III trials, bapineuzumab failed to outperform a placebo in moderating symptoms of mild-to-moderate Alzheimer's, a clinical train wreck that will only raise further doubts about the R&D track they laid down.

Investigators had gambled heavily on the belief that an IV formulation of the drug could help a group of patients who shared the ApoE4 (apolipoprotein E epsilon 4) genotype, one of four studies Pfizer and J&J's Janssen had divided between them. With the failure the companies are slamming the brakes on dosing patients in an extension study of this particular Phase III trial, though they will continue to be evaluated. The other three trials are expected to read out soon.

Pfizer didn't detail the results from the study, but a principal investigator in the trial, Reisa Sperling, told The New York Times that "there was absolutely no evidence at all of a clinical benefit of treatment on either of the primary measures..."

The focus now will shift to the non-ApoE4 group studies, where some scientists are hopeful that the drug's dismal fortunes can change for the better.

"There was no reason to believe, unless there was a miracle, that this would be positive," Harvard's Rudolph Tanzi told Bloomberg. "It will only be the results of the non-ApoE4 carriers that will inform us about the future."

The failure to register over a placebo on two co-primary endpoints--a change in cognitive and functional performance--bodes ill for one of the most closely watched late-stage programs of the year. Elan, which retained a revenue stake in their licensing pact, saw its share price plunge 19% on the news. It also is likely to cast a long shadow over Eli Lilly's ($LLY) solanezumab, which many analysts believe has an even lower likelihood of success.

"While we are disappointed in the topline results of Study 302, a more complete understanding of bapineuzumab and its potential utility in mild-to-moderate Alzheimer's disease will be gained following the availability of additional data, including data from the soon-to-be available non-carrier Study 301," said Dr. Steven J. Romano, Pfizer's senior vice president of the Medicines Development Group in the Global Primary Care Business Unit. "We recognize that Alzheimer's disease is very complex, but Pfizer, along with our partner Janssen AI, remains committed to advancing the science of Alzheimer's disease, with the ultimate goal of delivering innovative and meaningful new treatment options to patients."

Bapi and solanezumab have largely been viewed as two extraordinarily high-stakes gambles on two programs that showed an ability to reduce toxic loads of amyloid in the brains of patients diagnosed with the disease. But as these studies drew to a close, there's also been a growing sense that these drugs are aimed at a population whose disease is beyond control or amelioration. Millions of patients with the disease, and their families, have been waiting for years for some kind of treatment that can help. But so far Alzheimer's has been a disastrous field for drug developers looking to develop the next megablockbuster.

Eli Lilly has already registered a big failure in the field with the collapse of its efforts to develop semagacestat, or LY450139. And Medivation ($MDVN) took months to recover from the failure of Dimebon, which Pfizer had partnered on with a $225 million upfront. There as well, Pfizer spent a huge sum on pivotal studies. 

Analysts will be among the least surprised to see the first failure. In a number of surveys both drugs registered little better than a 1-in-5 chance of success.

- here's the press release
- get the story from The New York Times
read the Bloomberg report

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