It’s Make or Break Time for Biogen’s Alzheimer’s Drug

(Bloomberg) -- Biogen Inc. stunned Alzheimer's researchers in March when it said its highly awaited Alzheimer's treatment aducanumab was unlikely to work. Seven months later, the company reversed course and said the drug did work after all -- at least in one of two large trials.

On Thursday, Biogen scientists will present detailed results from those trials for the first time in a special hour-long session at a meeting of Alzheimer's specialists in San Diego. Much is riding on the presentation, both for the pharmaceutical industry and for the millions of Alzheimer's patients and their families grappling with the incurable disease.

“It is hugely important,” said Murali Doraiswamy, director of the neurocognitive disorders program at the Duke University School of Medicine. “It is coming at a critical time for the field.”

For decades, scientists have feverishly debated the cause of Alzheimer's disease. Many drug companies have pursued one potential culprit, clumps of protein called amyloid that clog the brains of Alzheimer's disease patients. And for years, drug after drug has failed. Overall, there have been about 200 failed attempts to find a treatment.

If Biogen's data holds up, it could help pave the way for the U.S. Food and Drug Administration to approve the first-ever drug that slows the course of the debilitating disease. And it could lead to a revival for other amyloid-based drugs, by encouraging companies with similar products to keep testing and investors to keep pouring money into the field.

But if the aducanumab presentation is greeted skeptically at the meeting, it could be a sign that Biogen will face a tough reception at the FDA, and that researchers will need to spend more effort pursuing drugs that target other possible causes of Alzheimer's.

Biogen shares have fluctuated wildly in 2019, with a one-day plunge of 29% and a 26% rally on another day. They are down about 4% for the year, trailing the 14.7% gain in the Standard & Poor's 500 Health Care Index.

The company said it plans to submit the drug for approval in early 2020. Biogen declined to make its executives available for interviews prior to the presentation in San Diego.

‘Death Throes'

Before the company's about-face in October, the amyloid hypothesis was “in its death throes,” Doraiswamy said. For drug companies testing anti-amyloid drugs, a positive result “would be almost like manna from heaven,” he said.

“It is going to be quite a show,” said Zaven Khachaturian, editor-in-chief of the medical journal Alzheimer's & Dementia. “People who support the amyloid hypothesis feel like this would be vindication, so there is great anticipation.”

Amyloid skeptics also are watching the data carefully to see if the details truly support Biogen's interpretation. Even amyloid proponents say they're reserving judgment.

“A lot of people like me are largely on the fence about it,” said John Hardy, a geneticist at University College London who in 1991 was among the first to hypothesize that amyloid caused the disease. “We are interested and excited, but we don't think this trial is a done deal yet. We are waiting for the evidence.”

Read more: How Biogen salvaged its Alzheimer's drug after a costly failure

Interpreting the trial results is complicated because Biogen will be presenting data on two incomplete studies. They are unfinished because the drugmaker stopped the tests early in March, saying they were unlikely to show positive results, only to change its mind in October after it had looked at the data in more detail. That makes the results more complicated to interpret.

When the company's researchers analyzed the full results last summer and early fall, which included three months more of treatment data than were available when the studies were halted, one trial turned out to be clearly positive, at least at the higher of two doses, Biogen said in October. The second trial still failed to show an effect. But Biogen now believes that may be because there wasn't a sufficient number of patients who got sustained treatment at the highest dose.

At the conference, 1,600 doctors and brain scientists will be looking for more details on safety and whether the numerous efficacy measures in the trials show generally consistent results, even when the differences weren't statistically significant. They also want to hear a more convincing explanation from Biogen of why the results of two very similar trials were so divergent.

Analysts will be parsing the data carefully to see if there were any unexpected statistical imbalances between patients who were on placebo and those who got the higher, purportedly effective doses.

“I am really at 50-50” as to whether the FDA approves it, said Jeffrey Cummings, a neurologist at the University of Nevada, Las Vegas.

Shares Whipsawed

Given the data ambiguities, the agency could decide the trials are insufficient and demand an additional study to clarify the results. But Cummings said he expected “a lot of public pressure” to approve the drug. That could sway the FDA to give Biogen a conditional approval, contingent on performing more studies to confirm aducanumab's benefits.

Wall Street analysts are split on what to think about the drug's prospects.

On Dec. 2, shortly after lowering Biogen to underperform, Brian Skorney, an analyst at Robert W. Baird & Co., put out a top 10 list of reasons the drug won't be approved, including an “unreliable” statistical analysis and a “ridiculously small” clinical benefit.

Bulls, including SVB Leerink analyst Geoffrey Porges, see it differently. “The probability of approval is high,” Porges said in a note to clients on Nov. 11, calling the results of the first trial “the first unequivocally positive pivotal trial in this disease.” He rates the stock outperform.

Hardy, the geneticist, said that almost 30 years ago, when he dashed off an editorial in a medical journal proposing that amyloid was a main trigger of Alzheimer's disease, he had no idea it would lead to decades of polarized debate over the disease's origins.

If the Biogen data does hold up and the drug is approved, the effects will likely be modest and, given its limitations, the drug wouldn't necessarily be used by millions, he said. But it would prove that anti-amyloid drugs could work and pave the way for other, much more effective ones in the future.

“I think of its importance being more like the Wright brothers on that beach in North Carolina,” Hardy said. “They showed you can fly.”

To contact the reporter on this story: Robert Langreth in New York at rlangreth@bloomberg.net

To contact the editors responsible for this story: Drew Armstrong at darmstrong17@bloomberg.net, Mark Schoifet, Timothy Annett

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