Alzheimer's Study Lacks ‘Shock and Awe’ Biogen Investors Sought

(Bloomberg) -- An experimental Alzheimer’s disease drug from Biogen Inc. and Eisai Co. slowed the progression of the earliest stages of the devastating condition by 30 percent in a study, a first in the decades-long research that has been littered with failures.

But biotech investors were hoping for a bigger breakthrough.

Biogen shares dropped 8.4 percent to $351.49 as of 9:46 a.m. in New York after closing at the highest in three years in anticipation of the results Wednesday night. Eisai, which had been trading near all-time highs, plunged in Tokyo, and BioArctic AB, the Swedish company that originally developed the medicine, tumbled in Stockholm trading.

The trial itself has been shrouded in secrecy. After an initial analysis using a novel approach failed to find a significant improvement in December, Biogen and Eisai announced three weeks ago that a different approach yielded positive results, sending shares soaring.

Doctors and patient advocates said the new data presented Wednesday was promising, though more information was needed from larger, longer studies before any real promise from the drug could be accurately measured.

“It’s encouraging, but a lot more needs to be done,” said Julie Schneider, associate director of Rush Alzheimer’s Disease Center in Chicago, and one of the few outside experts who had seen the latest data released Wednesday. “I would not say it’s shock and awe.”

While Biogen’s shares had their biggest intraday drop in two years, they’re still trading about 18 percent higher than July 5’s close, before the drugmaker released the initial results for the drug, called BAN2401.
In the latest data, only the highest of five doses of the drug showed a significant benefit, slowing the progression of the disease on a novel measure called ADCOMS of 12 items compiled from more traditional approaches. It included performance on word recognition and recall, personal care, memory, problem solving and drawing.

The highest dose of the drug also had a significant benefit on a traditional test of mental function called ADAS-Cog, reducing the cognitive decline by 47 percent compared with placebo. None of the other doses of the drug were successful.

“It hints at some cognitive effect,” said Maria Carrillo, chief science officer at the Alzheimer’s Association. “We would like to see a larger, more confirmatory trial.”

Concerns on Findings

Analysts raised questions about other nuances in the findings.

Patients given the highest dose were the least likely to have a genetic predisposition to the disease, which can mean faster progression. The imbalance occurred because European regulators didn’t want them to be exposed to so much medication. In previous studies, people with the genetic mutation known as APOE4 were the most at risk for potentially harmful swelling in the brain.

As a result, patients who would have been assigned to the high dose instead were sent into a lower dose or a placebo treatment. In the study, 71 percent of placebo patients were APOE4 positive, versus 30 percent of those given the highest dose. The fact that there were fewer people predisposed to worsening faster may have been responsible for the benefit, not the potency of the treatment, some analysts said.

Eisai Falls

Eisai stock fell 10 percent Thursday in Tokyo. Company executives were undeterred by the drop in investor confidence. The company is preparing to file for conditional approval for the drug as it readies for the next phase of the study, said Masanori Tsuno, Eisai’s deputy chief clinical officer of its neurology unit, at a briefing in Tokyo.

“There are many different options for the next stage that we have been discussing,” he said. “Based on this data, the health authorities may want to consider conditional approval. We can then get applicant commitments for additional studies. There are industry examples of this happening in the U.S., Europe and Japan.”

Past Failures

The history of Alzheimer’s research has been marked by a series of high hopes and dramatic setbacks. There have been about 200 failed attempts to find a treatment -- so far in vain. The stakes are enormous for the pharmaceutical industry, as well as the millions of people grappling with the disease around the world. A successful drug to slow the progression would be a first in the space, with stratospheric sales and few rivals currently on the horizon.

Read More: Hope and setbacks little research on Alzheimer’s disease

BAN2401, which targets a protein called amyloid thought to be a cause of the disease, is in mid-stage trial, known as phase 2, and would need to go through final stages of study, or phase 3. Many of the previous failures happened in phase 2, and doctors welcomed any hint of progress in treating the disease that has become the sixth largest killer in the U.S.

“The field needs a shot in the arm right now in terms of enthusiasm because there have been so many failed phase 3 big trials,” Ronald Petersen, director of the Mayo Clinic Alzheimer’s Disease Research Center. “It certainly is encouraging that maybe this line of investigation is going to pay off when the right participants are enrolled in the study at the right phase in the disease.”

To Sharon Cohen, medical director of the Toronto Memory Program, the results were “very exciting.”

“We are seeing without any doubt a meaningful clinical slowing of disease,” she said. “We need this.”

Investors may have priced in too much hope, too soon.

“The enthusiasm built up around this data set was ridiculous,” Brian Skorney, an analyst at Baird Equity Research, said in a note Wednesday night. “It is neither the savior nor destroyer of the amyloid hypothesis. We expect a sell-off tomorrow as the irrational exuberance burns off, but would be looking for an opportunity to be buyers if it goes too far.”

--With assistance from Rebecca Spalding, Lisa Du and Dave McCombs.

To contact the reporter on this story: Michelle Fay Cortez in Minneapolis at mcortez@bloomberg.net

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

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