That didn't go as planned for Biogen Inc. (BIIB) .

Shares of the biotech giant plummeted $45.83, or about 12%, to $338 in late-afternoon trading Thursday after mid-stage trial results of its Alzheimer's drug left analysts and investors questioning the efficacy of the treatment when compared to certain measures.

BAN2401, which is being developed with Eisai Co. Ltd. (ESALY) , was shown to reduce the rate of cognitive decline in patients with the neurodegenerative disease by 30% at the highest dose compared to placebo over an 18-month period, which exceeded analysts' expectations of a 15-20% reduction.

The drug showed statistically significant improvement across a few composite measures, including the Alzheimer's Disease Assessment Scale-cognitive subscale, showing a 47% reduction in cognitive decline. BAN2401 also reduced the amount of amyloid plaque buildup by 93%.

Yet, the Alzheimer's antibody failed to produce any meaningful difference compared to one common measure. When measured against the Clinical Dementia Rating Sum of Boxes scale, BAN2401 only performed 26% better than the placebo, which was not a statistically significant difference. CDR is a more meaningful tool to measure cognitive ability rather than the ADCOMS measure that showed the 30% reduction because CDR is FDA-approved and can be interpreted better, said Yatin Suneja, an analyst for SunTrust Robinson Humphrey.

Matt Phipps, an analyst with William Blair, doesn't think ADCOMS should be discredited right away because it does take components from other established, proven methods, he said.

Another concern about the data stems from the lack of patients from the treatment group with the highest dose who have a genetic carrier associated with Alzheimer's called ApoE4 compared with the placebo group, which could have influenced what investors saw from an efficacy standpoint, Phipps said.

"You're not doing an apples-to-apples comparison," Suneja said. 

Cognitive decline was only significantly reduced in the highest dose, and the second-highest dose followed the same trend, but other doses were either in-line or below the placebo, which does not build much confidence about the drug, Phipps said.

"All other doses didn't show much of anything," Phipps said. "They're not expected to be significant necessarily, but you should still see a little bit of a difference."

Despite the worries over some aspects of the results, Biogen and Eisai think the data supports continued research into the amyloid hypothesis of targeting amyloid plaque buildup in the brain as a root cause of Alzheimer's, and Biogen was encouraged by what the results mean for aducanumab, the company's other amyloid-targeting drug, which just wrapped up enrollment for its Phase III tests.

"These data, as well as the data from the Phase 1b study of aducanumab, have thus further deepened our conviction in targeting Aβ as one of the fundamental causes of Alzheimer's disease," Al Sandrock, chief medical officer for Biogen said in an email.

Suneja wrote that aducanumab had already shown statistically significant improvement of cognitive ability on the CDR scale, so he remains "cautiously optimistic" about the program moving forward.

Data from late-stage trials of aducanumab are expected to come in as early as 2020.

Suneja reiterated his buy recommendation on the stock and kept his price target at $392. Phipps also maintained his buy rating. Analysts have a consensus "buy" rating with 14 buys and 7 holds on Biogen.

Biogen soared by more than 20% in early July after it announced the initial results from Phase II trials were promising, and the stock is up 7.8% over the year to date.

Suneja thinks the price jump was a knee-jerk reaction based off the limited amount of information was available at the time and that it should taper out to a price more in-line with the results, he said.

Shares were trading close to the company's 52-week high before the company released the test results Wednesday.

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