Results

Biogen spells out remarkable efficacy data in Alzheimer’s for aducanumab, but safety threat persists

Samantha Budd Haeberlein, Biogen

Samantha Budd Haeberlein, Biogen

Shares of Biogen jumped Thursday afternoon after an updated assessment of the remarkably positive data they’ve been collecting from the PRIME study of their Alzheimer’s drug hopeful aducanumab was leaked among investors and then quickly spread online.

Aside from the kerfuffle over how the data first began to surface, a close look at the full set of results revealed a surprisingly positive readout that will help ignite renewed enthusiasm for Biogen’s prospects in what is perhaps the toughest field in R&D — though a big safety issue remains a key concern.

Looking over the data from 196 patients, investigators reported that they tracked significant decreases in amyloid plaque burden in the brains of patients taking a titrated 10 mg dose of the drug “during 12 months of treatment in ApoE ε4-positive patients with prodromal or mild AD compared with placebo.” And they linked that to a clear and significant slowing of the disease.

Biogen’s shares ended up 1.5% at the close, after bouncing up and down as the data were passed around. In pre-market trading shares spiked 3.75%.

Investigators were able to track a slowing in the decline among patients taking a titrated dose of aducanumab. And the most common adverse effect, ARIA, “appeared” to be reduced among the titrated drug arm compared to the higher fixed dose among patients with the ApoE4 gene, which may predispose them to the disease.

The slowing in the Clinical Dementia Rating-Sum of Boxes (CDR-SB, which measures cognitive and functional performance) scale was statistically significant in the titrated arm compared to the placebo group. And the investigators say they felt the data they had gathered supported the design of their Phase III study, which puts this drug to the pivotal test.

There appeared to be a clear dose response to the drug, which is what investigators like to see.

In a release issued late Thursday, Biogen spelled out the changes in both the CDR-SB and MMSE measures, breaking out the scores by doses compared to a placebo. For the CDR-SB Group, the placebo arm worsened by an average of 1.89 points at 54 points. That was close to the 1.69 point drop for the 1 mg group, but far worse than the 0.70 in the titration arm. The 10 mg group had the best score of 0.63.

On the MMSE score, the placebo arm worsened an average of 2.45 points, but that dropped to 0.55 in the 10 mg arm and 1.00 in the titration arm.

ARIA, though, is clearly a persistent problem. The incidence of ARIA-E in ApoE4 carriers in the fixed-dose arms was 5 percent in the 1 mg/kg and 3 mg/kg arms, 43 percent in the 6 mg/kg arm and 55 percent in the 10 mg/kg arm. The incidence of ARIA-E in ApoE4 carriers in the titration arm was 35 percent.

Brian Skorney, Baird

Brian Skorney, Baird analyst

This is some of the most encouraging data the Alzheimer’s field has seen in years, leaving aducanumab as one of the top prospects now in late-stage development. While much more safety and efficacy data remain to be gathered in pivotal studies, its success at this stage marks a potential turning point, which could be richly rewarded by a market desperate for an effective therapy, especially so soon after Eli Lily’s sola flopped.

“Both abstracts highlight significant declines in plaque burden and associated benefits in terms of the rate of clinical decline, with the titration cohort showing a stat sig benefit on CDR-SB compared to placebo at 12 months,” noted Brian Skorney, who was encouraged by the extension data. He added:

 Of the 165/196 patients in the PRIME study on a fixed dose, 91 were evaluable out to 24 months. Patients switched from placebo to aducanumab did show declines in plaque burden and slower rates of cognitive/functional decline. Patients in the 10mg/kg and 6mg/kg dose groups remaining on drug saw continued benefit out to 24 months and an even more significant response than those who were switched onto drug after placebo. There were no new cases of ARIA for those continuing on aducanumab in the LTE. The one year follow up should be interpreted with caution as patients know they are on treatment and the clinical measurements are subject to high variability.

Aducanumab is a critically important drug for Biogen, which has experienced a series of pipeline ups and downs as its blockbuster Tecfidera has begun to wane on the big multiple sclerosis market.

“The data at CTAD support the positive results we have seen in our Phase 1b study of aducanumab, and they provide insight into the observed effects in patients treated for up to two years,” said Samantha Budd Haeberlein, vice president, clinical development at Biogen. “We are committed to advancing our global Phase 3 program for aducanumab as well as the scientific understanding of Alzheimer’s disease so we can help identify a treatment for the many people affected by this terrible disease.”


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