the rollout of the results at an investment conference in December, prompting a run-up that has added 41 percent to Biogen’s share price and nearly $30 billion—not a typo—to its market capitalization.
Analysts earlier this week wrote to clients that they expected good results. “With management’s bullish commentary going into the meeting, we remain optimistic in our estimates of a ‘game-changing’ effect size of BIIB037 on cognitive benefit,” wrote Leerink Partners analyst Joseph Schwartz on Monday.
Here’s what the data show:
After 26 weeks of treatment, patients receiving all four doses showed reductions in amyloid plaque that increased with the dose size. After 54 weeks, the amount of plaque reduction in the 1mg, 3mg and 10mg patients was even greater. (Data from the 6mg cohort were not yet available.) Reductions in the smallest dose group were not statistically significant.
Clearing plaque is one thing; staunching the march of dementia is another. Biogen used two standard tests, the Mini Mental State Examination and Clinical Dementia Rating Sum of Boxes, to measure cognitive decline.
Again, the effects on the patients—in this case, the score on the tests—were proportional to the step-up in dose levels.
For example, on the MMSE, the placebo group scored 3.14 points lower after one year. The 1 mg group declined by 2.21 points; the 3 mg group, .75; and the 10 mg group, only .58.
On the CDR-SB, the placebo group declined by 2.04 points over one year. The 1 mg group, 1.70; the 3 mg group, 1.33; and the 10 mg group, .59.
The differences in those scores compared to placebo will certainly be a point of discussion. Before the data were released, for example, analyst Michael Yee of RBC Capital Markets wrote that for the high dose, a 1 to 1.5 point “delta,” or difference, on the MMSE would be “very solid.” (It has come in above 2.5.)
No doubt the safety figures will spark discussion, too. Headache was a side effect in 22 percent of those taking aducanumab and five percent taking placebo. There were three deaths: two in the placebo group, and one in the 10mg group that Biogen did not consider treatment-related. (But the company did not specify the patient’s cause of death.)
The edema data were broken into two groups: Carriers of the apolipoprotein E-e4 (ApoE4) gene—which puts them at higher risk of developing Alzheimer’s—and non-carriers.
Carriers in the 1 mg and 3 mg dose groups had a five percent rate of edema; in the 6 mg group, 43 percent; and in the 10 mg group, 55 percent. Biogen said the edema caused 5 percent of the patients in the 1 mg group to stop treatment; 10 percent in the 6 mg group; and 35 percent of the 10 mg group. (No one in the 3 mg group discontinued treatment.)
Non-carriers in the 1mg group had no incidence of edema; the 3 mg group, 9 percent; the 6 mg group, 11 percent; and the 10 mg group, 17 percent. There were no discontinuations in the 1 mg and 3 mg dose groups; 11 percent of patients in the 6 mg group and 8 percent in the 10 mg group dropped out.
How those data affect Biogen’s dosing strategy is an open question, perhaps one to be answered in coming days.
Photo “My Mother’s Hands” courtesy of Ann Gordon via a Creative Commons license.
