Whenever a drug fails an Alzheimer’s clinical trial, analysts, investors and industry watchers immediately turn to look at Biogen. Will the company’s aducanumab be the one? Will it be the drug that will actually break the string of more than 150 drug failures?
Whenever a drug fails an Alzheimer’s clinical trial, analysts, investors and industry watchers immediately turn to look at Biogen. Will the company’s aducanumab be the one? Will it be the drug that will actually break the string of more than 150 drug failures?
Today, Roche announced that it was discontinuing two of its Alzheimer’s Phase III trials, CREAD I and 2, after a pre-planned interim analysis. The studies investigated crenezumab in patients with early, prodromal to mild, sporadic Alzheimer’s disease. Roche was working with AC Immune on developing the drug.
Crenezumab appeared safe, but the interim analysis showed the drug was unlikely to meet the primary endpoint of change from baseline in Clinical Dementia Rating-Sum of Boxes (CDR-SB) Score. The companies expect to present the data at an upcoming medical conference.
Roche indicated that a crenezumab trial in Colombia as part of the Alzheimer’s Prevention Initiative (API) will continue. It also says it is committed to continuing work on Alzheimer’s, including Phase III trials with gantenerumab and a Phase II anti-tau trial. The Colombia trial focuses on cognitively healthy patients who have an autosomal dominant mutation that places them at risk to develop familial Alzheimer’s disease. It is a five-year trial in collaboration with the Banner Institute funded by the National Institute on Aging.
Meanwhile, what’s going on with Biogen?
At yesterday’s 2018 fourth-quarter and year-end report, the only real mention of the drug was that in October 2018, the company had presented results at the Clinical Trials on Alzheimer’s Disease (CTAD) meeting held in Barcelona, Spain. That data was from the 36- and 48-month analyses of the long-term extension (LTE) of the Phase Ib PRIME trial of aducanumab.
Data from those analyses showed a decrease in amyloid plaque levels in a “dose- and time-dependent manner, as measured by positron emission tomography (PET). In addition, analyses of exploratory clinical endpoints, Clinical Dementia Rating Sum of Boxes (CDR-SB) and the Mini-Mental State Examination (MMSE), suggested a continued slowing of clinical decline over 36 months and 48 months.”
That appears to be positive news. The company, along with collaboration partner Eisai Co., also presented data at CTAD from their Phase II clinical trial of BAN2401, an anti-amyloid beta protofibril antibody. That study, however, did not achieve its primary outcome measure. Although the highest dose showed a statistically significant reduction in brain amyloid at 18 months, and a statistically significant slowing of clinical decline of 30 percent compared to placebo at 18 months, the primary outcome measure was designed to allow a more rapid entry into Phase III development, which it did not meet.
Almost a year ago, investors got jittery when Biogen’s chief medical officer, Al Sandrock, speaking at the Leerink Healthcare Conference, said the company had added 510 more patients to its aducanumab clinical trial. He said, “We did see more variability on the primary endpoint than assumed when we did the initial sample size estimations. So we decided to increase the sample size to maintain 90 percent power.”
This seemed to be an oblique way of saying the company wasn’t getting the results it expected, so it was increasing its sample size. It was also complicated by the fact that Biogen hadn’t seen all the unblinded data due to the trial’s structure.
At yesterday’s fourth-quarter conference call, Biogen executives chose not to comment on any chances of a look at interim data for aducanumab this year. However, data is expected from two of its Phase III trials, ENGAGE and EMERGE, later this year or sometime in 2020.
Xconomy notes, “The (multi-billion dollar) question is whether aducanumab is any different from the others to fall short, including crenezumab. Biogen has bet heavily on its fate, even announcing plans yesterday to start a third Phase III study in presymptomatic Alzheimer’s patients.”
One has to admire Biogen for its willingness to swing for the fences and go all-in on tackling some of the most difficult neurological diseases—that’s how it was so successful for multiple sclerosis and spinal muscular atrophy (SMA). Still, although Biogen is acting confident in aducanumab, many investors and analysts are skeptical. In May 2018, Wall Street analysts gave it a 50-50 chance of working.
Not much has changed since to change those odds.
