August 28, 2017
By Mark Terry, BioSpace.com Breaking News Staff
Cambridge, Mass.-based Biogen has a little bit of a problem. Investors and just about anyone else interested in a possible treatment for Alzheimer’s disease is waiting to hear about its clinical trials for aducanumab. The problem is that there won’t be a final readout until 2019 or 2020, which is a long time to wait. Today the company released a tiny bit more data from its Phase Ib trial extension, and it’s unlikely to satisfy anyone.
The new data looked at the 143 patients who remained in the long-term extension (LTE) of its ongoing Phase Ib study. It included data from the placebo-controlled period and LTE for patients treated with aducanumab up to 24 months in the titration group and up to 36 months in the fixed-dose groups. The company indicated, “The results are consistent with previously reported analyses from this ongoing Phase Ib study and support the design of the ongoing Phase III studies of aducanumab for early Alzheimer’s disease.”
Which is good, as far as it goes. The Phase 1b trial is a randomized, double-blind, placebo-controlled, multiple-dose study to evaluate the drug’s safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and clinical effects of the drug in patients with prodromal or mild Alzheimer’s.
The most commonly reported side effects were headache, fall and amyloid-related imaging abnormalities (ARIA). Of the 185 patients receiving the drug in the Phase Ib trial, 46 patients experienced ARIA-E (edema). There were no new cases of edema in patients who continued with the same dose, and the incidence of edema in patients that moved from placebo to aducanumab was consistent with the incidence in the placebo-controlled arm. Six patients had more than one episode of edema.
On a more definitive note, the company stated, “In patients treated up to 24 months in the titration cohort, amyloid plaque reduction as measured by positron emission tomography (PET) was consistent with the dose- and time-dependent results observed in the fixed-dose cohorts. Analyses of exploratory clinical endpoints, Clinical Dementia Rating sum of boxes (CDR-SB) and the Mini-Mental State Examination (MMSE), were consistent with the results from the fixed-dose cohorts and suggested a continued benefit on the rate of clinical decline during the second year of treatment.”
In addition, patients receiving the drug up to 36 months also showed a decrease in amyloid plaques.
All good and all supporting the company’s drug design and what is known to-date about aducanumab. What it doesn’t really indicate, and it’s likely the big question, is whether the drug improves cognition in Alzheimer’s patients enough to make it worthwhile. It’s not just a big question for Biogen, but a huge question for all Alzheimer’s researchers.
The predominant theory in Alzheimer’s disease drug research focuses on the elimination of amyloid-beta, which builds up in large quantities in the brains of Alzheimer’s patients. So the theory is that if you clear the amyloid-beta or prevent it from accumulating you can treat Alzheimer’s disease.
Today’s release supports that aducanumab clears amyloid-beta. Other drugs have as well. What they haven’t necessarily shown, and today’s release only suggests, is whether the patient’s memory or cognition improves after treatment. This problem throws a lot of doubt on the amyloid hypothesis, and perhaps only time will tell.
David Liang, writing for The Motley Fool in April, wrote, “Unfortunately, however, aducanumab is only the latest in a long line of potential AD products which have shown this effect. Back in 2012, Pfizer (PFE) and Johnson & Johnson (JNJ)’s bepineuzumab showed a similar ability to clear amyloid plaques from the brain. However, in late-stage trials, while bepineuzumab did continue to clear this plaque, the drug did not demonstrate the ability to slow or halt the underlying progression of AD. Similarly, Eli Lilly’s solanezumab, which also showed promising ability to destroy amyloid, failed in 2016 to demonstrate disease-slowing effects for AD in late-stage clinical trials.”
Time will tell if Biogen is on the right track, or if the drug is more effective as a preventative than as a treatment, given the early-stages of the disease the trial focuses on. It may also underline that not enough is understood about the disease yet to develop an effective treatment.
