Mixed results for Alzheimer’s drugs hit Biogen

Three companies unveiled data from major trials in Alzheimer’s disease yesterday, with Biogen, Lilly and Roche all looking for a breakthrough in a therapy area littered with failures.

Of the three, Biogen’s share price was hit by underwhelmed investors, while Lilly and Roche fared better – however none of the results represented the ‘home run’ patients and clinicians wanted.

Hopes had been high for Biogen’s candidate aducanumab, which the company has fast-tracked into phase III based on promising early results. However the company presented phase Ib data at the Alzheimer’s Association International Conference (AAIC) which showed only modest effects in slowing cognitive decline in patients with mild or prodromal Alzheimer’s.

Patients on the lower doses showed little response, while those taking the higher 10mg dose showed better results, but also had worryingly high rates of amyloid-related imaging abnormalities (ARIAs) in brain scans – these included leakage of fluid from the blood in the brain. A group taking a middle dose of 6mg was added to the trial, but data didn’t show a clear correlation between dose and response, casting doubt on whether the drug was really working.

54-week data from the 6 mg/kg arm demonstrated a statistically significant reduction of beta amyloid in the brain, but failed to show a statistically significant slowing in cognitive decline.

These results aren’t a death knell for the drug as even if it can only show a modest impact on the disease, this could well be enough to represent a step forward, and allow regulators to approve it.

But the results leave Biogen with much to prove as it begins screening patients for its phase III trial, and its stock fell 4.3 per cent yesterday.

By contrast, Eli Lilly saw its share price rise 1 per cent after somewhat more encouraging data from its phase III data on solanezumab.

The drug has failed in trials aimed at treating patients with moderately advanced disease, so Lilly has switched to large studies, Expedition 1 and Expedition 2, mainly looking at mild cases of the disease.

The firm reported yesterday on Expedition-EXT, which looked at patients who had been in the placebo group and then switched to treatment on the active arm of the study.

This ‘delayed start’ group was compared to the ‘early start’ group to see if they could catch up.

The study found there was still a significant difference in cognition and function between the two groups, suggesting early diagnosis and treatment could help slow the progress of the disease.

“The data from these new analyses present exciting possibilities, and we look forward to the results of future studies in these experimental drugs,” said Maria Carrillo, chief science officer, Alzheimer’s Association. “For the delayed-start analysis in particular, if it proves to be true, it is the strongest argument to date for early Alzheimer’s diagnosis, because getting the drug earlier makes a significant difference in the outcome.”

While the data is still not hugely compelling, analysts believe it could form the basis of a future regulatory filing for the drug.

Roche’s phase III trial in early Alzheimer’s

The third major study looked at another drug, Roche’s gantenerumab, which had disappointed in earlier reported data. Its phase III SCarlet RoAD trial in people with early symptoms of Alzheimer’s was stopped based on preliminary results suggesting successful completion was very low. However the research programme has continued to pinpoint whether the drug has a measurable effect on amyloid and tau, two key biomarkers for the disease.

Phase III trials in people with very early signs of Alzheimer’s showed a monthly injection of gantenerumab modestly reduced levels of amyloid in the brain on PET scans, as well as levels of tau in spinal fluid.

Philip Scheltens, director of the Alzheimer’s Centre at the VU University Medical Centre in Amsterdam, and a principal investigator of the study, said the results suggested the gantenerumab dose in the phase III Scarlet RoAD trial was probably too low. Roche is likely to consider higher doses of the drug for future trials.

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