Roche's Alzheimer's drug fails to meet goal in long awaited trial

Roche's Alzheimer's drug candidate could not be shown to markedly slow dementia progression in two drug trials, leaving rivals Biogen and Eisai as clear leaders in a high-stakes race to launch a treatment for the memory-robbing disease.

Roche said in a statement on Monday that twin studies known as Graduate 1 and 2 had not reached their main goal of showing that the drug gantenerumab could preserve abilities such as remembering, solving problems, orientation and personal care in patients suffering from early stages of Alzheimer's disease.

The Swiss drugmaker conducted two identically designed studies, each with about 1,000 participants, who were examined and queried by physicians over more than two years. Within each study, volunteers were randomly assigned to receive either the injectable antibody drug gantenerumab or a placebo.

The drug was associated with a relative reduction in clinical decline of 8% in Graduate 1 and 6% in Graduate 2 compared with the placebo, but those results were not statistically reliable, the company said in a statement.

Credit Suisse analysts, who had seen a 20% chance of the drug reaching peak annual sales of $10 billion, described the trial failure as "unequivocal".

Roche shares were indicated down 4.8% in pre-market trading before the official 0800 GMT open.

Gantenerumab was designed to bind to aggregated forms of beta-amyloid and remove brain amyloid plaques, which are believed to play a crucial role in the slowly progressing dementia disease.

The setback will be an added challenge for CEO-designate Thomas Schinecker, Roche's head of diagnostics, who will be promoted in March. He will replace Severin Schwan, the chief executive who has led a successful campaign to diversify away from Roche's traditional focus on cancer.

The quest to develop an Alzheimer's drug, targeting beta-amyloid or other molecules, has been beset by a long list of study failures.

But rival Biogen in September scored a surprise trial success with an experimental Alzheimer's drug that it developed with Eisai, rebuilding confidence among industry executives and researchers in the beta-amyloid approach.

Biogen and Eisai said at the time their drug candidate lecanemab had slowed progression of the brain-wasting disease by 27% compared with a placebo in a large trial of patients in the early stages of Alzheimer's.

Difficult to diagnose

Most of the 55 million people suffering from dementia worldwide are likely to be affected by Alzheimer's disease, according to the World Health Organization. In 2030, dementia is expected to affect 78 million.

Alzheimer's is difficult to diagnose, especially during its early stages.

Berenberg analysts had put a 50% probability on Roche achieving 10 billion Swiss francs in peak annual gantenerumab sales. Other analysts had not included the drug candidate in their group revenue estimates, due to uncertainty.

Germany's Morphosys would have received tiered royalties of about 2% to 3% on future gantenerumab sales from its early role in developing the drug. Royalty Pharma would have been entitled to about 3% to 4% of gantenerumab sales under a 2021 deal with Morphosys.

Analysts have said the read-out from the trial would impact stock market confidence in Roche's development prowess, especially after lung cancer immunotherapy hopeful tiragolumab fell through in trials earlier this year, battering the company's shares.

Schwan earlier this year sought to curb expectations for the Graduate trials but the head of Roche's pharma unit last month acknowledged that Biogen's success with lecanemab had reignited hopes.

For now, Roche's setback leaves Biogen and Eisai as leaders in the race for a potential multi-billion Alzheimer's market. But Eli Lilly is working on another amyloid-targeting antibody drug, donanemab, with results of a key late-stage trial expected by mid-2023.

The trial success of Biogen and Eisai in September was a comeback for the pair, which became mired in controversy last year over the U.S. Food and Drug Administration's approval of Aduhelm, another beta-amyloid drug jointly developed by the two companies.

The FDA at the time based its go-ahead on Aduhelm's plaque-clearing ability rather than proof that it helped slow cognitive decline, which turned out to be a pyrrhic victory for Biogen.

The U.S. government's Medicare programme later denied broad coverage of the medicine, prompting the company to stop the commercial launch and also leading to the departure of its CEO.

Roche released only the main outcome of the trials on Monday. It plans to present detailed data at the Clinical Trials on Alzheimer's Disease conference in San Francisco on Nov. 30.