- Studies show little benefit, but without statistical significance
- Roche’s setback leaves Biogen and Eisai as market leaders in this field
- Commitment by the designated Roche CEO to revive development skills
- Roche shares down 3.4%, development partner Morphosys down 29%
Nov 14 (Reuters) – Roche’s Alzheimer’s drug candidate (ROG.S) has failed to be shown in two drug trials to slow the progression of dementia, leaving rivals Biogen (BIIB.O) and Eisai (4523.T ) are leading a high-stakes comparison racing to bring a treatment to market for the memory-wasting disease.
Roche said in a statement on Monday that the twin studies, known as Graduate 1 and 2, had failed in their primary goal, which was to show that the drug gantenerumab could preserve skills like memory, problem-solving, orientation and personal hygiene in patients with early-stage Alzheimer’s disease.
The Swiss drug manufacturer carried out two identically designed studies, each with around 1,000 participants, who were examined and interviewed by doctors over a period of more than two years. Within each study, volunteers were randomized 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 to placebo, but these results were not statistically significant, the company said in a statement.
Credit Suisse analysts, who saw a 20 percent chance that the drug would reach peak annual sales of $10 billion, called the study’s failure “clear”.
Berenberg analysts had given a 50 percent chance of gantenerumab reaching the $10 billion peak.
Roche shares fell 3.4% to their lowest level in almost seven weeks.
Shares in US drugmakers Biogen Inc (BIIB.O) and Eli Lilly and Co (LLY.N), which are developing competing treatments for Alzheimer’s, rose 3.8% and 2.3%, respectively, in premarket trading.
Analysts said the study’s findings would hurt stock markets’ confidence in Roche’s research prowess, particularly after hopeful lung cancer immunotherapy drug tiragolumab failed trials earlier this year, hurting the company’s shares.
“The development pipeline has disappointed a bit too often to keep the stock on a favorites list,” analysts at Luzerner Kantonalbank said in a research note.
Gantenerumab was designed to attach to aggregated forms of amyloid beta and clear amyloid plaques in the brain, which are thought to play a crucial role in slowly progressive dementia.
The setback will be an additional challenge for CEO-designate Thomas Schinecker, Roche’s head of diagnostics, who will be promoted in March. He replaces Severin Schwan, the Chief Executive Officer, who has led a successful campaign to diversify away from Roche’s traditional focus on cancer.
The quest to develop an Alzheimer’s drug that targets beta-amyloid or other molecules has been plagued by a long list of study failures.
But Biogen achieved surprising trial success in September with an experimental Alzheimer’s drug it developed with Eisai, boosting confidence among industry leaders and researchers in the beta-amyloid approach.
Biogen and Eisai said at the time their drug candidate lecanemab slowed the progression of the brain-wasting disease by 27% compared to a placebo in a large study of patients in the early stages of Alzheimer’s disease.
The failure of Roche’s study “removes the major competitive risk for lecanemab,” Baird analyst Brian Skorney said in a note.
The Swiss company’s compound primarily targeted larger amyloid structures, while Biogen’s lecanemab targeted earlier stages of amyloid assembly, among other differences in the molecules and study designs.
Roche only published the main results of the studies on Monday. Detailed data is scheduled to be presented at the Clinical Trials on Alzheimer’s Disease conference on November 30 in San Francisco.
Rachelle Doody, Roche’s head of neurodegeneration, said she was very disappointed, adding that testing to remove amyloid was also less than hoped.
“We will show that there is an association between amyloid reduction and clinical outcomes. It’s just that if you don’t get the amyloid reduction you expect, you won’t get the clinical outcomes you expect,” she told Reuters.
The global Alzheimer’s Association said that while the ad was disappointing, it further highlights the relationship between amyloid beta removal and slowing clinical decline, but other research avenues should be considered.
“The future of Alzheimer’s treatment will be a combination of drugs targeting different aspects of the disease at different times, as well as lifestyle interventions,” the statement said.
HARD TO DIAGNOSIS
According to the World Health Organization, most of the 55 million people living with dementia worldwide are likely to have Alzheimer’s disease. By 2030, it is expected that 78 million people will be affected by dementia.
Alzheimer’s is difficult to diagnose, especially in its early stages.
German company Morphosys (MORG.DE) would have received tiered royalties of around 2% to 3% on future sales of gantenerumab due to its early role in the development of the drug. Its shares plunged 31%.
Royalty Pharma (RPRX.O) would have been entitled to about 3% to 4% of gantenerumab sales under a deal with Morphosys in 2021.
Data from a key late-stage study of Eli Lilly’s amyloid antibody drug donanemab is expected by mid-2023.
Reporting by Ludwig Burger in Frankfurt; Additional reporting by John Revill in Zurich and Khushi Mandowara in Bengaluru; Edited by Christopher Cushing, Bradley Perrett, Kirsten Donovan, Sriraj Kalluvila and Louise Heavens
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