- Trials show little benefit, but without statistical validity
- Roche’s setback leaves Biogen, Eisai as leaders in the field
- It falls to Roche appointed CEO to revive development fortunes
- Roche shares down 3.4%, development partner Morphosys down 29%
Nov 14 (Reuters) – Roche’s ( ROG.S ) Alzheimer’s drug candidate failed to be shown to slow the progression of dementia in two drug trials, leaving rivals Biogen ( BIIB.O ) and Eisai ( 4523.T ) as leaders in a high -stakes race to launch a treatment for the memory-robbing disease.
Roche said in a statement on Monday that the twin studies known as Graduate 1 and 2 had not met their main goal of showing that the drug gantenerumab could preserve abilities such as memory, problem solving, orientation and personal care in patients suffering from early stages of Alzheimer’s. disease.
The Swiss drugmaker conducted two identically designed studies, each involving around 1,000 participants, who were examined and questioned by doctors over more than two years. In each study, volunteers were randomly assigned to either the injectable antibody 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 placebo, but these results were not statistically significant, 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 breach as “unequivocal”.
Berenberg analysts had pegged a 50% probability of gantenerumab hitting the $10 billion mark.
Roche shares fell 3.4% to their lowest in nearly seven weeks.
Shares of U.S. drugmakers Biogen Inc ( BIIB.O ) and Eli Lilly and Co ( LLY.N ), which are developing rival treatments for Alzheimer’s, rose 3.8% and 2.3% respectively in premarket trading.
Analysts have said the fallout from the trial will affect stock market confidence in Roche’s research prowess, especially after lung cancer immunotherapy hope tiragolumab failed in trials earlier this year, knocking the company’s shares.
“The development pipeline has disappointed a little too often to keep the stock on a list of favorites,” analysts at Luzerner Kantonalbank said in a research note.
Gantenerumab was designed to bind to aggregated forms of beta-amyloid and clear brain amyloid plaques, which are thought to play a crucial role in the slowly progressive 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, CEO 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 marked by a long list of failed trials.
But Biogen in September scored a surprise success with an experimental Alzheimer’s drug it co-developed with Eisai, rebuilding confidence among industry executives and researchers in its beta-amyloid approach.
Biogen and Eisai said at the time that their drug candidate lecanemab had slowed the progression of the brain-damaging disease by 27% compared with a placebo in a large study of patients in the early stages of Alzheimer’s.
Roche’s trial failure “takes out the biggest 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 buildup, among other differences in the molecules and trial designs.
Roche only released the main results of the trials on Monday. It plans to present detailed data at the Clinical Trials on Alzheimer’s Disease conference in San Francisco on November 30.
Rachelle Doody, Roche’s head of neurodegeneration, said she was very disappointed, adding that trial measures to remove amyloid were also lower than hoped.
“We want to show that there is a correlation between the reduction of amyloid and the clinical outcomes. It’s just that when you don’t get the amyloid reduction you expected, you won’t get the clinical outcome you expected,” she told Reuters.
The global Alzheimer’s Association said the readout, while disappointing, further illustrated the relationship between removing beta-amyloid and slowing clinical decline, but other research approaches should be considered.
“The future of Alzheimer’s treatment will be a combination of drugs that target different aspects of the disease at different times, as well as lifestyle interventions,” it said in a statement.
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 in the early stages.
Germany’s Morphosys ( MORG.DE ) would have received royalties of around 2% to 3% on future gantenerumab sales from its early role in developing the drug. The shares plunged 31 percent.
Royalty Pharma ( RPRX.O ) would have been entitled to about 3% to 4% of gantenerumab sales under a 2021 deal with Morphosys.
Data from a pivotal trial of Eli Lilly’s amyloid-targeted antibody drug, donanemab, is expected in mid-2023.
Reporting by Ludwig Burger in Frankfurt; Additional reporting by John Revill in Zurich and Khushi Mandowara in Bengaluru; Editing by Christopher Cushing, Bradley Perrett, Kirsten Donovan, Sriraj Kalluvila and Louise Heavens
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