With prospects of an early, accelerated approval for Roche’s Alzheimer’s disease candidate gantenerumab looking diminished, the drugmaker has launched a new four-year trial in the hope of building its case for the drug.
The new placebo-controlled SKYLINE study will enrol 1,250 people aged 60 to 80 with the earliest biological signs of Alzheimer’s – in other words signs of amyloid accumulation in the central nervous system – but no cognitive impairment.
The aim is to see whether the anti-amyloid antibody can slow disease progression over a four-year follow-up period, which means the readout of the study will still be several years away.
Roche is collaborating on the study – billed as a “secondary prevention” trial – with the Banner Alzheimer’s Institute, Massachusetts General Hospital and the University of Southern California Alzheimer’s Therapeutic Research Institute.
There had been speculation last year that Roche would move ahead with a quick filing for gantenerumab after Biogen got a controversial accelerated approval for Aduhelm (aducanumab) using amyloid clearance as a surrogate endpoint, although that was downplayed by the company.
It has since indicated it will wait for the results of two pivotal trials in early (prodromal to mild) Alzheimer’s – GRADUATE 1 and 2 – that are due to read out in the fourth quarter of this year, before making a decision on filing.
Eli Lilly meanwhile has already started a rolling application for its amyloid drug donanemab based on phase 2 results, but pushed back its plans to complete the filing after a draft decision by Medicare to limit coverage of Aduhelm and other drugs in the class to approved clinical trials. It will now wait for the results of the phase 3 TRAILBALZER-ALZ 2 next year.
Biogen and Eisai have also kicked off a rolling application for their second amyloid antibody lecanemab – ahead of the results of clinical data from the pivotal CLARITY AD study, also due in the second half of this year – and Eisai said today it had gone down the same route in Japan.
The decision to launch another phase 3 trial shows that Roche is willing to play the long game, and gamble more money on gantenerumab in the hope that the role of anti-amyloid drugs will become clearer in the coming years.
The track record of the drug isn’t encouraging however, as gantenerumab has previously failed a phase 3 trial in Alzheimer’s patients with early signs of cognitive impairment in 2014, causing Roche to shelve the drug, only to resurrect it three years later.
In 2020, it also missed the mark in a study involving people with an early-onset, inherited form of Alzheimer’s disease.
One factor in gantenerumab’s favour is that it can be administered by subcutaneous injection rather than intravenous infusion, allowing to be administered by the patient at home every one or two weeks. For comparison, Aduhelm is dosed once a month at a clinic at least 21 days apart.
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