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 The Swiss drugmaker's treatment was tested in patients with
mild-to-moderate forms of Alzheimer's, a fatal, brain-wasting
condition that gradually robs patients of their ability to think and
care for themselves.
Results of a Phase II study involving 431 patients found crenezumab
failed to significantly slow cognitive and functional decline
compared to placebo, missing the study's two main goals, Roche said
in a statement on Wednesday.
But an exploratory analysis of patients with a milder form of the
disease who received a higher dose of crenezumab via an intravenous
infusion showed a statistically significant reduction in cognitive
decline, Roche said.
Carole Ho, director of Early Clinical Development at Roche's biotech
unit Genentech, told Reuters she was encouraged by the data, even
though it missed its main goals, since it demonstrated that treating
the disease earlier could increase the benefit.
Ho said Roche would decide on any future plans for additional
clinical studies following an analysis of the data in conjunction
with health authorities.
Analysts had anticipated limited success for crenezumab, after a
similar treatment from Pfizer Inc and Johnson & Johnson called
bapineuzumab, and solanezumab, a drug from Eli Lilly and Co, failed
in late-stage trials.
All three drugs work by blocking the toxic protein beta-amyloid that
forms plaques in the brain believed to signal the onset of the
disease.
Another protein called tau that forms twisted fibers and tangles
inside the brain is also considered to be a possible culprit.
Sanford C. Bernstein analyst Tim Anderson said the positive impact
in patients with mild Alzheimer's lent credence to the beta-amyloid
hypothesis but added this would need to be vetted further in large
Phase III trials.
But some researchers were skeptical about pursuing the amyloid
theory.
"This failure combined with a dozen or so prior failures are
definitely a blow to the amyloid hypothesis as we originally
proposed it," said P. Murali Doraiswamy, a professor at the Duke
Institute for Brain Sciences. "The hypothesis needs to be changed
and we need to pursue non-amyloid targets, or else we will suffer
more failures."
Based on the results of the trial, the odds of crenezumab gaining
approval for treating mild to moderate Alzheimer's are very low, he
added.
Shares in Roche closed down 0.6 percent at 266.40 Swiss francs,
underperforming a slightly firmer European healthcare sector index
EARLIER TREATMENT
The findings add to a string of data suggesting the best hope is
testing drugs much earlier in the process before patients' brains
are wrecked by Alzheimer's.
Lilly has since started a new clinical trial focusing only on
patients with mild signs of the disease. Other trials are already
underway testing people who have not yet shown any symptoms of
Alzheimer's to try and gauge whether early intervention can prevent
or slow the disease.
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Crenezumab, which was licensed from Swiss biotech company AC Immune
in 2006, is also being tested in a U.S. government-backed trial in a
group of Colombians with a genetic mutation that causes them to
develop Alzheimer's early. Results of that trial are due in 2020.
A second Alzheimer's drug from Roche, known as gantenerumab, is also
being investigated in a late-stage trial with patients who are yet
to develop any signs of the disease.
Roche said a smaller Phase II biomarker study also showed an effect
of slowing cognitive decline in patients with a milder form of the
disease. Details of this study will be presented at the Clinical
Trials in Alzheimer's Disease meeting in November.
Jeffrey Cummings, director of the Cleveland Clinic Lou Ruvo Center
for Brain Health, who presented the crenezumab data at the
Alzheimer's Association International Conference in Copenhagen, said
he was encouraged by the consistent benefit seen in the most mild
patients.
"It has been very difficult to have any convincing evidence of a
treatment effect in Alzheimer's Disease," Cummings said. "When you
see this kind of consistency across two trials then you would
definitely want to advance a drug in a trial that focuses
specifically on very mildly affected patients."
The drug was well tolerated with only one case of vasogenic edema, a
brain swelling side effect seen in similar drugs, allowing
crenezumab to be administered at higher doses, Roche said, though
patients taking the medicine did have a higher incidence of
pneumonia than those on placebo.
At lower doses when crenezumab was administered through an injection
beneath the skin no significant benefit was seen even in milder
patients, the results revealed.
Alzheimer's - the most common form of dementia - already afflicts 44
million people worldwide and this figure is set to triple by 2050,
according to campaign group Alzheimer's Disease International.
Unlike heart disease and cancer, which have seen major strides in
drug development, no new therapies have been approved to treat
Alzheimer's in a decade, according to a recent study by researchers
at the Cleveland Clinic. Current drugs only treat symptoms despite
years of research.
A startling 99.6 percent of clinical trials in Alzheimer's failed
between 2002 and 2012, the Cleveland Clinic study found.
(Reporting by Caroline Copley; Editing by Elaine Hardcastle and
Jonathan Oatis)
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