patients to drop out of the trial, and data released Friday show one patient in the study with brain swelling also had a “seizure and loss of pulse.” While Biogen says the swelling is reversible, it remains a key issue to watch in further testing.
It now seems clear that solanezumab will not help people in decline, adding urgency to the search to treat millions of people—5.4 million in the U.S. alone—already showing symptoms of the disease. But that doesn’t mean solanezumab, or other drugs like it, can’t ever be useful.
Two major trials carry on, in part with funding from Lilly. Those trials, named A4 and DIAN-TU, are based on a more extreme version of the premise that inspired Lilly to gamble on solanezumab yet again: The earlier you intervene, the better the chance to treat the disease.
“Mild” Alzheimer’s is a misnomer, says Keith Fargo, director of scientific programs and outreach at the Alzheimer’s Association. “By the time a person can be said to have even mild dementia, the disease has already progressed fairly far along in their brain.”
A4 and DIAN-TU are going even earlier, testing people who are at high risk for the disease but have yet to show cognitive symptoms.
Because of solanezumab’s method of clearing free-floating amyloid protein, “this drug may be more appropriate for prevention rather than treatment,” says Morgan. “Ongoing studies will determine if treatment before symptoms will have greater impact, as predicted by many researchers.”
Investigators presenting the solanezumab data said Thursday night that would move forward despite the Expedition-3 results, said Snyder.
DIAN-TU is studying people with genetic mutations that almost certainly lead to Alzheimer’s at an earlier age—usually between the ages of 30 and 60. It’s easier to identify these people, because of the mutations, a luxury that researchers don’t have who are studying the more common “sporadic” form that affects people later in life.
A4, coordinated at the University of Southern California, is also testing people who aren’t yet showing cognitive decline or other Alzheimer’s symptoms. They are considered high risk because brain scans have captured amyloid buildup in their brains.
The two trials are studying very different groups of people. It’s quite possible one will produce positive data for very different reasons than the other—or not at all. As with Biogen, the A4 and DIAN-TU studies will produce final results in 2019.
If solanezumab fails to improve either group, it still won’t be the end of the amyloid hypothesis. Other research teams are studying the same high risk groups with other drugs that take aim at amyloid. For example, the same USC institute running the A4 trial is going to test drugs in people with no symptoms but signs of amyloid buildup in the brain. The drugs aim to intervene in the process that creates the amyloid fragments which form the sticky plaques.
Indeed, Snyder points out that despite all the uncertainty that remains, there is still a lot of funding for prospective Alzheimer’s treatments, and many types of drugs are being tested, data for some of which will also be presented this weekend. “There’s a lot happening in this space,” she says.
Alex Lash contributed to this report
