Big Pharma has tried and failed to cure Alzheimer's more than 200 times. The latest $18 billion flop leaves scientists hunting for a new path forward.

A promising, experimental Alzheimer's disease had a major failure on Thursday, when the drugmakers behind it announced they were cutting off most research efforts. Biogen lost roughly $18 billion of market value on the news. Watch Biogen trade in real time.Alzheimer's disease has no cure. Many drugs being developed for it have failed. Scientists don't fully understand Alzheimer's disease, which could be part of the problem. Biotech companies may need to understand the disease better to develop an effective drug.A promising but experimental Alzheimer's disease drug had a disastrous reversal of fortunes on Thursday, when two huge biotechs said they were largely giving up on it.The biotechs, Biogen and the Japan's Eisai, announced that they were cutting off most development efforts for the treatment aducanumab, after an independent committee said that two advanced research trials testing out the drug weren't showing signs of success. The news took roughly $18.4 billion of Biogen's market value with it, as the shares plummeted.A cure for Alzheimer's, a devastating disease that affects memory and robs individuals of their ability to talk and move, has long eluded pharmaceutical and biotech companies. The disease affects at least 5 million Americans now, and the number is expected to jump to nearly 14 million by 2060, as the US population ages.The Alzheimer's Association estimates that the cost of caring for individuals with Alzheimer's and other forms of dementia comes to about $290 billion a year. The disease is among the top causes of death in the US.A cure or effective treatment for the disease would immediately find a huge market. But notably, despite huge investments, there have been no new medications for Alzheimer's since 2002, according to Datamonitor Healthcare. At least 206 potential treatments have flopped in trials, Datamonitor found.And the latest development shows that biopharmaceutical companies still have little idea how the disease works, or how to fight it. The failure casts a pall over the more than 100 products being developed for Alzheimer's today, including two other promising Alzheimer's disease drugs from Biogen and Eisai.“This disappointing news confirms the complexity of treating Alzheimers disease and the need to further advance knowledge in neuroscience,” Biogen CEO Michel Vounatsos said in a statement. Read: A $63 billion biotech is returning to the scene of its worst failure in search of new treatments for a deadly muscle disorderMizuho analyst Salim Syed said this news casts doubt on the entire dominant scientific approach to the disease, termed the “beta-amyloid” hypothesis, after proteins thought to be important in driving the disease.“It's clear now, Aducanumab is dead, and we'd argue so is the beta-amyloid hypothesis,” he said. Scientists don't completely understand Alzheimer's disease, including why the disease typically affects older adults. But it's likely that genetic, lifestyle and environmental factors play important roles in why individuals over age 65 most commonly get it, the National Institutes of Health notes.Read more: Biogen is crashing after scrapping its late-stage Alzheimer's drug trialsWhat this means for 'beta-amyloid'One dominant explanation has pointed to a buildup of “beta-amyloid” protein fragments in the brain as a driver of the disease. The Biogen and Eisai drug aducanumab honed in on those protein fragment. So does another experimental Alzheimer's disease medication from the two companies, BAN2401, and so did a lot of other failed Alzheimer's disease drugs.But experts now think the mechanism behind Alzheimer's disease may be much more complex. Read more: The search for new Alzheimer's treatments just faced another setback — and now everything hinges on an approach that's already run into trouble“The problem is that we don't know what the problem is,” Dr. Laura Boylan, a New York-based neurologist who treats individuals living with Alzheimer's disease, told Business Insider. Boylan said that the patients who she sees don't have high hopes about some new medicine coming along.Moreover, the field may need a better understanding of Alzheimer's disease, she said, because basic science about how a disease works guides how drugs are developed. “If you realize that stroke is caused by high blood pressure, then you can lower blood pressure,” she said. Without that, “you don't know how to approach it.” Beta-amyloid is probably still involved in Alzheimer's disease, but other factors could be too, including another protein called tau, factors affecting blood flow, and more. Cantor Fitzgerald analyst Alethia Young described the beta-amyloid theory as “meaningfully impaired after today's setback.” “We believe aducanumab had the best shot of working of all of the amyloid beta programs,” she said. Other drugs are 'more risky'Young also called other advanced experimental Alzheimer's disease drugs, including BAN2401 and elenbecestat, a different type of drug called a BACE inhibitor that is also from Biogen and Eisai, “more risky.” A major question now is what drug companies do from here on.Biogen, for its part, told Business Insider in a statement that “it is premature to draw any conclusion before we have fully analyzed the data,” which is what it's now doing. Asked what this development means for BAN2401, the biotech also referred to its continuing analysis efforts. But investors are likely to lose confidence because of the “high-risk nature of the science,” Jefferies analyst Michael Yee said, calling the latest news exactly what they had feared could happen. Yee himself, though, noted that all Alzheimer's drugs are not created equal, and there are “different science and genetics around different targets,” suggesting there may be a path forward for other types of Alzheimer's disease drugs.