The search for an Alzheimer's disease treatment has been unsuccessful for the past 14 years.

The latest failure came in September, when Axovant said it failed a key late-stage trial for its drug, intepirdine.

Alzheimer's affects more than 5 million Americans, a number that's expected to balloon to 13.8 million by 2050. There are only four drugs that have been approved to treat the symptoms of the disease, and the most recent drug approval happened in 2003.

2017 in particular has been a tough year for Alzheimer's failures. In February alone, Lundbeck discontinued two of its trials, Merck discontinued one of its studies, and Accera failed a late-stage trial as well.

Axovant's trial results are the last major results to come out in 2017, with the next ones reading out in 2018 and a major wave of results expected in 2019.

Starting earlier

Research has determined that years - even decades - before a person might start showing symptoms, amyloid beta deposits in the brain that are characteristic of Alzheimer's disease can start to accumulate.

By the time we start seeing symptoms of dementia, researchers think, it might already be too late to do much.

So preventing any progression at that stage is something researchers are pinning a lot of hope on. There's one research effort going on in Colombia that's testing out an amyloid-related drug in an extended family with a rare genetic mutation that leads to early-onset Alzheimer's.

That study is in people who are still considered cognitively healthy, so if the drug is able to prevent cognitive decline, it could be a breakthrough.

What's ahead

According to PhRMA, there are more than a dozen experimental treatments that are still in phase 3, the latest stage of clinical trials before companies present their data to the FDA. Here are some of the ones to look out for in the next year or two.

  • VTV Therapeutics, a small company in North Carolina, has an Alzheimer's drug in late-stage trials called azeliragon that inhibits the RAGE receptor, ideally helping people with mild Alzheimer's delay cognitive decline. Its phase 3 trial is expected to wrap up in early 2018. The company got encouraging phase 2 results on the drug, which has been in the works for about 17 years. Even so, there's no guarantee it will succeed. "We are doing a sound and rigorous experiment," Larry Altstiel, VTV's chief medical officer told Business Insider.
  • Biogen's aducamumab, a BACE inhibitor, is going after the "amyloid hypothesis", or the idea that targeting beta amyloid deposits in the brain to clear them out is the way to go about treating the disease. It's expected to have results in 2019 or early 2020.
  • Lanabecestat, AstraZeneca's BACE inhibitor, is going be reading out in 2019. Like Biogen, it's going after the amyloid hypothesis.
  • Eli Lily's solanezumab failed a phase 3 trial in patients with mild dementia in November 2016, but has plans to keep trying the drug in pre-clinical stages of the disease to see if it works preventatively. Solanezumab is going after the amyloid hypothesis as well. While three trials have been disconnected, the fourth in this preventive setting is expected to have results in 2022.
  • In February, drugmaker Merck stopped its late-stage trial of verubecestat in patients with mild to moderate Alzheimer's, after a committee found that there was "virtually no chance of finding a positive clinical effect." The hope was to have the drug - a BACE inhibitor - stop the disease from progressing. Merck said it's still working on another late-stage trial for the drug to treat people with even earlier stages of the disease, and those results are expected in 2019.
  • Genentech has two Alzheimer's drugs in late-stage development, despite hitting setbacks. In February, Genentech and its partner AC Immune launched a phase 3 trial for crenezumab, another drug that's targeting amyloid deposits in the brain. It's expected to have data in 2020. The other is gantenerumab, a drug also targeting amyloid that failed earlier trials. The hope is that by increasing the dose, it might work. Genentech started a new phase 3 trial for gantenerumab in 2017.

This article was originally published by Business Insider.