Alzheimer's disease ranks as the No. 6 cause of death in the U.S. However, some estimates suggest that the disease should be ranked as the third-leading cause of death among older Americans, trailing only heart disease and cancer.

There is currently no cure for Alzheimer's disease. And there are only a few approved treatments. Over the last several years, drugmaker after drugmaker has reported failure in clinical studies of experimental drugs targeting the disease.

However, more progress is being made than you might think. At the Alzheimer's Association International Conference this past weekend, ResearchersAgainstAlzheimer's (RA2), a network of UsAgainstAlzheimer's (UsA2) that represents some of the world's leading Alzheimer's scientists, released its 2018 annual drug pipeline analysis. This report revealed five surprising things about Alzheimer's disease drug pipelines.

Physician holding small chalkboard with "Alzheimer's disease" written on it

Image source: Getty Images.

1. There are 31 Alzheimer's disease drugs in late-stage studies

Despite the notable clinical failures for companies like Eli Lilly and Merck, plenty of organizations continue to explore potential treatments for Alzheimer's disease. There are currently 31 Alzheimer's disease drugs in phase 3 clinical studies, according to RA2.

One of these late-stage candidates has especially attracted attention: Biogen's (NASDAQ:BIIB) aducanumab. Ever since Biogen announced encouraging results in 2015 from a phase 1 study of aducanumab, scientists, patients, and investors have watched the drug's progress. Market research firm EvaluatePharma ranks it as the No. 3 pipeline candidate in the biopharmaceutical industry. If successful in clinical studies, aducanumab could become the biggest Alzheimer's disease drug ever. 

2. There are 68 Alzheimer's disease drugs in phase 2 studies

Over twice as many Alzheimer's disease candidates are in phase 2 testing than are in phase 3. But while there are 68 phase 2 studies underway, that total includes one drug -- E2609 from Biogen and its partner Eisai -- that's in both phase 2 and phase 3 studies.

The count of Alzheimer's drugs in phase 2 could decrease soon, but for a good reason. Biogen and Eisai scored a surprise victory when the companies reported phase 2 results for BAN2401 earlier this month. Expect the drug to advance to late-stage testing in the not-too-distant future.

3. Up to 33 Alzheimer's disease drugs could reach the market by 2023

In theory, up to 33 drugs targeting Alzheimer's disease could reach the market by the end of 2023. This figure includes 25 drugs currently in phase 3 studies and eight drugs in phase 2 studies. It would be great if there really are 33 new Alzheimer's disease drugs on the market in a little over five years, but unfortunately, it's highly unlikely that will happen.

After all the years of research, only five drugs have obtained Food and Drug Administration (FDA) approval for treating Alzheimer's disease. Among all neurological conditions, on average fewer than one out of every two drugs that make it to phase 3 testing wins FDA approval. Roughly one out of seven neurological candidates in phase 2 clinical studies goes on to receive regulatory approval.

4. There's a much higher emphasis on tau drugs than in the past

There are two primary competing theories on what causes Alzheimer's disease. Some researchers think that the accumulation of amyloid plaque in the brain leads to the disease. Others believe that Alzheimer's is caused by another protein called tau. 

In the past, more research -- and more pipeline candidates -- have focused on the amyloid hypothesis. This is borne out by the fact that 10 of the candidates currently in phase 3 testing are amyloid drugs, compared to only two tau drugs. 

However, it's a different picture in the phase 2 pipelines: There are 12 amyloid drugs and 11 tau drugs. The leading focus in both phase 3 and phase 2, though, continues to be on drugs that regulate neurotransmitters -- chemicals that transmit messages between neurons.

5. Disease-modifying drugs outnumber symptomatic drugs 3-to-1

All of the currently approved Alzheimer's disease drugs only address the symptoms of the disease. The great news about the state of research today is that there are 74 candidates in phase 2 and phase 3 clinical studies that target modifying the disease, compared to 25 candidates that target only the symptoms of Alzheimer's.

The candidates that have generated the most excitement are these potentially disease-modifying drugs. While Biogen's pipeline has received the most attention, smaller biotechs like AC Immune (NASDAQ:ACIU) also have candidates with promising potential.

Challenges with the pipeline and beyond

Advancing drugs through the pipeline, especially in treating Alzheimer's disease, is tough enough on its own. But RA2 points to other challenges as well. Dave Morgan, a lead representative of the organization and a professor at Michigan State University, said: "Preparing the healthcare system to accommodate the efficient treatment of millions of Americans when a cure comes online is far from trivial. We need to start now." 

Another organization focused on Alzheimer's disease, the Global Alzheimer's Platform (GAP), worries that there could be a serious shortage of clinical trial sites that are capable of handling pending clinical trials. GAP believes that changes to how clinical trials are conducted for Alzheimer's disease are needed to address this issue in addition to an expansion in the number of clinical trial sites. 

For investors, a big challenge lies in how much confidence should be placed in promising early results. For example, good news for BAN2401 caused Biogen stock to soar. AC Immune's share price also jumped on the news, because investors saw the small biotech's lead candidate crenezumab as having a similar mechanism of action as BAN2401.

But while everyone hopes for breakthroughs in treating Alzheimer's disease, investors should be cautious. Unfortunately, there's still a long way to go. Stocks of biotechs that depend heavily on successful Alzheimer's disease candidates -- like both Biogen and AC Immune -- come with a lot of risk. 

Keith Speights has no position in any of the stocks mentioned. The Motley Fool owns shares of and recommends Biogen. The Motley Fool has a disclosure policy.