You may know that a number of ongoing clinical trials are evaluating treatments with the potential to slow, or even stop, the progression of FTD. (Some of those trials are currently recruiting participants.) This includes Alector’s trial for latozinemab, which expects Phase 3 results some time in 2025. But what is a Phase 3 trial and what do its results mean?

First, let’s define what happens in a clinical trial. Clinical trials are designed to determine the safety and effectiveness of new medical interventions, such as medications to treat FTD. Interventions generally go through several clinical trial phases, each of which includes a larger number of participants who are evaluated for a longer period of time. Clinical trials only progress to the next phase if the drug is shown to be safe and effective. If it isn’t, the trial ends.

Phase 3 is the final step of the journey: the largest and most critical phase in evaluating new treatments before they can be approved for public use. (Even after a drug is approved, scientists and healthcare providers continue to monitor the drug’s safety.)

After a Phase 3 trial concludes, scientists review the results to see how the drug performed relative to the overall trial’s “endpoints,” or the criteria that were chosen before the trial to evaluate the treatment. Endpoints may include whether the drug resulted in biological changes or whether it improved participants’ quality of life. Scientists also determine if the drug caused any adverse health effects, and, if so, they note the severity of those adverse effects. 

After the trial has concluded and the results have been fully analyzed, they are often published and posted on ClinicalTrials.gov, a website maintained by the U.S. Department of Health & Human Services. The biopharmaceutical company that conducted the trial will also typically issue a press release containing its final results; AFTD will share updates when appropriate. 

What kind of results can occur? 

At the end of a clinical trial, the scientists may find that the drug did not significantly improve the trial’s endpoints. This sounds negative. But even when a trial does not achieve its goals, it still provides a great deal of information, such as what works and does not work to treat FTD.  

Results may also be inconclusive – neither clearly positive nor negative – and therefore require further study and/or additional input from the community. 

But the results could bring good news for families facing FTD – positive or promising outcomes. In that case, the company that conducted the trial can formally ask the U.S. Food and Drug Administration (FDA) for approval by submitting a New Drug Application or a Biologics License Application. The FDA then evaluates all the data on the safety and therapeutic benefit of the drug or treatment before deciding whether to award its approval. 

If approved, the FDA determines the drug’s label, which includes information such as how to use the drug, who it is for, and the stage of disease it is approved to treat. In many cases, the FDA will ask the sponsor re-review it before it gives approval, which may require additional studies and/or data-gathering. The FDA’s website contains more information on the drug review and approval process. 

There is a separate but similar process that takes place with other regulatory agencies outside the U.S. if the drug sponsor pursues drug approval in other countries. If the drug is approved, there are subsequent steps where payers (e.g., insurance providers) decide on their coverage.  

A number of pathways make it easier to conduct research in diseases such as FTD, where there are currently no approved therapies. These include Fast Track , Breakthrough Therapy, and Priority Review as well as the Accelerated Approval Program. All of these initiatives are intended to bring drugs to market more quickly while maintaining the safety and scientific rigor of the clinical trials.  

Deciding whether to participate in a trial 

It can be difficult to keep track of the ever-changing FTD clinical trial landscape. AFTD recommends all people impacted by FTD – persons diagnosed, family members, care partners, friends, and healthcare professionals – enroll in the FTD Disorders Registry. The Registry can keep you up to date on new clinical trials (and other types of research studies) as they emerge and allows some people to participate in critical survey research from the comfort of home. One of the primary barriers to conducting research in FTD is finding available participants, so every interested volunteer matters! You can learn more about clinical trials and things to consider when determining if a clinical trial is right for your family on AFTD’s clinical trials web page.  

For people interested in learning more about the genetics of FTD and whether you or your family members may be eligible to participate in one of the ongoing genetic FTD trials, consider speaking to a genetic counselor. More information on finding a genetic counselor can be found on the Genetic Counseling page on the AFTD website.  

People impacted by FTD are a critical piece of the scientific puzzle. Regardless of whether you’re eligible or interested in participating in a clinical trial, there are a number of additional ways you can help the field move forward towards a treatment. Learn more about how you can take part in research on our ways to participate web page. Learn more about the role of the community in drug development by watching the webinar AFTD and You: Partners in Drug Development. 

Why the focus on genetic FTD? 

Studies furthest along in development focus on genetic FTD.  In those cases, scientists are more confident that the FTD diagnosis is correct, they have a better understanding of the underlying causes, and they have the tools to intervene in the disease process.  

Many of these trials, including Alector’s, are focused specifically on FTD caused by the GRN gene (FTD-GRN). FTD-GRN is caused by variants in the GRN gene that prevent it from making progranulin, a protein necessary for brain health. Researchers are testing treatments to increase the amount of progranulin in the brain using different methods, such as protein replacement and gene therapy, or by reducing processes that remove progranulin from cells.  

Additional active clinical trials address FTD-causing variants in other genes, such as C9orf72. AFTD is also working to see how interventions being tested in related conditions, like Alzheimer’s and ALS, can be applied for FTD-causing genes.  

There is active research taking place earlier on in the drug development pipeline for rarer FTD genes and for sporadic FTD. What we are learning from these furthest along trials, such as effective ways to clear harmful protein aggregations, will have implications for all types of FTD, both genetic and apparently sporadic cases.

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