The FTD research landscape is on the verge of major developments. For the first time, a Phase 3 trial has been completed for a potentially disease-modifying treatment for a type of genetic FTD, with results expected in 2025.

As we wait for these Phase 3 trial results, we are taking time to summarize current updates in trials for a type of genetic FTD, as their progress may have impacts for all people impacted by FTD as well as all FTD researchers, healthcare providers, and investors.

Approximately 40% of FTD cases are currently thought to be familial or have genetic underpinnings. These trials all tackle the progranulin hypothesis – the idea that for people with FTD caused by GRN variants, restoring progranulin levels will reduce FTD pathophysiology and symptoms.

There are other major genes that contribute to FTD, such as C9orf72 and MAPT. While there are trials ongoing or emerging which may enroll people with FTD with C9orf72 variants, we focus here on GRN as the genetic target furthest along in trials. There are also trials on other genes and aberrant proteins that are being tested in people with related diseases such as ALS and Alzheimer’s, which may hold promise for genetic and sporadic forms of FTD. While significant drug development progress is being made for specific types of FTD, there will be learnings and progress that will benefit all.

Below are summaries of the status of six active FTD trials as of the time of publication, in alphabetical order by sponsor.   

Important note: AFTD is an informational resource and does not specifically encourage or discourage patient participation any specific clinical trial. 

Sponsor: Alector (with GSK) 

Study: INFRONT-3 (Phase 3) 

Drug: AL001 (Latozinemab) – anti-sortilin monoclonal antibody; intended to block sortilin-mediated progranulin degradation  

Delivery route: Intravenous  

Update: Phase 3 enrollment is complete and results are expected by the end of the 2025 calendar year. Phase 2 updates were previously provided.  

Clinicaltrials.gov: NCT04374136 

Sponsor: AviadoBio 

Study: ASPIRE-FTD (Phase 1/2) 

Drug: AVB-101 – GRN AAV9 gene therapy; intended to increase progranulin levels by delivering a functional GRN gene into the brain  

Delivery route: Intrathalamic infusion  

Update: Dosing is completed of a second cohort  in Phase1/2 and dosing of a third cohort is intended in Q3 2025, with the expectation that early biomarker data will be shared in 2026.  

Clinicaltrials.gov: NCT06064890  

Sponsor: Denali Therapeutics & Takeda Pharmaceuticals 

Study: Phase 1/2 

Drug: TAK-594/DNL593 – recombinant progranulin combined with protein transport vehicle technology;  intended to increase progranulin levels by delivering the progranulin protein across the blood-brain barrier  

Delivery route: Intravenous 

Update: Phase 1 part A data dosing of health volunteers was previously reported and part B dosing of people with GRN-related FTD is ongoing.  

Clinicaltrials.gov: NCT05262023   

Sponsor: Passage Bio 

Study: upliFT-D (Phase 1/2) 

Drug: PBFT02 – GRN AAV1 gene therapy; intended to increase progranulin levels by delivering a functional GRN gene into the brain  

Delivery route: Injection into the cisterna magna  

Update: Interim data has been announced from Dose 1 in people with GRN variants and further interim data from Dose 2, is expected in 2026. Future cohorts are planned to also include participants with FTD-C9orf72.

Clinicaltrials.gov: NCT04747431 

 Sponsor: Prevail Therapeutics, a wholly owned subsidiary of Eli Lilly  

Study: PROCLAIM (Phase 1/2)  

Drug: PR006 – GRN AAV9 gene therapy; intended to increase progranulin levels by delivering a healthy GRN gene into the brain 

Delivery route: Injection into the cisterna magna 

Update:  Interim results for Phase 1/2 were published in 2024 and recruitment is ongoing. 

Clinicaltrials.gov: NCT04408625 

  Sponsor: Vesper Biotechnology  

Study: SORT-IN-2 (phase 1/2) 

Drug: VES001 – small molecule; intended to cross the blood-brain barrier and inhibit sortilin-mediated progranulin degradation
Delivery route: Oral  

Update: Phase 1 data in healthy volunteers was previously reported and Phase 1b/2a has reached enrollment milestones in asymptomatic patients who are carriers of GRN variants, with results expected in the second half of 2025. 

Clinicaltrials.gov: NCT06705192 

For the most up-to-date information on these trials, consider referring patients and families to enroll in the FTD Disorders Registry, which can keep them informed about new and emerging research opportunities; or referring them to AFTD’s HelpLine (info@theaftd.org, 866-507-7222); or referring them to clinicaltrials.gov. Participation in the Registry can also encourage drug development by documenting the numbers of affected people.AFTD has created resources on FTD Genetics and gene therapy, and is committed to enabling and strengthening efficient and informative FTD clinical trials. Visit our For Researchers page for more information about working with us as a researcher. 

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