Another step forward: The FDA, for the first time, granted permission for a tau PET ligand to proceed to a Phase 3 clinical trial.  What does that mean?

For background, please see my post from November 3, 2021, called “OK, so maybe we do have a marker.” 

A compound called “fluorine-18 APN-1607” (¹⁸F-APN-1607) is being developed as a PET ligand for PSP because of its affinity for the tau protein.  It specifically targets 4-repeat tau, the type found in the neurofibrillary tangles of PSP and corticobasal degeneration.  The ligand, which we’ll call simply “1607,” has passed safety testing and has been found able to distinguish PSP from its most likely diagnostic alternatives: Parkinson’s disease and the Parkinsonian variant of multiple system atrophy.  Of course, both of those are alpha-synucleinopathies, not tauopathies.  But 1607 can also distinguish PSP-RS from the two next-most-common kinds of PSP, called PSP-Parkinsonism and PSP-progressive gait freezing, and from corticobasal degeneration. 

Now the challenge is to see if 1607 can do those things better than a good neurologist, which means also a useful degree of accuracy in the early, diagnostically equivocal stages, not just after the disease is well-established, as in the trials to date .  The FDA-approved plan for the new trial will administer the scan to people with “possible” PSP, wait up to 18 months, and then compare those with positive scans to those with negative scans with regard to whether they’ve progressed to “probable” PSP.  The formal PSP criteria published in 2017 provide formal definitions of “possible” and “probable” PSP.  “Definite” PSP requires autopsy, and as part of its statistical analysis, the trial will analyze any patients, hopefully a minority, who come to autopsy during the 18-month period.

How long will this all require?  It will probably take a year to recruit all the patients, and the last patient will finish 18 months later.  Add a few months at the start for administrative issues and a few more at the end for data analysis, and we’re talking about 3 years.  But it’s progress, and the FDA has indicated that they would consider approving the product on the basis of this single Phase 3 trial, assuming the results are convincing. For most drugs, the FDA requires more than one Phase 3 trial.

Disclosure: The drug company behind 1607 is called Aprinoia Therapeutics, based in Cambridge, Massachusetts.  I serve as a paid consultant for them, advising in design of their trial.  I have no stock in Aprinoia or other financial interest in the success or failure of 1607.  In that spirit, I’ll also mention that another tau PET ligand, ¹⁸PI-2620, sponsored by a German company called Life Molecular Imaging, is close behind 1607 in the development pipeline and is showing similar utility.