Tag Archives: AZP-2006

Two new drugs rarin’ to go

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Some good news for those seeking to enroll in a PSP drug trial: The PSP Platform (PTP) is scheduled to start enrolling in the first quarter of 2026. The first two drugs will be the AADvac1 and AZP-2006. The first is a vaccine that stimulates the immune system to make its own anti-tau antibodies.  The second boosts the part of the brain’s garbage disposal system most relevant to PSP.

The third drug is still being finalized with its Pharma sponsor and some points in the study protocol await approval by the FDA.  Only then could the results potentially be used to support a new drug application.  These delays explain the start-up postponement from December 1, 2025 listed in ClinicalTrials.gov to early 2026.

As described in more detail in previous posts here and here, the PTP is a group of about 50 centers in the US led by neurologists at UCSF, UCSD and Harvard.  They have created an infrastructure to test up to three drugs simultaneously, each in its own set of 110 participants.  A major advantage of such a plan is that all three trial groups share the same placebo group.  That way, each participant has only a 25% chance of being assigned to placebo.  The other obvious advantage is cost savings, which could lower the bar for a company to give its drug a go.  The trial is heavily subsidized by a grant from the NIH budgeted for about $14.5 million this year and similar amounts annually through 2029. https://reporter.nih.gov/project-details/11160498

The names and locations of the approximately 50 participating sites across the US have not been announced, but those interested should keep an eye on the ClinicalTrials.gov page https://clinicaltrials.gov/study/NCT07173803 or wait a few days and contact the study’s central enrollment center at 213-821-0569 or psp-participate@usc.edu at the University of Southern California. But perhaps the best option is simply to register with CurePSP for updates on the trial’s status.

Reality check: As for most PSP drug trials, the hope is to slow the rate of progression. The PTP is designed to be able to detect a slowing relative to the placebo group of 33% or better over the 12-month period of the trial.  The trial’s design is based on assumption that the drug would not improve the symptoms – it would at best slow down the pace at which they worsen.  But if all goes well, that could mean many months or even a couple of years of good-quality life.  An even better outcome to hope for is that one of the drugs would work well enough to prevent progression altogether (“100% slowing”), maintaining the present level of symptoms for the remainder of whatever would have been the person’s lifespan without PSP. 

A 33% slowing is a very realistic hope. That 100%-slowing scenario is only a distant hope, but one that’s theoretically possible. And hope does matter.

For once

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Some excellent news for you today.  The orally administered drug AZP-2006 has shown early signs of slowing the progression of PSP. (Yes, you heard right!)

My blog post from May 9 of this year brought news that a small, open-label, Phase 1 study of AZP-2006 seemed to have slowed the progression of PSP by 31 percent.  Now, the drug has completed a small, double-blind, Phase 2a trial with even better results: In the 11 patients receiving 60 mg per day, the worsening in the PSP Rating Scale score over the 3 months of the double-blind phase was a third slower than in the placebo group (identical to the result of the uncontrolled Phase 1) and in the 13 patients receiving a loading dose of 80 mg on the first day and then 50 mg per day, the apparent worsening was two-thirds slower.  

It’s important for you to understand, and the authors repeatedly emphasize, that these results were not statistically significant, meaning that they could be the result of a random fluke.  There were also some minor differences among the three patient groups (placebo, 60 mg, and 80 mg then 50 mg) at the study’s baseline that theoretically could have explained the results.  A larger, Phase 2b study could confirm the result while having the statistical power needed to compensate for any “baseline bias” among the treatment groups. 

The trial included a 3-month open-label extension. That’s where the participants on placebo for the first 3 months were offered the opportunity to convert to the active drug at 60 mg per day, while those initially on the active drug could opt to continue it.  Over months 4, 5 and 6, the rate of decline of the formerly-placebo group slowed down noticeably.  The other important result is that the drug showed itself to be safe and well-tolerated over the entire 6 months.

The publication’s first author is Jean-Christophe Corvol, MD, PhD, a very well-regarded, senior neurologist I know at the legendary Hôpital Pitié-Salpêtrière in Paris.  The senior (i.e., last-named) author is Luc Defebvre, MD, PhD, at Lille University. Six of the other 16 authors are staff researchers at the sponsoring drug company, AlzProtect, of Lille, France.

In this graph, the vertical axis is the worsening in terms of the 100-point PSP Rating Scale.  EOT is end of the double-blind part of the trial at Day 84.  Thereafter, all participants received active AZP-2006.  Note that both active-drug groups progressed more slowly than the placebo group over the first 3 months; and on active drug, the participants formerly on placebo may have slowed their progression rate. The vertical line segments represent standard deviations of the mean. (From:  Corvol JC, Obadia MA, Moreau C, et al. AZP2006 in progressive supranuclear palsy: outcomes from a Phase 2a multicenter, randomized trial, and open-label extension on safety, biomarkers, and disease progression. Movement  Disorders. 2025 Sep 27. doi: 10.1002/mds.70049. PMID: 41014124)

So, when will the Phase 2b study start?  My May 5, 2025 post reported on the “PSP Platform,” (PSPP) an NIH-supported collaboration among dozens of U.S. academic centers to perform Phase 2b trials on up to three drugs simultaneously using one placebo group.  One of the first three drugs, in fact, is AZP-2006.  Last I knew, the PSPP was expected to start late this year, but it’s now almost October and I’ve heard nothing further other than that some details remained to be ironed out with the FDA. That trial would take about 6-12 months to recruit and then another 12 months for the last patient to finish, then at least a couple of months to analyze the data. 

So, how does AZP-2006 work?  I’ll plagiarize my own May 9 blog post, along with its “Nerd Alert!” warning that this gets technical:

The main mechanism of action of AZP-2006 is at the lysosomes, one of the cell’s garbage disposal mechanisms, where it acts specifically at the lysosome’s prosaposin and progranulin pathways. Prosaposin is the metabolic precursor (a “parent molecule” cleaved by enzymes to produce the active molecule) of the saposins, a group of proteins required for the normal breakdown of various types of lipids that are worn out or over-produced or defective from the start. Progranulin is the precursor, as you’d guess, of granulin, which, like saposin, is involved in function of the lysosomes. But progranulin addresses disposal of proteins, not lipids. In mouse experiments, the drug also enhances the production of progranulin, mitigates the abnormal inflammatory activity in tauopathy, reduces tau aggregation, and stimulates the growth or maintenance brain cell connections.

Bottom line: This very small, Phase 2a trial was designed to show safety, not efficacy, and its slowing of PSP progression did not nearly achieve statistical significance nor exclude potential sources of random bias.  But the magnitude of the (apparent) effect make this excellent news for those with PSP, present and future.

A French Swiss Army knife

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My last post was about AADvac1, one of the three neuroprotective drugs set to inaugurate the PSP Trial Platform (PTP) later this year. Today’s post is about the second drug, AZP-2006. The third drug has not yet been finalized, but at a conference in London last week, Dr. Adam Boxer, the leader of the PTP, said it will be revealed soon.


The PTP trials are all Phase 2a, meaning that they’re designed primarily to assess safety and tolerability. However, they do include enough patients, typically about 100 or 200, to detect drug benefit if any indeed exists. The benefit would be in the form of slowing of the rate of progression of PSP as measured by a newly abridged version of the PSP Rating Scale. The PTP will recruit one placebo group to serve as a comparator for all three active-drug groups.


An unpublished Phase 1 PSP trial in 36 people with no placebo group found a 31% slowing of the PSP Rating Scale progression relative to placebo groups in previous PSP drug trials. I hasten to add that comparing the results of active drug in an uncontrolled study to the placebo group in a completely different study is a minefield. So, let’s not jump to conclusions about the efficacy of this drug. All we can say is that the result justifies further investment and study.


That said, I’ll point out that in placebo-controlled Phase 2b and Phase 3 trials, a slowing of 20% or 25% relative to the placebo group is often considered adequate to consider the drug for approval.
AZP-2006 is administered as an oral liquid, which is more convenient than the intravenous, subcutaneous or intrathecal (into the spinal fluid) routes of some of the other current experimental PSP drugs. But of course, oral liquids can be a major issue for those with PSP, though it seemed not to cause any dropouts or serious adverse effects among the 36 patients in the Phase 1 trial. I don’t know if the AZP-2006 oral solution is compatible with the commonly used gelatin- or starch-based drink thickeners. The PTP trial will be confined to patients in early to moderates stages of disability, without the more pronounced swallowing difficulty of the later stages.


Nerd Alert: The main mechanism of action of AZP-2006 is at the lysosomes, one of the cell’s garbage disposal mechanisms, where it acts specifically at the lysosome’s prosaposin and progranulin pathways. Prosaposin is the metabolic precursor (a “parent molecule” cleaved by enzymes to produce the active molecule) of the saposins, a group of proteins required for the normal breakdown of various types of lipids that are worn out or over-produced or defective from the start. Progranulin is the precursor, as you’d guess, of granulin, which, like saposin, is involved in function of the lysosomes. But progranulin addresses disposal of proteins, not lipids. In mouse experiments, the drug also enhances the production of progranulin, mitigates the abnormal inflammatory activity in tauopathy, reduces tau aggregation, and stimulates the growth or maintenance brain cell connections. The company has not published or otherwise released details of the mouse work and if they know the details of these mechanisms of action, they’re keeping them secret for now.
One hereditary type of familial frontotemporal dementia where TDP-43 is the mis-aggregating protein is caused by mutations in the progranulin gene. However, progranulin mutations seem not to be related to PSP.


AZP-2006 was developed by Alzprotect, a company headquartered in Lille, France that was started in 2007 and has no approved drugs as yet. Here’s a page from the company’s website. It includes a nice video with an artist’s conception (or a PR consultant’s dream) of how the drug works.


AZP-2006 may be the most likely to succeed among the currently announced anti-PSP candidates in or nearing clinical trials. That’s because it addresses multiple important cellular abnormalities simultaneously (see the Nerd Alert above), something that many of the experts feel will be sine qua non for any successful PSP neuroprotective drug.

Two new drugs get a platform

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This could be the best news ever in the history of clinical drug development for PSP.


Last week, I attended the Global Tau meeting in London as a representative of CurePSP. Plenty of excellent research was presented, but most of it was laboratory work that would be difficult to relate to the direct concerns of most of this blog’s readers. But there were some clinical advances, and here’s a big one.

Dr. Adam Boxer of the University of California, San Francisco is the project leader for the PSP Trial Platform (PTP). My Oct. 27, 2023 post briefly mentioned that the PTP had just been funded by the NIH. A trial platform is an organization, in this case about 50 study sites throughout North America, that invites multiple pharmaceutical companies to simultaneously allow it to test their trial-ready experimental drugs. The big news last week was Dr. Boxer’s announcement identifying the first two drugs and that enrollment should begin in late 2025.

One drug to be tested will be AZP-2006, from Alzprotect, based in Lille, France. It addresses tau accumulation and neuro-inflammation. The other is AADvac1, from Axon Neuroscience, based in Bratislava, Slovakia. It is an active vaccine directed against the tau protein. More on those drugs in a future post. Both will be Phase 2a trials, meaning that the emphasis will be on safety and tolerability, though efficacy will be detectable if it’s dramatic. The PTP has a candidate for a third company/drug in the wings awaiting final contract negotiations.


The double-blind phase for each drug would be 12 months, followed by an open-label phase, where the participants on placebo will be offered active drug. The primary efficacy outcome measure will be a version of the PSP Rating Scale abridged from its original 28 items to the 15 items best suited to daily disabilities.


Advantages of platform trials over traditional single-drug trials:
• Only one central coordination, technical and statistical staff is needed. This makes drug testing more economical in terms of both money and time, lowering the bar for smaller companies to test promising treatments.
• Only one placebo group is needed and more active-drug arms can be added in the future. So, if a traditional trial offers only a 50% chance of receiving active drug, a platform trial testing three drugs would offer a 75% chance of being assigned to active drug.
• Once the platform is up and running, there is no delay for test site recruitment, contracting and training. This further reduces the costs and allows a new drug to be smoothly slotted into a vacated spot.
• It’s possible to make the three drugs’ trial protocols relatively uniform, allowing the results to be compared with greater confidence than would be possible if each had been tested in separate projects.
• The availability of a completed control group facilitates an interim analysis (a peek at the incomplete data under strict confidentiality rules) to determine if continuing that drug’s trial would be futile. If the result is unfavorable, this saves time, money and most important, drug side effect risk for future participants. Such a drug could be withdrawn from the PTP and another drug could take its place.


The other Principal Investigators working with Dr. Boxer are Dr. Anne-Marie Wills at Massachusetts General Hospital, Dr. Irene Litvan at UC San Diego and Dr. Julio Rojas of UCSF. The NIH has committed $70 million over five years to this project and the participating drug companies would also contribute substantially (though much less than if they had mounted trials on their own). Dr. Boxer told me that as of last week, in late April 2025, the NIH funding had not been affected by the recent Federal research budget cuts, but we’re all holding our breath on that.