r/LongCovidTrials

There are now 2 studies that have been published about the use of weekly Rapamycin (LDR) for MECFS, with encouraging yet small results.
But:
- Other studies about the use of LDR for dementia show there is an increase of neurofilaments (Nfl), a biomarker of neurons destruction, associated with a lower decrease in brain volume (which is very different from neurons quantity).

- They claim it *might* be the result of autophagy, i.e. your neurons clean the Nfl, instead of the classical conclusion of neurons destruction. Which means le Nfl level should eventually settle back to normal... which has never been observed with LDR.

- High-dose rapamycin used for immuno-suppression has proven to not be toxic to neurons over years, nor to elevate the Nfl levels either. And contrary to higher doses, LDR stimulates your neurons and may activate something fishy that could mean the elevated Nfl are indeed the result of brain damage.

The ongoing trials about LDR never measure the Nfl, which is bad as this might be the indication of a ticking bomb for the millions who may want to try it.

I do have some positive changes and am hopeful there wil be more. That’s why I try to start this Reddit. (One is no more medication, only for shortcomings based on blood tests). Now I have slept normal for almost a week in five years of lc. Feeling so much more energy is coming back. My head feels on the one site much better but still problems with long and short memory. But at the same time I’m feel like I’m myself again, how I was five years ago. But the hardest part now is so weird: I have absolutely no condition. Can’t walk far. Dit better with medication but it’s time to try and test what I’m capable of and what I can handle. I’m so curios if anyone can relate to my short explanation.

Anyone’s genetic study fire serum amyloid variant? Mine just did… my LC clinic was wondering if I have micro clots well after this finding I guess it’s time to start down this path.. it’s wild!?!

If you've been on social media this week, you may have heard that Invivyd released the topline results of their LIBERTY clinical trial for their new updated monoclonal, VYD2311.

In this post, we're going to dive a bit deeper into what that means, and the path towards this treatment becoming available to the public.

What is VYD2311?

VYD2311 is a monoclonal antibody that's meant to act as prophylactic protection against COVID-19. It's meant as an update to the company's currently authorized monoclonal, Pemgarda.

As the SARS-CoV-2 virus evolves, the monoclonal antibodies which once worked can lose their effectiveness, so it becomes necessary to create updated monoclonals (and antivirals too, for that matter).

Pemgarda and VYD2311 are both based off of the same "parent" monoclonal antibody, adentrivimab, which was the first one the company originally developed. This is common in monoclonal antibody development - rather than start over from scratch with a completely redesigned antibody, researchers can simply update a part of the molecule to better interact with its target - in this case, the SARS-CoV-2 spike protein.

So VYD2311 is essentially the latest monoclonal in this chain, building off of the safety data that's previously been established.

Nonetheless, the FDA does require the company to prove both safety and efficacy before bringing a new monoclonal to market, and that was the topic of this call.

As CEO Mark Elia described in this webinar, Inviviyd is ultimately running two clinical trials of VYD2311.

LIBERTY, the trial which is just now finishing, is comparing the safety and immunogenicity of VYD2311 compared to mRNA vaccine, and also measuring what happens when patients receive it and an mRNA vaccine.

Topline results show VYD2311 had fewer adverse events than the mRNA vaccine (56.5% vs 91.4%) and boosted neutralizing antibody titres 2.5x.

Meanwhile, DECLARATION, which is not yet completed, will be measuring exactly how effective VYD2311 is at preventing COVID-19 infection, compared to placebo. Interestingly, they'll be measuring what happens both when participants receive just one dose, and also what happens when participants receive 3 monthly injections. Ultimately they plan to enroll a total of 1170 adults.

So although we don't yet have evidence of VYD2311's efficacy, Invivyd reports that the topline results from LIBERTY to demonstrate that it is safe and has an acceptable adverse event profile, relative to the mRNA vaccine.

Anti-interference

They also did a really interesting experiment to ensure that VYD2311 administration would not somehow reduce patients' ability to form a response to the vaccine.

It's called the anti-interference experiment, and they show it beginning at the 15:00 mark.

Essentially, for the patient group who received VYD2311 and an mRNA vaccine, they later on took blood samples with a specific technology designed to remove VYD2311 from the blood. Once VYD2311 was removed, they actually showed that these patients had nearly identical levels of anti-spike antibodies to the patients who'd received mRNA alone - a really interesting and important finding.

Based on the evidence so far, Invivyd is anticipating favorable results from DECLARATION.

They can see that this product dramatically raises antiviral titres within the blood.

What happens next?

In their press release, Invivyd explains that they've been in regular contact with the FDA in regards to bringing VYD2311 to market. They plan begin applying for a Biologics License Application (BLA) under the Accelerated Approval Track, using safety and immunogenicity data from both the LIBERTY and the DECLARATION trial.

As the DECLARATION trial is still ongoing, they will keep the final results blinded until the study is complete.

The company explains, "Invivyd believes that as an evidence base, data from LIBERTY, and the upcoming safety and neutralizing titers DECLARATION data on VYD2311, if positive, combined with data from previous Invivyd randomized, placebo-controlled trials EVADE (adintrevimab) and CANOPY (pemivibart) compare favorably to the evidentiary basis routinely used to approve updated COVID vaccines, which also change compositionally to a similar extent as Invivyd monoclonal antibodies."

In other words, they believe the above data alone would complete an evidence base that's equally substantive to the evidence used to grant approval to the mRNA vaccines.

That said, we eagerly await the results of the DECLARATION trial as well!

It would be a real game-changer to have a prophylactic monoclonal antibody on the market with full FDA approval, rather than an EUA.

A note: Invivyd is also planning to study VYD2311 as a treatment for Long COVID and vaccine injury, alongside the SPEAR Study Group.

Announcement here.

We know it's hard sometimes to hang on to hope - but there is work being done, both in terms of better COVID protection as well as Long COVID treatments!

Hang in there everyone!

Links:

LIBERTY press release: https://investors.invivyd.com/news-releases/news-release-details/invivyd-announces-positive-topline-results-liberty-phase-3-study

DECLARATION press release: https://investors.invivyd.com/news-releases/news-release-details/invivyd-announces-initiation-declaration-clinical-trial-phase-3

LONG COVID STUDY ANNOUNCEMENT: https://investors.invivyd.com/news-releases/news-release-details/invivyd-and-spear-study-group-announce-plan-phase-2-study