PREVEnt Trial: Prevention of Rupture with Enzastaurin in Vascular Ehlers-Danlos Syndrome
The Background: New Research at Johns Hopkins and a Biopharma Company in vEDS
In 2019, we started learning about new research at Johns Hopkins when Dr. Dietz and his team began sharing early findings from a study that provided the foundation for this upcoming trial.
There was tremendous excitement from the patient community at the time; however, it was still early. The Johns Hopkins research was conducted in mice and, as we know, we need to understand a treatment’s effectiveness in humans before declaring how well it works.
The same year, Rumpus Therapeutics - a biopharmaceutical company focused on the treatment of pediatric onset rare and orphan diseases - began working on a vEDS clinical trial. The company looked to utilize the research from Johns Hopkins to run a clinical trial on a drug called enzastaurin. If the trial is successful in vEDS patients, enzastaurin could become the first FDA-approved treatment for vascular Ehlers-Danlos Syndrome.
The Research: From the Lab to a Clinical Trial
In 2020, the Johns Hopkins researchers formally published their findings regarding a new way to prevent arterial rupture in vEDS. The highlights of the study (in less technical terms!) are as follows:
Researchers used mice with vEDS, which very closely mirrored the symptoms shown in humans with vEDS
In mice that had died of vEDS, they noticed something that was consistently abnormal in a particular signaling pathway (in what is known as the PLC/IP3/PKC/ERK signaling pathway)
They gave the mice certain treatments that they believed would inhibit that pathway (i.e., pharmacological inhibitors of ERK1/2 or PKCβ)
They found that treating the mice with enzastaurin reduced the risk of death from aortic dissection, with 80% of enzastaurin-treated vEDS mice surviving after 40 days of treatment compared to only 50% of untreated vEDS mice (see the curve below)
The results were significant and gave Johns Hopkins researchers as well as the team at Rumpus Therapeutics optimism that a similar treatment may work in humans
In April 2021, Rumpus Therapeutics sold the rights to enzastaurin for vEDS to Aytu BioPharma to access funding for the trial (see the press release here). The Rumpus Therapeutics team joined Aytu and began preparing for a clinical trial. In October 2022, Aytu Biopharma announced a suspension of the trial as they work to secure funding.
The Treatment: How can Enzastaurin Help?
Enzastaurin is a small molecule, serine/threonine kinase inhibitor of the PKC beta, PI3K and AKT pathways, which means that it acts on the same pathways that Johns Hopkins researchers discovered were abnormally activated in vEDS mice that had died of the condition.
Using enzastaurin in vEDS is new, however, the drug isn't. It was originally owned by other pharmaceutical companies (e.g., Eli Lilly & Company) who studied it in other conditions. As a result, enzastaurin has been evaluated in over 50 clinical trials, with more than 3,300 patients, including a Phase 3 study of nearly 500 patients with 3 years of enzastaurin treatment.
The clinical trial will require patients to have a confirmed COL3A1 mutation to participate. Note that patients may still get re-tested as a part of the trial but having a genetic confirmation ahead of the trial's enrollment period is important.
If you believe you have vEDS but do not have a positive test result, we suggest you visit your medical provider to get the diagnosis in advance of enrollment so that you'll have the option to participate.
If you can’t access a provider to order the test, FIGHT vEDS provides instructions on how to order a saliva test from home for $375 without insurance:
Trial enrollment is currently suspended; however, subscribe to FIGHT vEDS below to be notified when enrollment restarts.
Caitlin J Bowen, Juan Francisco Calderón Giadrosic, Zachary Burger, Graham Rykiel, Elaine C Davis, Mark R Helmers, Kelly Benke, Elena Gallo MacFarlane, Harry C Dietz. 2020 Feb 3. Targetable cellular signaling events mediate vascular pathology in vascular Ehlers-Danlos syndrome. The Journal of Clinical Investigation. 175C:40-47.