VEDS Clinical Trial - Enzastaurin

October 13, 2022

We are disappointed to share the news that Aytu Biopharma have today announced they are suspending indefinitely all research and development, including the PREVEnt AR101/enzastaurin clinical trial for vascular EDS.

The reason for suspending research and development is financial and a strategic shift to focus on commercial operations. Like many pharmaceutical companies, Aytu relies on investors to help fund the costs of running a clinical trial. It is during these uncertain times with the global economy, many industries including biotech have been affected.

While this news is deeply upsetting to us all, we as your patient advocacy organisation in the UK are committed to advancing research and treatments into vascular EDS working with vEDS organisations in the US including The VEDS Movement.

As a rare disease community, we have come a long way in recent years with research studies and this will continue. We are in a very strong position to attract further research and clinical trials in the future. Whilst I understand this is a setback, we will continue ‘our challenge to find your cure’.

We are extremely grateful to Aytu for their commitment and hard work and we thank them for the open and transparent working relationship between Annabelle’s Challenge and Aytu team.

We will continue to work with Aytu to investigate any possibility of continuing this trial in the future.  

In the meantime, if you need support or have any questions, please reach out to us via email info@annabelleschallenge.org or call us on 0800 917 8495.

Jared Griffin

Founder & CEO

Annabelle’s Challenge

Following a corporate review, Aytu BioPharma is indefinitely suspending clinical development and removing expenses related to AR101/enzastaurin, Healight, and NT0502, and focusing on revenue growth and near-term cash flow generation.

Aytu BioPharma, today announced a shift of the Company's strategy aimed at accelerating the growth of its commercial business and achieving profitability. As a result, the Company is announcing the indefinite suspension of its clinical development programs, including AR101/enzastaurin for the treatment of Vascular Ehlers-Danlos Syndrome (VEDS). The suspension is expected to save the Company over $20 million in projected future study costs and enable the Company to achieve quarterly positive Adjusted EBITDA in the first half of calendar 2023.

The Company's commercial operations include its prescription and consumer health segments which generated net revenue of $96.7 million in the most recent fiscal year. Excluding R&D expenses related to its now suspended pipeline, the Company had a slightly negative Adjusted EBITDA of $(961,000) from its commercial operations during the quarter ending June 30, 2022, which included the first ever profitable quarter for the Company's prescription segment.

Josh Disbrow, Chief Executive Officer of Aytu BioPharma, commented "This strategic realignment enables us to dedicate our resources to growing our prescription and consumer health segments. Coupled with the suspension of clinical development activities and continued execution against our previously planned $15 million cost cutting program, this shift enables the Company to achieve near-term positive Adjusted EBITDA. In today's economic environment, we believe strongly it is in the best interest of all stakeholders for us to focus our efforts on accelerating the growth of the commercial businesses and generating positive cash flow."

Disbrow added, "We understand that the suspension of our AR101 clinical development program is a disappointment to the VEDS community. We did not take this pause of our clinical development efforts lightly and intend to revisit the program at the appropriate time with the expectation of funding all future clinical development with internally generated cash flow or through partnering."

Prevention of Rupture with Enzastaurin in Vascular Ehlers-Danlos Syndrome.

Aytu BioPharma, Inc. will be sponsoring an upcoming clinical trial to evaluate the effectiveness of AR101 (enzastaurin) in preventing cardiac or arterial events in patients with vascular EDS.

Objective

To evaluate the effectiveness of AR101 (enzastaurin) in preventing cardiac or arterial events in patients with vascular Ehlers-Danlos Syndrome (VEDS) confirmed with COL3A1 gene mutations, compared to placebo.

About AR101 (Enzastaurin)

Enzastaurin is a well characterized PKCβ inhibitor that has been evaluated in over 50 clinical trials, with more than 3,300 patients. This includes a Phase 3 study of nearly 500 patients with 3 years of enzastaurin treatment.

Mutations in the COL3A1 gene have been linked to the loss of structural integrity of the extracellular matrix and increased clinical presentation of vEDS related symptoms, including arterial dissection and/or rupture.

Recent findings from animal studies, in a vEDS mouse model, with similar COL3A1 mutations have shown that the mutation is a key mediator in increased PKC/ERK pathway signaling.

Additionally, in this model, treatment with an inhibitor of PKCβ significantly prevented death due to spontaneous aortic rupture.

Further investigation will be necessary to determine the potential of PKC inhibition as a treatment option.

The trial will investigate the ability of enzastaurin to reduce the severe complications of vEDS. 

You may qualify to participate in the PREVEnt Trial

What is Inclusion/Exclusion criteria?

Researchers follow clinical trial guidelines when deciding who can participate in a study. These guidelines are called Inclusion/Exclusion Criteria. Factors that allow you to take part in a clinical trial are called “inclusion criteria.” Those that exclude or prevent participation are “exclusion criteria.” These criteria are based on factors such as age, gender, the type and stage of a disease, treatment history, and other medical conditions. Before joining a clinical trial, you must provide information that allows the research team to determine whether or not you can take part in the study safely.

Some research studies seek participants with illnesses or conditions to be studied in the clinical trial, while others need healthy volunteers. Inclusion and exclusion criteria are not used to reject people personally. Instead, the criteria are used to identify appropriate participants and keep them safe, and to help ensure that researchers find new information they need.

PREVEnt Clinical Trial Criteria

In the PREVEnt Clinical Trial, there are specific Inclusion & Exclusion criteria. Clinical trial participants will be allowed to continue with their current therapies while enrolled in the study. Below is an overview of some of the key criteria (not fully comprehensive):

Inclusion Criteria:

1. Subjects aged 12 – 60 years old at time of initial screening.
2. Adolescent subjects aged 12 – 17 years old, may be considered to enroll later in the clinical trial pending interim analysis.
3. Diagnosis for VEDS (vascular Ehlers Danlos Syndrome), with a confirmed and documented COL3A1 genetic variant.
4. Subject should be stable, having no VEDS-related vascular events within the past 3 months prior to enrollment.
5. Confirmed use of contraception for both male and female participants.

Exclusion Criteria:

1. Inability to swallow or receive intact tablets.
2. Currently being treated with CYP3A4 inhibitors/inducers within 4 weeks prior to enrollment.
3. Known allergy or hypersensitivity to enzastaurin.
4. Patient currently pregnant or breast feeding.

Other criteria will be reviewed at the first study visit to determine if you are able to participate in the study.

The PREVEnt Trial lasts up to 30 months and requires about 14 visits to a local study clinic (we have sites worldwide) for study-related tests and procedures. Participants will also be invited to participate in an Open Label Extension (OLE) if they would like.