Cadrenal Therapeutics Highlights Presentation of New Trial Data at ISHLT Conference Demonstrating the Importance of Anticoagulation Quality in LVAD Patients

Rhea-AI Summary

Cadrenal Therapeutics (Nasdaq: CVKD) has presented new data from the ARIES-HM3 trial at the ISHLT conference, showing the significant impact of anticoagulation quality in LVAD patients. The trial highlighted the deficiencies of warfarin and introduced tecarfarin, a novel VKA, as a potential replacement. Tecarfarin has received Orphan Drug Designation from the FDA for preventing thromboembolism in patients with mechanical circulatory support devices like LVADs.

The ARIES-HM3 data indicates a direct correlation between lower therapeutic range times (TTR) and higher bleeding events. The average patient experienced a 30% rate of serious bleeding even without aspirin in the regimen. Incremental improvements in TTR corresponded to significant reductions in bleeding rates, emphasizing the potential of tecarfarin to provide more stable anticoagulation compared to warfarin.

The data is under FDA review, and Cadrenal plans to pursue further pivotal trials to validate tecarfarin's effectiveness for LVAD patients.

Positive

• Tecarfarin received Orphan Drug Designation from the FDA.
• Tecarfarin shows potential to improve TTR compared to warfarin.
• ARIES-HM3 trial data highlights tecarfarin's ability to reduce bleeding events in LVAD patients.
• Cadrenal plans to pursue further pivotal trials evaluating tecarfarin.

Negative

• The ARIES-HM3 trial data is still under FDA review.
• Current anticoagulation with warfarin only achieves the target range 56% of the time.
• 30% of patients in the ARIES-HM3 trial experienced serious bleeding events.
• Labeling changes related to the antithrombotic regimen have not been approved by the FDA.

Medical Research Analyst

Cadrenal Therapeutics has presented new trial data at the ISHLT conference that highlights tecarfarin's potential benefits over warfarin for LVAD patients. LVADs are mechanical devices that support heart function and patients with these devices require anticoagulant therapy to prevent blood clots. The current standard, warfarin, shows significant limitations, with a therapeutic range only achieved 56% of the time, leading to a high rate of bleeding events according to the ARIES-HM3 trial.

Tecarfarin could address these limitations by offering more stable anticoagulation, especially important for patients with renal dysfunction or those on multiple medications. The data indicating that each 10% improvement in TTR correlates with a significant reduction in bleeding events is particularly compelling. This positions tecarfarin as a potential game-changer in the management of LVAD patients.

With the FDA's Orphan Drug Designation, tecarfarin benefits from incentives such as extended market exclusivity, which could accelerate its path to commercialization. However, it's important to remain cautious as the FDA has yet to approve any labeling changes regarding the antithrombotic regimen. The pivotal trial that Cadrenal intends to pursue will be critical in determining tecarfarin's future market success.

Financial Analyst

Cadrenal Therapeutics appears to be strategically leveraging tecarfarin's potential market differentiation following its FDA Orphan Drug Designation. This designation not only underscores the unmet medical need but also provides financial benefits including tax credits and market exclusivity.

The potential market for a novel anticoagulant like tecarfarin is significant, especially given the inadequacies of current therapies like warfarin. If tecarfarin can demonstrate superior clinical outcomes, it could capture a substantial market share, particularly in the niche but critical segment of LVAD patients. However, the market-leading DOACs like Eliquis, although not indicated for LVAD patients, present competition that shouldn't be ignored in broader anticoagulation contexts.

Investors should watch for the upcoming pivotal trial and FDA decisions closely. Positive outcomes could drive stock valuation significantly higher. However, the financial risk remains if the trial fails to meet endpoints or the FDA does not approve tecarfarin for clinical use. Given the competitive landscape and the regulatory hurdles, the short-term volatility could be high, but the long-term potential remains promising.

Tecarfarin, which recently received Orphan Drug Designation from the FDA for the prevention of thromboembolism and thrombosis in patients with an implanted mechanical circulatory support device, has the potential to improve the time in therapeutic range a factor correlated in the ARIES-HM3 trial with better patient outcomes

PONTE VEDRA, Fla., June 3, 2024 /PRNewswire/ -- Cadrenal Therapeutics, Inc., (Nasdaq: CVKD), a biopharmaceutical company developing tecarfarin, a late-stage novel oral and reversible anticoagulant (blood thinner) designed to prevent heart attacks, strokes, and deaths due to blood clots in patients with rare cardiovascular conditions, today highlighted a groundbreaking presentation at the International Society for Heart & Lung Transplantation (ISHLT) 44th Annual Meeting & Scientific Sessions.

These new findings from secondary analyses of the ARIES-HM3 trial were released in a presentation titled, "Impact of Vitamin K Antagonist (VKA) Therapy On Outcomes In a Randomized Controlled Trial of Aspirin Removal In Left Ventricular Assist Device (LVAD) Patients - A Pre-Specified Analysis From the Aspirin and Hemocompatibility Events With a Left Ventricular Assist Device in Advanced Heart Failure, or the ARIES-HM3, Randomized Clinical Trial."

The ARIES-HM3 trial data demonstrated that lower time in therapeutic range, or TTR, translated directly to excessive bleeding events. The "average" patient in the ARIES-HM3 study had a 30% rate of serious bleeding events even after aspirin was eliminated as part of the antithrombotic regimen, and persistent bleeding was inversely correlated with TTR.

The ARIES-HM3 clinical study was sponsored by Abbott (NYSE: ABT), which evaluated a new clinical approach to patient management that included removal of aspirin as part of the antithrombotic regimen warfarin. The data is currently under review by the FDA. Labeling changes related to the antithrombotic regimen have not been approved by the FDA at this time.

Dr. Mandeep Mehra, who chaired the ARIES-HM3 study, holds the William Harvey Distinguished Chair in Advanced Cardiovascular Medicine and is Executive Director of the Center for Advanced Heart Disease at Brigham and Women's Hospital, commented, "This comprehensive analysis identifies adequacy of VKA use (as measured by TTR) as a significant risk marker for bleeding events and provides new clinical direction for further mitigation of bleeding to enhance hemocompatibility with the HeartMate 3 LVAD." Mehra continued, "Each incremental improvement of 10% above the median of 56% TTR trends in a significant further reduction in bleeding rate. Tecarfarin could potentially be an important therapy for patients with LVADs who all require chronic anti-coagulation since it does not get affected by drug-drug interactions or changes in kidney function like warfarin and deserves further study."

"The ARIES-HM3 trial data underscores the deficiencies of warfarin and the need for a new VKA therapy for patients with LVADs. We believe our drug candidate, the next-generation VKA tecarfarin, with its unique retrometabolic design that provides for more stable anticoagulation than warfarin, is the much-needed replacement therapy. We intend to pursue a pivotal trial evaluating tecarfarin effectiveness for LVAD patients," said Quang Pham, Founder, Chairman and Chief Executive Officer of Cadrenal Therapeutics. "Cadrenal commends Abbott's commitment to LVAD patients in sponsoring this important trial and analyses."

On April 9, 2024, Cardenal Therapeutics announced that the United States Food and Drug Administration (FDA) had granted tecarfarin Orphan Drug Designation for the prevention of thromboembolism and thrombosis in patients with an implanted mechanical circulatory support device, which includes the left ventricular assist device (LVAD).

The current market-leading direct oral anticoagulants (DOACs), such as Eliquis, are not indicated for patients with LVADs due to a lack of evidence of benefit, while the level of anticoagulation achieved with warfarin was achieved in the target range only 56% of the time in the ARIES-HM3 trial. Patients whose level of anticoagulation was in the therapeutic range > 56% had better outcomes than those with lower levels. This highlights the potential role for investigating new VKA agents in improving clinical outcomes in LVAD patients.

VKA anticoagulation is prescribed for the prevention of LVAD-related clotting. However, the only available VKA is warfarin, which was approved for human use in 1954. Tecarfarin has been shown to improve TTR, particularly in patients taking multiple medications, and be more stable in patients with renal dysfunction which is common in LVAD patients.

ABOUT CADRENAL THERAPEUTICS, INC.
Cadrenal Therapeutics is developing tecarfarin for unmet needs in anticoagulation therapy. Tecarfarin is a late-stage novel oral and reversible anticoagulant (blood thinner) to prevent heart attacks, strokes, and deaths due to blood clots in patients with rare cardiovascular conditions. Tecarfarin has orphan drug and fast-track designations from the FDA for the prevention of systemic thromboembolism (blood clots) of cardiac origin in patients with end-stage kidney disease (ESKD) and atrial fibrillation (AFib) and just received orphan drug designation for the prevention of thrombosis and thromboembolism in patients with ventricular assist devices (VADs). Cadrenal is also pursuing additional regulatory strategies for unmet needs in anticoagulation therapy for patients with thrombotic antiphospholipid syndrome (APS). Tecarfarin is a next-generation Vitamin K Antagonist (VKA) specifically designed to use a different metabolism pathway than the oldest and most commonly prescribed VKA warfarin. Tecarfarin has been evaluated in eleven (11) human clinical trials and more than 1,000 individuals. In Phase 1, Phase 2, and Phase 2/3 clinical trials, tecarfarin has generally been well-tolerated in both healthy adult subjects and patients with chronic kidney disease. For more information, please visit: www.cadrenal.com.  

Safe Harbor Statement
Any statements contained in this press release about future expectations, plans, and prospects, as well as any other statements regarding matters that are not historical facts, may constitute "forward-looking statements." These statements include statements regarding tecarfarin having the potential to improve the time in therapeutic range which analysis of the ARIES-HM3 trial reveals is associated with better patient outcomes. TTRs as predicting increased risk for bleeding events, the VKA tecarfarin, filling the market void for a next-generation VKA, the Company pursuing a pivotal trial evaluating tecarfarin effectiveness for LVAD patients. The words "anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "plan," "potential," "predict," "project," "should," "target," "will," "would" and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including the ability of tecarfarin to improve the time in therapeutic range, the ability of the Company  to advance tecarfarin with patients with left ventricular assist devices (LVADs), thrombotic APS, and those with AFib and ESKD and the other risk factors described in the Company's Annual Report on Form 10-K for the year ended December 31, 2023, and the Company's subsequent filings with the SEC, including subsequent periodic reports on Quarterly Reports on Form 10-Q and Current Reports on Form 8-K. Any forward-looking statements contained in this press release speak only as of the date hereof and, except as required by federal securities laws, the Company specifically disclaims any obligation to update any forward-looking statement, whether as a result of new information, future events, or otherwise.

For more information, please contact:

Cadrenal Therapeutics:
Matthew Szot, CFO
858-337-0766
press@cadrenal.com 

Investors:
Lytham Partners, LLC
Robert Blum, Managing Partner
602-889-9700
CVKD@lythampartners.com 

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SOURCE Cadrenal Therapeutics, Inc.

FAQ

What new data did Cadrenal Therapeutics present at the ISHLT conference?

Cadrenal Therapeutics presented ARIES-HM3 trial data showing the impact of anticoagulation quality in LVAD patients, highlighting the deficiencies of warfarin and the potential of tecarfarin.

What is the significance of tecarfarin receiving Orphan Drug Designation?

Orphan Drug Designation from the FDA indicates tecarfarin's potential for treating rare conditions, specifically preventing thromboembolism in patients with mechanical circulatory support devices.

How does tecarfarin compare to warfarin in terms of therapeutic range?

Tecarfarin has been shown to improve the time in therapeutic range (TTR) compared to warfarin, which could result in fewer bleeding events for LVAD patients.

What are the current limitations of warfarin for LVAD patients?

Warfarin's level of anticoagulation was achieved in the target range only 56% of the time in the ARIES-HM3 trial, leading to a 30% rate of serious bleeding events.

What are Cadrenal Therapeutics' plans following the ARIES-HM3 trial data?

Cadrenal Therapeutics plans to pursue further pivotal trials to evaluate the effectiveness of tecarfarin for LVAD patients.