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  • Cardiovascular disease is the leading cause of death globally, according to the World Health Organization (WHO).
  • As a result, millions of patients around the world are treated with anticoagulants in the hope of preventing life threatening cardiovascular events such as strokes, pulmonary embolisms, and heart attacks.
  • Anticoagulants used in clinical practice include warfarin, heparin, and direct oral anticoagulants (DOACs), such as thrombin and factor Xa inhibitors. However, there may be a higher risk of bleeding in some patients receiving DOACs.
  • Verseon, a company based in California, has developed a next-generation oral anticoagulant that has the potential to prevent unwanted clots while preserving the body’s ability to stop excessive bleeding.

The primary function of anticoagulants is to prevent blood clots from forming. These medications interfere with blood factors; the proteins responsible for the coagulation, or thickening, process.

There are several blood factors and different anticoagulants target different factors.

Unfortunately, anticoagulant medications do cause side effects that may lead to serious complications, such as excessive bleeding.

To address this problem, Verseon, a company based in California, has developed several novel drug candidates for cardiovascular disease. In their new research, published in the European Journal of Medicinal Chemistry, the research team describes compounds from a novel class called N-acylpyrazoles.

Their products have been termed “Precision Oral Anticoagulants” (PROACs) and according to Verseon, they have “optimized various physicochemical properties — including potency, selectivity, and in vivo stability.”

“Verseon has developed precision oral anticoagulants (PROACs) that can prevent potentially life threatening blood clots without increasing the risk of bleeding,” Dr. David Kita, Ph.D., Chief Scientific Officer at Verseon, told Medical News Today.

“Hundreds of millions of cardiovascular disease patients worldwide need such anticoagulants urgently,” Dr. Kita said.

“The medicinal chemists at Verseon optimized the various properties of the drug candidates to make them more potent, stable, and selective. While potency of a drug is key to its action on the disease, stability makes it possible to administer the drug with fewer daily doses. Enhancing the selectivity of a drug is important in avoiding adverse side effects.”

– Dr. Kita

“Verseon’s drug belongs to a novel class of drug molecules that act by a different mechanism on its target in the body. This mechanism preserves hemostasis and is key to the lower bleeding risk demonstrated in ‘in vivo’ tests,” Dr. Kita explained.

The researchers note that PROACs do not inhibit platelet function which could explain the lower bleeding risk that may be associated with these drug candidates. The company highlights that these properties make them good candidates for future anticoagulant therapies.

The thrombin inhibitors described in this paper are effective at preventing clots in animal models. In addition, they do not inhibit the thrombin-mediated activation of platelets. This is a critical step to stop injury-induced bleeding, meaning these drug candidates have shown far lower bleeding risks in animal models.

Although these products need to be fully tested in human clinical trials, Dr. Kita highlighted their potential future applications.

“Patients with a heart condition called non-valvular atrial fibrillation, a very common form of [arrhythmia], are at risk of suffering strokes. Currently marketed anticoagulants carry high bleeding risk. Verseon’s PROAC drug candidates, with their novel pharmacology, can potently reduce the risk of strokes without elevating bleeding risk,” Dr. Kita said.

“Another very large patient population who suffer from acute coronary syndrome can benefit from lifelong simultaneous administration of antiplatelet drugs and anticoagulants. Unfortunately, such dual therapy with currently marketed anticoagulants carries an unacceptable amount of bleeding risk,” he said.

“Verseon’s PROACs, with their unique mechanism of action, aim to offer a safe option for long-term dual therapy with antiplatelets. Over 51 million patients in high-income countries would benefit from safe long-term anticoagulant-antiplatelet dual therapy,” he added.

Dr. Jayne Morgan, a cardiologist at the Piedmont Hospital/Healthcare, not involved in this research, highlighted the challenges that patients experience when receiving anticoagulation therapies:

“Errors could lead to hemorrhage on one end, or thrombosis on the other. Bleeding is the major concern including rare complications such as intracranial hemorrhage, or large GI bleeds.”

Dr. Mark Goldin, director of clinical trials at the Feinstein Institutes for Medical Research, also not part of this study, agreed and told MNT that “when doctors prescribe anticoagulants, they must always balance the need for treatment with the risks of bleeding that can occur.”

“The anticoagulants in this pre-clinical study are promising as they may have even lower bleeding risk than standard treatments, such as factor Xa inhibitors (like Xarelto and Eliquis), which already have excellent safety profiles and do not typically require blood test monitoring,” Dr. Goldin explained.

Mellanie True Hills, founder & CEO of the American Foundation for Women’s Health and StopAfib.org, said that “patients who receive anticoagulants have to balance the risk of bleeding with the risk of stroke.”

“Patients currently on anticoagulants must be careful with their daily activities, such as using household knives in the kitchen, cutting tools for yard work, and participating in dangerous sports and hobbies that can result in bleeding injuries,” she explained. “Some people on anticoagulants have so much bruising from them that they have to cover up their torso and extremities due to embarrassment over the bruising.”

Although this new research is promising, Dr. Goldin urged caution:

“It is important to be very cautious in interpreting this early data, as these drugs have yet to be studied in humans and will need to demonstrate efficacy and safety in large clinical trials.”

Hills advocates for patients receiving anticoagulant therapy. She said the novel anticoagulants “appear to have the best of both worlds,” potentially making it possible to prevent strokes without the downside of bleeding issues.

“The fear of strokes and bleeds takes a mental and emotional toll on afib patients. This added stress worsens afib and increases the toll afib takes on patients. Thus, being able to live their lives without these issues would significantly improve their quality of life in so many ways,” Hills added.

When asked how soon this new class of anticoagulant could be approved for use in patients, Dr. Kita said:

“The first drug candidate in our program is currently undergoing phase I clinical trials. Our second candidate is about to enter clinical trials. We expect our drug candidates to gain approval in the next 3 to 4 years.”