What is Viprinex™ (ancrod)?
Viprinex™ (ancrod), a novel Fibrinogen Reducing Agent (FRA), is an enzyme that reduces levels of fibrinogen, the primary protein involved in blood clotting. Reducing fibrinogen in the blood also reduces blood viscosity, which may improve blood flow. Additionally, as the fibrinogen is broken down, natural mechanisms are activated to dissolve preformed blood clots. Since Viprinex acts in the blood for a longer period, its effect on brain blood flow should be sustained longer than with existing therapy.
The Viprinex Phase 3 trials, currently enrolling worldwide, are investigating whether Viprinex can safely and effectively reduce disability following an acute ischemic stroke.
Prior studies suggest Viprinex may be safe and effective when treatment starts as late as six hours from the onset of stroke symptoms, enabling more ischemic stroke patients to be treated than with currently approved therapy.
How does Viprinex work?
Stroke occurs when a blood clot blocks blood flow to critical areas of the brain. Viprinex is thought to work in three ways to improve blood flow to areas of the brain affected by the stroke:
- It interferes with fibrinogen’s ability to participate in blood clot formation, which should limit clot growth and reduce the chance of reocclusion due to new clot formation.
- It reduces blood viscosity (resistance to flow), which should improve blood flow to areas of the brain affected by the stroke.
- It indirectly activates the natural blood clot dissolving mechanism, which should further help restore blood flow to areas of the brain affected by the stroke.
Why would a drug targeting fibrinogen be effective in patients with acute ischemic stroke?
Elevated fibrinogen levels are a risk factor for stroke and may be associated with greater stroke disability. Although the specific mechanism(s) leading to improved outcome by reducing fibrinogen levels in patients with acute stroke has not been proven, prior studies with Viprinex that target fibrinogen have shown a benefit from this approach.
Would Viprinex work only for patients with high fibrinogen levels?
No. In prior stroke studies with Viprinex, the rate at which fibrinogen was reduced was more closely associated with better outcome than was the patient’s initial fibrinogen level. Therefore, Viprinex should be effective regardless of the initial fibrinogen level.
Why is Viprinex needed?
With more than 700,000 patients experiencing stroke each year and existing drug therapies limited to use only during the first three hours after stroke onset, there is a substantial unmet medical need to increase the available treatment options for stroke patients. Because the symptoms of stroke are not often recognized quickly, a substantial number of patients do not seek treatment until after the three-hour treatment window is closed. Even within the three-hour window, concerns about bleeding risk further limit the number of patients who receive stroke treatment.
How is Viprinex derived and made available for the trials?
Viprinex is an enzyme derived from the venom of the Malayan pit viper. The enzyme is highly specific for fibrinogen. The snakes are milked for the raw venom and the actual enzyme, ancrod, is purified from the venom.
The snakes are bred in a sterile, high-humidity GMP (good manufacturing practice) facility in Germany. NTI has a sufficient inventory of venom to complete the Phase 3 trials and initial market launch if Viprinex is approved. The existing colony of snakes and their offspring will provide additional venom to support the market after commercialization.
What is the history of Viprinex in the treatment of stroke?
Earlier Viprinex trials used a dosing regimen that infused the drug over five to seven days, which kept fibrinogen levels low for too long. NTI has changed the treatment paradigm to a three-hour intravenous high dose drip designed to reduce fibrinogen levels quickly while avoiding prolonged low fibrinogen levels. Stopping the infusion after three hours permits fibrinogen to return to normal within a few days and should reduce bleeding risk.
- Viprinex treatment studies of acute ischemic stroke, including two prior Phase 3 trials, involved more than 1900 patients from around the world. Of the two Phase 3 trials, one demonstrated efficacy, the other was neutral. (Additional data is available on request.)
- Findings from an NTI-sponsored retrospective analysis indicated that improved safety and efficacy may be achieved with a modified dosing regimen consisting of a brief Viprinex infusion with no maintenance dosing.
- Based on the retrospective analysis of the prior clinical studies, this new dosing regimen of Viprinex is currently being evaluated in two ongoing international Phase 3 pivotal trials.
What is the Viprinex clinical program?
Viprinex is being investigated in two Phase 3 trials. NTI plans to enroll 1300 acute ischemic stroke patients into two randomized, double-blind, placebo-controlled studies. These studies are designed to investigate whether Viprinex can safely and effectively reduce stroke disability compared to placebo following an acute ischemic stroke.
If the two pivotal Phase 3 clinical trials (called the Ancrod Stroke Program I and II) are positive, they will be submitted to regulatory authorities as part of a marketing application. The primary endpoint for both trials is the modified Rankin Scale, a measure of independent day-to-day function at 90 days post stroke. Secondary endpoints include the NIH Stroke Scale score and the Barthel Index. Important safety variables include symptomatic intracranial hemorrhage and mortality.
How does Viprinex differ from rt-PA?
Prior studies suggest Viprinex might be safe and effective when treatment starts as late as six hours from the onset of stroke symptoms, enabling more ischemic stroke patients to be treated. rt-PA is approved for use within three hours from the onset of stroke symptoms. Since Viprinex acts in the blood for a longer period, its effect on brain blood flow should be sustained longer than with existing therapy.
What’s most important is that there is a substantial need to increase treatment options that are safe and effective for stroke patients.
How does Viprinex differ from mechanical devices?
Viprinex is given as an intravenous injection, which means it can be made available to a broader population without the need to live near major medical centers that specialize in invasive interventions. Mechanical devices also carry their own risks of bleeding and post-procedural blood clot formation.
What’s most important is that there is a substantial need to increase treatment options that are safe and effective for stroke patients.
What is NTI?
Neurobiological Technologies, Inc, (NASDAQ: NTII) is a biopharmaceutical company focused on developing novel, first-in-class agents for central nervous system conditions and other serious unmet medical needs. The Company’s most advanced product candidate in Phase 3 clinical testing is Viprinex™ (ancrod). The Company’s pipeline includes other drug candidates in early-stage development, including a first-of-its-kind drug for the treatment of Alzheimer's disease. |
