RiVax® to Prevent Ricin Poisoning
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Orphan and/or Fast Track Designation
A World Leading Ricin Toxin Vaccine Candidate
Ricin toxin is a lethal, yet easily manufactured, white powder which can induce irreversible symptoms within four hours of exposure and may cause death within 48-72 hours. RiVax® is a safe alum-adjuvanted subunit vaccine candidate which may prevent death and injury from any route of exposure to ricin toxin. Intended for use with emergency first responders and warfighters that may unexpectedly encounter ricin toxin, RiVax® is a thermostabilized vaccine candidate which can be stored at room temperature for extended periods, compatible with United States government stockpiling requirements.
Background on Ricin Toxin
Ricin toxin causes cell death once it penetrates the cell membrane. Ricin toxin can penetrate cells within 4 hours of exposure. Depending on the route of exposure (ingestion, inhalation or injection), ricin toxin has different initial symptoms. Regardless of initial route of exposure, ricin poisoning results in death with sufficient exposure.
Ricin is easily isolated from mash from local grown castor beans or generated in the production of castor oil. Approximately 1 M metric tons of castor oil are produced annually.
Current Ricin Poisoning Treatments
There are NO FDA-approved prophylactic or post-exposure therapies for ricin toxin exposure.
Investigational therapies for ricin intoxication are generally limited for use within four hours of ricin poisoning. Because poisoning events are often of unknown origin (i.e., the identity of the “white powder” is initially unknown), a four hour time limit is extremely problematic.
Our Approach: RiVax®
Because of the rapid internalization of ricin toxin, vaccination is the best strategy for dealing with ricin intoxication. Antibodies generated in response to vaccination are continuously present and can “mop up” ricin as soon as it is present.
The RiVax® vaccine candidate uses one of the safest vaccination approaches known – using a modified inactivated protein component of the ricin toxin itself to raise antibody responses, combined with an alum adjuvant to boost the body’s response to the vaccine.
RiVax® also uses Soligenix’s proprietary ThermoVax® technology to create a vaccine which is stable for long term storage even at very high temperatures (e.g., 40°C or 104°F). This means the RiVax® protein may be stored for long periods of time allowing it to be stockpiled for future use.
What is RiVax®?
RiVax® primarily consists of two components:
1. A modified form of the A-chain of the ricin toxin. The modifications have removed the biological activity of the protein while still retaining its shape to trigger an effective antibody response.
2. Aluminum (“alum”) as an adjuvant. Alum is a very well-known adjuvant, used in many commercial vaccines, with well-known safety profiles.
RiVax® is administered as an intramuscular injection on 2 or 3 occasions, resulting in the adaptive immune system mounting an antibody response.
Mechanism of Action
RiVax® induces the adaptive immune system to produce antibodies that recognize and bind ricin toxin, preventing it from getting inside cells and killing them. After intramuscular injection with RiVax®, IgG and other antibodies are produced and circulate within the body and are able to mop up ricin whether it was inhaled, eaten or injected.
The initial alum-adjuvanted RiVax® vaccine generated antibodies that degraded very quickly. By using Soligenix’s proprietary technology, ThermoVax®, a thermostabilized version of RiVax® was produced so it can be stored for long periods of time (i.e., 12 months) even at elevated temperatures (e.g., 40°C or 104°F).
The thermostabilized version of RiVax® is produced by lyophilizing (freeze-drying) the vaccine in individual vials to form a solid white cake. This removes water and other components from the material which would otherwise destabilize the protein. By using a proprietary process, the protein-aluminum combination remains intact.
The solid, lyophilized material can then be returned to a liquid form immediately before use by simply adding sterile water and mixing prior to injection. Because sterile water is also very common and very stable, this results in an extremely convenient product that can be stored for extended periods. Long term storage and ease of use are key attributes for a product that may be stockpiled.
This same thermostabilization process has been demonstrated to be compatible with other subunit protein vaccines.
Clinical Studies & Commercialization for RiVax
Soligenix will be pursuing approval for RiVax under the Animal Rule. Work to date has focused on improving manufacturing processes and identifying correlates of immune protection that can demonstrate that protection observed in animals is likely to translate to humans. The RiVax antigen has been shown to be safe in 2 Phase 1 studies in humans. Future steps will include pivotal animal efficacy studies (to demonstrate potency in animals), and Phase 2 clinical study in humans (to confirm safety and correlate immune markers of protection with outcomes from animal studies).
Further information on the RiVax® program can be found in this interview with Dr. Richard Straube.
Interested in partnering with us for commercializing in specific geographical regions?
Previous Nonclinical Studies with RiVax®
Previous studies with RiVax® have demonstrated up to 100% protection to subsequent ricin poisoning, even if the ricin is introduced by inhalation, the most lethal route of administration. The protected animals also had no signs of gross lung damage, a serious and enduring ramification with long-term consequences for survivors of ricin poisoning.
Previous Clinical Studies with RiVax® protein
RiVax® protein has demonstrated safety in two Phase 1 clinical studies:
- An open label, ascending dose Phase 1 trial of un-adsorbed RiVax® protein (no alum) vaccine using three doses of up to 100 µg of protein was well tolerated and generated both total and neutralizing antibody responses.
- An open label, ascending dose Phase 1 trial of alum-adsorbed RiVax®protein vaccine in a liquid formulation using three doses of up to 100 µg of protein was well tolerated and generated higher and longer lasting total and neutralizing antibody responses.
RiVax® has Fast Track designation for the prevention of ricin intoxication by the US FDA.
RiVax® has been granted Orphan Drug designation for the prevention of ricin intoxication by the US FDA and by the European Medicines Agency (EMA).
As a new chemical entity, an FDA approved RiVax® vaccine has the potential to qualify for a biodefense Priority Review Voucher (PRV), which allows the holder to qualify for accelerated review by the FDA, potentially enabling a blockbuster drug to come on the market sooner and have a longer lifetime before patent expiry. PRVs are transferable and can be sold, with sale values in excess of $100 million recorded to date.
What is the Animal Rule?
Because ricin intoxication is an unpredictable event and because exposing humans with ricin is unethical, approval of a ricin toxin vaccine will utilize the FDA “Animal Rule” (21 CFR 601.90 through 601.95).
The Animal Rule represents a different regulatory pathway from normal clinical development. Whereas normal clinical development depends on clinical trials – including safety (Phase 1), proof of concept efficacy and safety (Phase 2) and definitive efficacy and safety (Phase 3) trials, the Animal Rule instead utilizes a combination of human and animal testing. There are 3 key components to using the Animal Rule.
- Safety is demonstrated in humans (Phase 1 and Phase 2 studies)
- Efficacy is demonstrated in animals in pivotal animal studies (replacing the traditional Phase 3 studies)
- Both the response to disease and the response to treatment must be demonstrated to be similar between the animal models and humans
This additional requirement for increased agreement between animal and human disease and treatment response is unique to the Animal Rule and is an area Soligenix has made significant progress on, identifying correlates of immune response that are applicable across different species.
Soligenix has a strong worldwide intellectual property position on the composition of matter of RiVax®, the unique thermostabilized formulation for RiVax® and the combination of RiVax® with other subunit vaccines in a single vaccine.
Orphan Drug designation also confers 7 years market exclusivity in the US and 10 years in Europe, if approved.