Israel’s Protalix is racing the clock to develop PRX-105, a drug which promises protection against both nerve agents and organic phosphorous compounds used in the pest control industry.
Killing within minutes of exposure, nerve gas is considered one of the most toxic chemical agents known to man. First developed in pre-World War II Germany, nerve gas and nerve agents are still considered a major military threat to homeland security in the United States. Now, a safeguard may be at hand with PRX-105, a novel compound being developed in Israel that offers protection against both nerve agents and the organic phosphorous compounds used in the pest control industry.
Protalix Biotherapeutics, the Israeli company developing the new drug, has just reported completion of the first phase of clinical trials on humans with PRX-105. The company’s technology is based on a plant-based bioreactor which gives the firm the potential to produce a number of drugs, also including treatments for rare illnesses like Gaucher and Fabry disease.
While the only known military use of nerve agents occurred in the Iran-Iraq conflict from the early 1980s to 1988, intelligence authorities have identified many countries with the technical abilities to prepare them for use. Easily dispersed by planes, in missiles or as a spray, frontline national security intelligence suggests that nerve agents could be used in attacks against American citizens.
One of the most widely known incidents of nerve agent use against civilians was the 1995 terrorist attack in the Tokyo subway system, where the Japanese religious group Aum Shinrikyo released the nerve agent sarin, killing 13 people and seriously harming about 50 more.
Nerve agents act through the skin, lungs or eyes, where the phosphorus-containing organic chemicals (organophosphates) disrupt the mechanism through which nerves transfer messages to the body’s organs, causing asphyxiation as those exposed lose control over their respiratory muscles.
Fighting the WMDs
As part of the war against terror, the US Department of Defense is now working to find an antidote to nerve agents, classified as a weapon of mass destruction.
Dr. David Aviezer, Protalix president and CEO, tells ISRAEL21c that “nerve gas is a threat in the eyes of defense authorities. That’s why [in Israel] we all have gas masks. The potential threat is a concern worldwide and the defense authorities of the world are preparing a means to be able to be protected against the threat,” he tells ISRAEL21c.
“The specific guidelines from the FDA [US Food and Drug Administration] could be relatively faster than the normal amount [of time], but I am not able to say,” Aviezer replies, when asked how long it could take before the drug is ready for market.
Working under the tightly regulated terms of the FDA, Aviezer expects that regulatory procedures will be sped up to ensure that if PRX-105 does offer effective protection against nerve agents, it could go through the regulatory channels at a faster rate than usual. The drug is currently filed under an Exploratory Investigational New Drug (IND) application.
And given the nature of the biodefense indications under which Protalix is developing the PRX-105, trials of PRX-105 in humans (Phase II and Phase III) will not be required.
Media sources report that Protalix’s anti-nerve gas drug could be ready as early as next year, and that sales will be contingent on a commitment on the part of the US military to purchase a drug that can counter chemical weapons.
Targeting rare diseases
Developed through the genetic engineering of carrot cells, PRX-105 is an enzyme which is based on a molecule licensed to Protalix by Yissum, the technology transfer arm of the Hebrew University of Jerusalem. It was first developed by Prof. Hermona Soreq, the dean of the university’s math and natural sciences department, and by Yissum’s commercial counterpart at Cornell University in the US.
In addition to its anti-nerve agent drug, the company is ready to launch Uplyso, a therapeutic protein-based drug for treating Gaucher disease, a genetic illness that causes fatty materials to collect in the liver and spleen. About one percent of the total population in the US carries the disease, while among Ashkenazi Jews carriers can number as many as 10% of the population.
Analysts say the drug, found to reduce liver and spleen volume in sufferers, will compete in a market worth $1.25 billion in sales. This month, Protalix obtained a launch date of February 25, 2011 for the drug, which has orphan drug designation, from the FDA.
Protalix is also developing a drug called PRX-102, a therapeutic enzyme for treating Fabry disease, a rare genetic disorder which causes fat build-up in the cells of the kidneys, heart and other organs, affecting about 8,000 people around the world.
Working with Pfizer and the US military
Founded in 1993, with a staff of 200, Protalix is headquartered in northern Israel in Carmiel. Investors in the company include Dr. Philip Frost and the Pontifax venture capital fund. The company is listed on the New York Stock Exchange, and share prices increased following the announcement of positive results of the PRX-105 trial.
Aviezer says Protalix is now working under a partnership agreement with drug giant Pfizer to distribute the Gaucher drug worldwide (but not in Israel). “We are preparing approval to be able to launch production and distribution,” Aviezer tells ISRAEL21c, noting that manufacturing will be located at the company’s Carmiel facility.
Protalix reports that the focus of the first stage of the clinical trials was to test how PRX-105 passes through the human bloodstream, how it’s absorbed by the body’s organs and how it breaks down and exits the body. The company notes that the drug did not cause adverse side effects.
Having established that the compound is non-toxic in humans, the company plans to test the protective effects of PRX-105 on large species of animals such as monkeys, which have been exposed to nerve gas. They will also gauge dosage versus protection levels.
While for obvious ethical reasons the company will not expose humans to nerve gas to test the compound’s protective effects, Protalix did report that PRX-105 had preventative effects after exposure to organic phosphorus, which is used in the pesticide industry.
The US military has reportedly issued a tender to purchase 350,000 units of a drug that can counter chemical weapons. Such a deal would be worth hundreds of millions of dollars. Protalix reports that the company is in discussions with both civil and military agencies in the US and Israel with respect to the development of PRX-105, which will hopefully succeed in doing just that.