The discovery of antibiotics nearly a century ago is heralded as one of the great advances in modern medicine. But these wonder drugs have become less effective over time, and tens of thousands of Americans now die every year when physicians run out of ways to ward off deadly infections.
Pharmaceutical companies are now responding, and at least three-dozen new antibiotics are now under development nationwide, experts said. A team of researchers in New Jersey is one of the leaders in this effort, and its work on a novel approach could be ready for patients by 2020.
Based on technology created by Rutgers scientists and developed with help from TAXIS Pharmaceuticals, a drug maker in Monmouth Junction, TXA709 is specifically designed to treat MRSA, an extremely deadly bacterial infection that doesn’t respond to existing antibiotics. The Federal Drug Administration has now given the team approval to test the drug on animals, and they hope to follow with human trials in the spring.
TXA709 was developed by Daniel Pilch, an associate professor in the pharmacology department at Robert Wood Johnson Medical School, and Edmond LaVoie, a professor and chair of the medicinal chemistry department at Rutgers’ pharmacy school, explained Yair Harel, the executive director for New Ventures at Rutgers.
Rutgers holds the license. The school partnered with TAXIS as part of a standard process to continue trials, research, and other aspects of commercialization, Harel said. Pilch and LaVoie helped form the company in 2009.
MRSA, or methicillin-resistant Staphylococcus aureus, kills some 19,000 Americans and adds $3 billion to the country’s annual healthcare costs, according to the Rutgers research team’s announcement last spring. Advocates gathered this past weekend in Chicago to mark World MRSA Day on Sunday, October 2 — an event first designated in 2009.
Their efforts may be having an effect. Infection rates have been declining in recent years nationwide, including in New Jersey. But reports of MRSA at Garden State hospitals were roughly five percent higher than the national average, according to data from the federal Centers for Disease Control and Prevention. While it is not limited to healthcare facilities, most infections show up in hospitals, rehab, or nursing homes among patients who have compromised immune systems.
The underlying problem for MRSA, and other diseases resistant to antibiotics, is that as these life-saving drugs became more common, the ever-evolving bacteria grew in new ways that enabled them to resist the force of whatever medicine was once a cure. And as pharmaceutical companies migrated away from developing new antibiotics, focusing instead on better-paying sectors like cancer drugs, resistant infections flourished in recent decades.
A growing awareness of the problem among healthcare providers, researchers, and public leaders has started to reverse this trend. Those in the pharmaceutical industry also credit the 2011 federal GAIN Act, or Generating Antibiotic Incentives Now, which offered patent advantages and other benefits to companies that ventured back into antibiotics.
TXA709 is one of those products to benefit from this law, but the Monmouth Junction company is not alone. Debbie Hart, president and CEO of BioNJ, an advocacy group for the state’s biotech industry, said there are a number of Garden State companies working on new antibiotics and some 37 products in the pipeline nationwide. Economic incentives and other policy changes have helped spark this revival.
“There is a perfect storm right now given the combination of the need, the advances in the science, such as that underway at TAXIS, and the increase in incentives and potential incentives,” Hart said, “that is resulting in increased research in this important area.”
[related]The trend is encouraging, but more work is needed, noted Greg Mario, another founder of TAXIS who now serves as president and CEO. “So the pipeline is growing, but it’s not yet where it needs to be,” Mario said.
TXA709, is also unique in how it does its job. Unlike other antibiotics that attack the cell wall of a bacterium, or block the functions it needs to survive, Mario said their new drug interferes with the cell’s ability to divide and replicate — thus stopping the spread of the disease. In the lab, the new formulation has worked effectively against 200 different strains of MRSA, suggesting it can have a widespread impact on the infection.
“Our technology is very relevant,” Mario said. “This works in a way that no other drugs are working and it works when they fail.”
And when combined with another antibiotic, 20-year-old cefdinir, TXA709 is even more powerful, according to Pilch. While TXA709 works well alone against MRSA, in tandem the duo is even more effective and seems to reduce the likelihood of future antibiotic resistance.
“Current standard-of-care drugs for the treatment of MRSA infections are limited,” Pilch said. “Furthermore, resistance to these drugs is on the rise, and their clinical effectiveness is likely to diminish in the future.”
Also unusual is the way TXA709 can be given. It is one of only a handful of new antibiotics under development that can be taken orally, in pill form, instead of administered intravenously, Mario said. This can be a game-changer for patients, the difference between remaining in a hospital during a 10-day course of treatment or recuperating at home for some, if not all, of the time.
With the FDA’s approval to move to the next step, the company will start testing the drug in animals this fall. If there are no negative side effects, it will move on to human trials in the spring, Mario said. The drug could be on the market in early 2020, he said.
That timeline means the group still has time to develop a commercial name for the product, a process that usually involves an outside marketing expert and hundreds of thousands, if not millions, of dollars. The current name — TXA709 — was cobbled together from the following elements, Mario explained: “TX” stands for TAXIS Pharmaceuticals; “A” stands for Ajit Parhi, Ph.D., another TAXIS founder and the chemist who discovered the essential molecule involved: and “709” stands for the page number on the research log book, in which the team tracks its drug development work