An inhalable tuberculosis vaccine based in part on delivery technology developed at Harvard University has been shown to be more effective in animal models than an injectable version, according to a recently published study, and is expected to enter Phase I safety trials next year, according to one of the study’s authors.
The vaccine is being developed and produced by non-profit group Medicines in Need, which plans to distribute it in developing nations through a royalty-free license from Harvard. The non-profit, also known as MEND, will likely commence the safety studies next year with an eye toward conducting clinical trials in South Africa, according to the researchers.
The vaccine is based in part on a rapid drying process for producing large porous particles originally developed in the lab of David Edwards, professor of the practice of biomedical engineering at Harvard’s School of Engineering and Applied Sciences.
In the spray-dry technique, a liquid vaccine preparation is sprayed through a heated gas to create a powder that can be stored without refrigeration. This is in contrast to many traditional vaccines, including the Bacillus Calmette-Guerin vaccine commonly used against TB, which are freeze-dried and require refrigerated storage and transportation, and clean water for reconstitution, the study’s authors said.
Harvard has worked with Edwards and MEND to ensure that the intellectual property developed by Edwards and owned by the school is managed and licensed in what they call a “socially responsible” manner.
Last year, Harvard’s Office of Technology Development and MEND entered into a licensing agreement that enables the non-profit to develop the vaccine technology in underdeveloped nations.
Under the terms of that agreement, Harvard granted MEND a royalty-free license to the technology for therapeutic use in developing nations. MEND is also pursuing commercial markets for its products in the developed world “for the sole purpose of supporting its charitable mission,” Harvard and MEND said in a statement.
MEND will pay Harvard an undisclosed royalty on revenues from those products and, under a gift-back mechanism, “most of those payments will be donated by Harvard back to MEND to support [its] effort to develop advanced treatments and preventative therapies for diseases of poverty,” Harvard said.
Edwards is no stranger to inhaled drugs. In the 1990s he spun out a biotech company called Advanced Inhalation Research to commercialize the technology. AIR was acquired by Boston-area biopharma Alkermes in 1999, and Alkermes is currently using the technology to develop inhalable medicines for several diseases prevalent in the developed world, such as diabetes.
In 2003 Edwards, along with a group of Harvard colleagues and undergraduates, founded MEND to use the technology to develop both spray-dried injectable and aerosolized vaccines targeting drug-resistant tuberculosis.
“One of the reasons that production will happen in South Africa is that in an ideal world, you take on the cost structure of the country in which you ultimately want to dispense the product.”
Two years later, Edwards’ Harvard group received a $7.6 million grant from the Bill and Melinda Gates Foundation’s “Grand Challenges in Global Health” project to support development of the vaccine, which it is conducting with MEND.
Part of that grant funded the animal-model study, which Harvard and MEND conducted in collaboration with scientists from the University of North Carolina, Chapel Hill; the Aeras Global TB Vaccine Foundation; and Manta Product Development in Cambridge, Mass. The results of that study were published in the March 25 issue of the Proceedings of the National Academy of Science.
The study sought efficacy of the vaccine by administering it in guinea pigs, which are believed to be an ideal system for monitoring TB progression due to similarities with the way TB infects them and humans, according to study co-author Anthony Hickey, professor of molecular pharmaceutics at the UNC School of Pharmacy.
The researchers found that among guinea pigs vaccinated with the aerosolized vaccine and subsequently exposed to TB, less than 1 percent of lung and spleen tissue showed effects of the disease. In comparison, in animals treated with the same dose of the injected vaccine, about 5 percent of lung tissue and 10 percent of spleen tissue showed disease effects.
Hickey, who is also on the scientific advisory board at MEND, said his lab at UNC was brought in on the study because of its expertise in aerosol drug delivery and its application for diseases such as TB. In addition, Hickey has worked independently on rifampicin and other vaccine antigens for TB, he said.
Along with the Harvard researchers, Hickey and colleagues have also developed aerosolized delivery technology for capreomycin, a TB antibiotic, which he said is expected to enter clinical trials next year.
As for the inhaled TB vaccine, Hickey said that MEND, under the direction of study co-author Bernard Fourie operating out of the non-profit’s South Africa office, is leading the production effort, with assistance from Andre Germishuizen, who spent a year as a postdoc in Edwards’ lab at Harvard.
“Initially we’ll need to do safety studies [in animals], and that’s going to be next year; and then ultimately we’ll want to do clinical studies, which will probably be in South Africa,” Hickey said.
Hickey has also previously started two companies, both based in Research Triangle Park, NC: Oriel Therapeutics, which is developing dry powder-inhalation therapeutics; and Cirrus Pharmaceuticals, a formulation-development company. He said that Cirrus has performed some in vitro testing for the MEND group as part of the TB vaccine program, but will not be involved in production.
“Whether they would, at some point in the future, request that more work be done by Cirrus, I can’t say,” Hickey said. “They will go to whichever company makes sense, and one of the reasons that production will happen in South Africa is that in an ideal world, you take on the cost structure of the country in which you ultimately want to dispense the product.
“These days it would probably make sense to do as much as possible for the developing world in the developing world because of the cost involved,” Hickey added.