One of the Holy Grails of global health (there are many) is delivery of vaccines via inhalation rather than injection. The advantages are major: less potentially infectious waste (needles), less of a need for medically-trained distributors, no need for refrigeration (the “cold chain” problem), more kid-friendly, and less expensive to prepare and package. WHO, academic groups, and a few companies (e.g., the not-for-profit, Medicines in Need [MEND]) are working on inhalation delivery, and progress has been slow. So, when it was announced in August that a product was close to human trials (Science News), I was interested in learning the full story, especially knowing the challenges of technology development and product commercialization.
Dr. Robert Sievers made the announcement at the 238th [!] meeting of the American Chemical Society. He is a professor of chemistry at the University of Colorado (Sievers Bio) and has been working on using super critical carbon dioxide, which at high pressure is a super-strong solvent, to formulate drugs for more than eight years. In 2002, he and others formed a company, Aktiv-Dry LLC (Aktiv-Dry), with a license to the basic technology from the University and funding apparently out of their own pockets to provide “dry powder processing solutions for the vaccine, pharmaceutical, and biotechnology industries.”
Over the next couple of years, the Aktiv-Dry management put together a plan for a measles vaccine development that included five academic groups, two companies (BD Technologies and Asperonics), the Indian Serum Institute, and the Centers for Disease Control and Prevention, applied to the Gates Foundation’s Grand Challenges in Global Health Initiative through the Foundation for the National Institutes of Health, and, in late 2005, was awarded a $19.5 M grant. Although a good chunk of money, the grant was to cover a large amount of work:
-design of a formulation likely to work and be nontoxic;
-conduct of preclinical safety and efficacy tests through nonhuman primates;
-design and testing of a easy/cheap-to-make delivery device;
-scale up and transfer of the dry powder manufacturing process to the Serum Institute;
-preparation of sufficient formulated vaccine and devices for an initial safety study in humans; and
-conduct of the initial human study.
And, in an exemplary “virtual company” mode, Aktiv-Dry has done it all up to the last step (although I could not find published confirmation that the data from the one-year follow up challenge test in Rhesus monkeys due this past summer, showed adequate protection, a key milestone).
If the initial trial results justify further development, Aktiv-Dry needs to raise sufficient capital for designing and conducting Phase I and II safety and efficacy studies, manufacturing sufficient study material and devices (while preparing all the required documentation for registration), and find a partner to complete the trials and registration and to commit to a commercialization (distribution) plan. Even if the company utilizes the subsidized testing route provided by the WHO’s measles aerosol immunization program (WHO Vaccine Research), I am guessing that another $20 M is needed. If the Gates Foundation were acting like a venture capital firm rather than a grantor, it would be closely involved in the management of the company and be ready to “re-up.” Perhaps it is, but my guess is that, given its past emphasis on research and not development, the Foundation’s planners are not prepared for full funding of the effort.
With an eight-person staff (apparently none in business or clinical development), is Aktiv-Dry ready for the next stage? The company is developing another, more commercial product line (delivery of iRNA therapeutics) which may be a distraction. I hope the management has the commitment and smarts to continue, since not only will an inhalable vaccine contribute to increasing the global measles vaccination rate (now at about 80%) and reduce annual mortality (now about 200,000) (WHO Vaccine Report), it will establish a technology that may be applied to the other, urgently needed, global health vaccines.