Holy Grail Horse Race

Those of you who follow this blog closely will likely realize the importance of this posting; it’s number 53 and therefore marks delivery of a full year of quality insight and analysis in global health, at least, I hope so.  You may also note that it has a new look:  a new layout, more blue and less green color, easier-to-read font, and a Tag Cloud to find postings.  Given the anniversary, I am updating a posting from about a year ago.

In my 10/28/09 posting, I described an effort to develop an inhaleable, dry-powder measles vaccine, a holy grail for public health since it has the potential to lower costs and speed delivery significantly (less infectious waste, need for refrigeration and skilled vaccinators, expense to prepare and package) for a disease that still infects 30 million people each year and kills about 100,000 despite a world-wide vaccination program.  The specific vaccine is a product of Aktiv-Dry LLC (Aktiv-Dry), a 2002 spin out from the University of Colorado, which uses a dry-powder preparation method invented by Dr. Robert Sievers.  The program has $20 million in funding from the Gates Foundation, and in my original posting, I posited the funding and company staffing may be insufficient to get the vaccine through trials.

What’s been the clinical progress?  At the Gates Foundation website, a project summary states the Phase 1 trial would start in 2009 (Gates Challenges), but apparently it did not.  An Aktiv-Dry press release set the start of Phase 1 in 2010, but there is no news on the company website (Aktiv-Dry News) or the website of its subsidiary, Aktivax (Aktivax), which was formed in 2008 as a dry powder vaccine manufacturer.  Aktiv-Dry’s partner for the trial is the for-profit Serum Institute of India, one of the world’s largest supplier of the current measles vaccine, as well as many other “rest-of-world” products (Serum Institute).  In May 2010, Dr. Seivers stated that the Serum Institute’s trial would start in the summer (Science Daily article) or later in the year (CBS article).  So if someone has registered the trial or is recruiting for it, she/he ain’t talking.

Interestingly, the dry-powder approach is in a race with the liquid aerosols through the WHO Gates-funded Measles Aerosol program (WHO program) which started in 2002 with the goal of licensure  of a vaccine in 2008.  It is evaluating three liquid aerosol delivery devices and, as a late starter, the Aktiv-Dry vaccine.  At least one of these devices is being tested by the Serum Institute and completed Phase 1 successfully in May 2010 (India Express article).  In theory, the dry powder approach has several advantages over the liquid, principally that the diluents could be a source of contamination and the delivery equipment is more complicated, although, as with all inhaled medicines, dose control is the biggest problem (c.f., Papania 2003).  If a pharma company were managing the comparison, they’d hold on the liquid aerosol trials until the dry powder’s safety was indicated in Phase 1 and then go to Phase 2 with the most promising, hence the apparent delay in the Aktiv-Dry/Serum Institute Phase 1 is puzzling.  But since the WHO program has multiple “partners” (more than 30 institutions are listed), management is likely by committee and slow.

Also of note is that other dry powder inhaled vaccines are under development (I am differentiating between vaccines which are inhaled into the lungs and intranasal vaccines, like FluMist, which are deposited into the nasal passages). The Gates Foundation gave $8.3 million to the not-for-profit, Medicine in Need (MEND) to create dry-powder versions of the TB vaccine and others (MEND PR), but, although the TB trials were to start in 2009 (Genome Web article), no progress has been reported.  There is also for-profit interest in dry powder vaccines.  LigoCyte, a venture-backed start up in Montana, has dry powder vaccine for norovirus which was started in Phase 1 in 2007 and was reported as safe in April 2010 (LigoCyte PR) and an anthrax vaccine in works (NCBI article).  One of their investors is a major supplier of global vaccines, GlaxoSmithKline.   Another company, Oriel Therapeutics, was an University of North Carolina spin out based on a powder formulation process (UNC Spinouts) that was purchased this year by Sandoz, the generic drug division of Novartis, a big vaccine-maker (WSJ article).  Although the company’s pipeline comprosed two dry powder drugs not vaccines, one of the founders, Tony Hickey, made but not tested a dry powder ‘flu vaccine (AAPS article) and was involved in the preclinical testing of the MEND TB vaccine (PNAS article).

In the race for the first inhaled vaccine for a global disease, I’m switching horses from Aktiv-Dry/Serum Institute/Gates, since it seems their management structure is delaying the trials, and backing the dark horse, Sandoz/Novartis, who I am betting sees a huge dual market opportunity in storable, transportable, and easy-to-use world-wide vaccines.

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