It was a surprise to me (which may be in itself not surprising) that a novel therapeutic vaccine for tuberculosis from a small biotech company in Spain recently met a clinical milestone, from Phase I to Phase II. Archivel Farma S.L. of Badalona (Archivel) announced at the BIO 2010 meeting that it’s RUTI vaccine had induced immunity in uninfected subjects without adverse effects (Archivel PR 1) and that it was initiating a Phase II clinical trial in South Africa (Archivel PR 2). More surprising (again, to me at least) is that the intended use of the vaccine was in co-administration with isoniazid, a standard antibiotic for treating TB, meaning, that if successful, and according to Archivel, the treatment would eliminate the infection in one month. The standard course is nine months and poses compliance problems.
TB is one of the big three of infectious diseases (with HIV/AIDS and malaria) and has been the target of a ramped-up internatnional effort for more than 10 years, being both global (one-third of humans have latent infection, 1.8 million die each year, and it’s the leading cause of HIV-related mortality) (Aeras About TB) and increasingly drug resistant. One bright light has been that one of the earliest vaccines, called BCG (Bacillus Calmette-Guerin after its inventors, Wikipedia Article) and first used in the 1920s, confers protection against severe childhood TB, and is widely used in most of the world for that reason, but is unreliable against infections in adults. (The other bright light is that drugs do work and there is a considerable effort to develop new ones, c.f., the Global Alliance for TB Drug Development [TB Alliance] and the Critical Path to TB Drug Regimens [my posting of March 25].) New vaccines, whether an improvement on BCG or a new approach, face several challenges. They will need to work in uninfected, infected/latent, and infected/active populations, be tested and used in populations likely treated with BCG and possibly infected with HIV, and produce a greater immune response than that triggered by the typical infection with the risk of inducing an overly-active and harmful response (c.f., Martin 2005).
Into this breach has jumped several organizations. The Aeras Global TB Vaccination Foundation is a PDP (product development program) largely funded by the Gates Foundation and with new money from the UK government (Aeras). Their 2009 budget was about $54 million (Aeras 2009 Annual Report). Aeras works with a solid group of academic and commercial partners and has two preclinical and four clinical vaccine candidates in its pipeline. A similar Europe-based effort is the TB Vaccine Initiative (TBVI) which is based in the Netherlands and has about €3.745.000 ($4.5 million) in annual funding which they deploy primarily to EU academic groups. Rounding out the team is the Working Group on New TB Vaccines a part of an international “coordinating” organization, the Stop TB Partnership (Stop TB WG), and the WHO-based Developing Countries Vaccine Regulators Network (DCVRN) which a relatively new network of vaccine regulators from the US and UK and other nine countries, which is building the infrastructure for the trials (DCVRN). It is difficult for me to gauge the degree to which these groups are cooperating and coordinating, but there are ten vaccines in active trials as of 2009 according to the Stop TB Partnership (Vaccine Candidates 2009).
So what’s neat about Archivel’s RUTI? The following:
-it seems to be the only vaccine aimed at the latent stage of the infection (unaddressed need);
-it is complementary to an already-accepted and effective treatment (less technical and regulatory risk);
-has positive Phase I results (immune response and no adverse effects, Vilapana et al. 2010); and
-the Phase II will be done in a DCVRN country (South Africa) in individuals with or without concomitant HIV infection (Archivel PR 2).
In addition, Archivel, besides having an endearing website (c.f., Archivel Values) is a classic academic spinout. The founding scientist and now CSO, Pere-Joan Cardona, developed the vaccine on a contra-conventional concept that latent TB infections persist because the immune response produces non-replicating bacteria which, during the normal process of expulsion by the lung’s epithelial cells, are aerosolized, become active, and re-infect the lung (Archivel Hypothesis and New TB Drugs Interview). And to get his hypothesis out of the lab and into development (starting back in 2000), Dr. Cardona connected with and convinced a local venture capitalist, Felix Arias, to have his firm, bcnHighgrowth (Highgrowth) back him. Since then Archivel has been kept afloat with public money from alphabet agencies: subsidies from CIDEM (Centre for Business Innovation and Development) and loans from CDTI (Centre for Industrial Technological Development), ENISA (Empresa Nacional de Inversiones S.A.), and ICF (Catalan Finance Institute) (Archivel History).
Good luck, gang. Que les vayan bien.