PET Friendly

Just about everywhere in the world, rabies is an endemic and invariably fatal disease afflicting many mammals, including us.  It is caused by a rhabdovirus that is present in an infected animal’s saliva through which it can be inoculated into other animals via bite wounds.  The virus enters peripheral nerves, evades the immune system, spreads to the central nervous system, and causes a lethal encephalomyelitis (WHO Report 2007).  The incubation period is typically 1-3 months but may be as short as days or as long as years, and death occurs within a few days of clinical manifestation.  Fortunately, the disease is both preventable by vaccination of reservoir animals and humans and treatable if the victim is promptly administered a regime of vaccine and anti-rabies antibodies called Post Exposure Therapy (PET) (WHO Position Paper 2007).

According to the WHO, about 20 million people are bitten by suspect rabid animals each year, 40% of whom are children under 15 years of age and more than 55,000 of whom die (WHO Fact Sheet).  In most of the developed world, widespread and mandatory immunization of dogs has greatly reduced rabies incidence, e.g., in the US there are fewer than 40,000 annual exposures and very few deaths (Up To Date entry on rabies).  In the developing world, rabies is another neglected disease.  India has the highest number of exposures, about 5 million per year, and deaths, about 20,000 or 2/100,000 population at risk (the highest per country), and in Africa there are 24,000 annual deaths or about 4/100,000 population at risk (WHO Fact Sheet).

Unlike some neglected diseases though, the neglect does not involve the lack of a safe and effective vaccine.  For example, in India there at least six vaccines on the market, made by both international and domestic vaccine companies (Economic Times article 1):

  • Rabipur made by a Novartis/Aventis joint venture with a 60% market share (as measured by dollars not doses);
  • Verorab by Sanofi-Aventis, 24% share;
  • Vaxirab by Zydus Cadila, 15% share;
  • Indirab  by Bharat Biotech;
  • Rabivax by Serum Institute; and
  • Abhayrab by Indian Immunologicals Ltd.

But the challenges to delivering effective PET in India and elsewhere are multiple:

  • PET needs to start immediately after suspected exposure;
  • The vaccination process requires multiple injections (2 to 8 depending the route and the vaccine) on each of 4-5 days over a 30-day period;
  • The vaccines require “cold chain” storage and distribution (40-45 to 8 degrees F);
  • To be most effective, PET should include a local injection of rabies antibodies to bind up the virus until the body can respond to the vaccine and make its own (WHO Use of RIG); and
  • Since the current antibodies are derived from equine or (rarely) human sources, their quality and availability vary.

On the plus side, the vaccine manufacturing process is proven and cell-based (leading to a low barrier to entry, competition, and lower prices) and the vaccine be stored for three years (allowing bulk purchasing by public sector agencies).  Also on the plus side for India and possibly the rest of the developing world is that one large, not-for-profit biotech company, Indian Immunologicals Ltd. (IIL), has developed its own vaccine and is using a franchise model to distribute it to under-served rural and semi-urban populations.  IIL is a wholly-owned subsidiary of the Indian government’s National Dairy Development Board (NDDB) and is one of India’s largest biotech companies with sales of $52 million in 2010 (Economic Times article 2).  IIL was created in the 1980s to develop and provide low-cost animal vaccines to Indian agri-business, moved into human vaccines, specifically a rabies vaccine, in the late 1990s, and has as its tagline, “immunity made affordable” (IIL Mission).  According to a recent study of the IIL franchise system (Masum et al 2011), IIL sells about 1 million doses each year through its franchisees (about 4% of the total sold in India) while selling 3.3 million doses to government hospitals and clinics generating revenue of $16.2 million (2009 data).  IIL’s franchise physicians are in 3000 locations, and IIL supplies them with vaccine to be sold at a set price (about 10-30% lower than other vaccines) and refrigerators for storage.  While the authors note that they did not have access to the financial data needed to determine the profitability of the franchise business, they report that IIL had “indicated” a profit margin of 15% for it.  Further, the authors note the franchise approach has allowed for lower distribution costs and direct-to-consumer marketing and that IIL plans to expand the line of vaccines offered to include its products for tetanus, measles, and diphtheria/pertussis/tetanus (see also Abhay Clinic presentation).

What may be next for IIL and its vaccine franchise distribution system?  Putting on my BD hat and using what little data I have and an excellent presentation by SK Dash from the Fifth Annual World Vaccine Summit 2011 (Dash 2011), here are my suggestions:

  • Expand to more locations, especially urban, to sell both prophylactic and therapeutic vaccines at competitive prices (the current market private-pay market is about $50 million [Dash 2011] and the current price is about $6.75 per dose [Hello Ap post]);
  • Expand the product line to include other companies’ vaccines, going with the lowest-priced products and passing on the savings;
  • Add a PET antibody product preferably one made by cell culture either by IIL or another company (e.g., the Serum Institute of India is working with MassBiologics, itself a public entity, on a monoclonal rabies antibody [University of Massachusetts press release 2010)];
  • Use the system to distribute a rabies vaccine for dogs which is the best way to prevent the disease (see Ilona Otter blog, for a discussion of the economics of canine vaccination);
  • Through a tie-in with an insurance provider, use the clinics to offer rabies insurance for the cost of PET; and
  • Help other countries set up similar vaccine franchise systems (according to Masum et al., the government of the Philippines started its version in 2007).

Other ideas?

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