No Kiddin’

Last week I was pleased to attend the 5th anniversary reception for the Cambridge MA-based Institute for Pediatric Innovation (IPI), a not-for-profit founded by one of my technology transfer mentors, Don Lombardi.  After a career in business and technology transfer at Children’s Hospital Boston, Don started IPI to address the lack of new technology and therapies to treat children.  Its mission is “to identify which new devices and drugs clinicians need to provide better pediatric health care, and strive to turn those into available products,” and to date, the IPI has built a network of hospital and clinicians as sources of technology but has the ongoing challenges of funding and converting prototypes into products.

Of course, improving pediatric health is not a problem of the US only.  In developing world, in addition to the dangers of birth (the main cause) and inadequate nutrition causing children’s mortality, infectious diseases like pneumonia, diarrhea, HIV/AIDS, malaria, and rabies take their toll resulting in about 8 million children under the age of five dying each year (Global Health Council summary).  Aarthi Rao summarized the problem succinctly in a recent post (Center for Global Health Policy Assessment blog, “But What About the Kids,” Rao post), noting three needs:  access to and application of existing tools and methods (a problem in health care delivery), adaptation of existing technology and treatments for pediatric use (e.g., development of pediatric dosing and safety data for drugs, see WHO’s Essential Medicines for Children, WHO Meds for Kids), and development of new technologies specific to kids.  NGOs, international agencies, and foundations are focused mostly on the first area and somewhat on the second, and so I see a need and an opportunity for companies in the third, applying technology to improve ROW (rest-of-world) pediatric health.  Here are a few specific needs I have noted:

  • Tuberculosis diagnostic: since children cannot cough up enough sputum for an adequate standard diagnostic sample, a better method is needed (Rao above and WHO Fact Sheet);
  • Diagnostic to differentiate fever:  sick kids have fevers but proper treatment requires knowing the cause, so a diagnostic that can differentiate between malaria and pneumonia, for example, is needed (see BVGH IQ Prize Case Statement);
  • Pulse oximetry and oxygen delivery:  studies have shown that a reliable system of measuring blood oxygen and delivery of oxygen as needed can reduce child mortality from pneumonia by 35% (Duke et al 2009) and some simple oximeters have been prototyped (e.g., Zaman lab);
  • Sickle cell treatment:  as I mentioned in a previous posting (“A Really Neglected Disease,” 7/29/10),  underlying sickle cell disease in children in Africa is likely a contributing factor to upwards of 250,000 deaths per year, so a treatment will be life-saving (see All Africa article); and
  • Vaccines:  some infectious microbes have serotypes that are specific to kids whose developing immune systems make them vulnerable, so new vaccines are needed (e.g., bacterial meningitis and dengue).

But getting new technology development funded is the rub.  In the pediatric disease field there are huge donor-funded programs to improve health care delivery (as there should be), but few funders who understand the risks and rewards of technology development.  The Bill and Melinda Gates Foundation is one of the few foundations that is trying to and recently announced that one of its Grand Challenges will be for “scientists, innovators and entrepreneurs to seize the opportunity to contribute to the field of family health through the discovery and development of medicines, medical devices, diagnostics and other lifesaving tools.”  It will be funded at $35 million (Gates press release) and I hope will have advice from successful entrepreneurs.  There are currently small grants are available through the Grand Challenges Explorations program in which Round 6 included maternal and infant health as a goal (Explorations), but as I have noted previously the grantors favor academics.  Also recently the Gates joined USAID, the governments of Norway and Canada, and the World Bank to launch the Saving Lives At Birth Grand Challenge (Saving Lives) to fund innovations in both delivery and technology.  Of 19 finalist organizations under consideration for a share of $14 million in funding, seven have a technology component (Finalists), and if a few of these receive adequate funding and help from experienced product developers, one may actually create something that saves lives at birth.

One would think that companies with global health corporate responsibility programs would have an interest supporting technology development for neglected pediatric disease.  Two candidates are Alere, an international diagnostics company that has donated HIV/AIDS diagnostics (Alere), and Laerdal Global Health, which sells maternal and neonatal health products and training (Laerdal).  As for the big corporations, in 2010, the Johnson and Johnson Company made a five-year but unspecified dollar commitment to the WHO’s “Every Woman, Every Child” program (JnJ press release).  Although the press release mentions research and development of new medicines as a goal, the program website does not (Every Woman).  This month the General Electric Foundation provided Jhpiego, a Johns Hopkins University affiliate, with $1.6 million to “develop low-cost, lifesaving technologies that can transform health care for women and children in developing countries” (Jhpiego press release).  That is generous but limited to JHU and not much money for the intended “early-stage innovation and then, for selected projects, field-testing and product introduction.”  Bottom line:  cultivation of the corporate sector is needed.

Meanwhile back at the  Institute for Pediatric Innovation,  there is one project with a global health slant which is to perform a “detailed review of the medical anthropology” to “help advance pharmaceutical reformulation for children by sensitizing drug developers and marketers to important cultural and social issues” (Evaluating Global Reformulation Needs, IPI project).  I’m unclear on the concept and the results are still forthcoming.  My suggestion to Don to have a bigger impact on global pediatric needs:  review the IPI technology portfolio for opportunities that have global health relevance, write-up development, funding plans, and strong arguments to convince potential licensees that products for kids can have profit margins, and start knocking on doors in the for-profit world.

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?