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Friday, September 7, 2018

The Problematic Market for Snakebite Antivenoms

The World Health Organization reports: "About 5.4 million snake bites occur each year, resulting in 1.8 to 2.7 million cases of envenomings (poisoning from snake bites).There are between 81 410 and 137 880 deaths and around three times as many amputations and other permanent disabilities each year. ... Bites by venomous snakes can cause acute medical emergencies involving severe paralysis that may prevent breathing, cause bleeding disorders that can lead to fatal haemorrhage, cause irreversible kidney failure and severe local tissue destruction that can cause permanent disability and limb amputation. ... In contrast to many other serious health conditions, a highly effective treatment exists. Most deaths and serious consequences from snake bites are entirely preventable by making safe and effective antivenoms more widely available and accessible. High quality snake antivenoms are the only effective treatment to prevent or reverse most of the venomous effects of snake bites."

Many of those who die for lack of antivenom treatments are among the poorest people in the world: about half are in India, and another third in countries of Africa. The antivenom needs to be available quickly, which means nearby, which means facilities for storage.  For the private sector, there isn't a lot of profit potential in  researching and manufacturing antivenom, nor for distributing it around the world to appropriate storage facilities. Those who worry about international public health have traditionally focused on diseases, and snakebite isn't a disease.

But in the last year or two, snakebite antivenom has gotten more attention. Organizations like Médecins Sans Frontières have been raising the issue for years. In a meeting in May, the "World Health Assembly in Geneva [the decision-making body for the World Health Organization] demanded action" and passed a resolution. So there's that. But a number of obstacles remain.

The current method of producing antivenom is done via animals. As noted in an article in the journal of the Royal Society of Chemistry:
"Meanwhile, new approaches to make antivenom production simpler and cheaper are being developed. Currently, anti-venom production is laborious. Venom is extracted from a snake, then administered to a horse or a sheep in small doses to evoke an immune response. The animal’s blood is then drawn and purified to obtain antibodies that act against venoms. One promising approach that would make antivenom production quicker and cheaper is recombinant antivenoms. These antivenoms are produced by expressing therapeutic monoclonal antibodies, which can bind to a specific protein or a toxin in snake venom, in an engineered cell line."

Different snakes have different venoms, and thus require different antivenoms. Ideally, there would be a universal antivenom, but researchers say this seems a decade away.

There seems to be a race-to-the-bottom phenomenon in this market. Potential producers of antivenoms in high-income countries face high research costs. In the areas where snakebite occurs, doses of high-quality antivenom are quite expensive relative to people's incomes, and sometimes several doses are needed. Thus, it becomes common to give patients less than a full dose, and hope for the best. The health care providers who administer the venom often lack training. It becomes common for low-quality medications to enter the market, which in these countries is largely unregulated. In fact, most antivenom products available in these countries have almost never been through a standard clinical trial, looking at effectiveness and possible side-effects. Potential producers for high quality antivenom have been withdrawing from the market.

And the market itself isn't all that big: "Added into all this is the issue that the antivenom market simply isn’t that lucrative for big pharma. Market research firm Transparency Market Research put the global antivenom market at $1.7 billion (£1.3 billion) in 2016. Sanofi Pasteur halted production of its FAV-Afrique antivenom, effective for several African snakes, in 2010. Sanofi cited cut-price competition for the withdrawal."

There has been a string of articles over the last few years expressing concerns that supplies of antivenom are about to run out. It seems as if some institution-building is needed here if the supply of antivenoms is going to rise to meet the scale of the problem.

 Here's an overview from a few years ago of the state of the research pipeline for snake antivenom. Here's a more recent overview from the World Health Organization on guidelines for production, control, and regulation of snake antivenoms.