Left: Martin Shkreli (photo courtesy of The Source). Right: A “kissing bug” (photo courtesy of Scienceline).
On August 29th, the U.S. Food and Drug Administration granted approval to benznidazole for use in children ages 2 to 12 years with Chagas disease. The approval is the first treatment of its kind to be approved in the U.S., and comes on the heels of a heated confrontation between advocates and pharmaceutical investors, including the now-jailed Martin Shkreli.
Chagas disease, or American trypanosomiasis, is caused by the Trypanosoma cruzi parasite and is transmitted by triatomine bugs, blood-sucking insects that have been given the horrific nickname “kissing bugs”, due to their tendency to bite (and subsequently feed upon blood from) people’s faces while they sleep. After the blood meal is taken, the bugs defecate infectious waste that easily can come in contact with victims’ eyes, mouth, or any open wounds. The disease can also be passed from mother to child during pregnancy, blood transfusions, and contaminated foods. It cannot be passed via direct transmission from person-to-person.
The acute phase of Chagas disease may be asymptomatic, but is otherwise mild: fever, fatigue, myalgia, headache, rash, loss of appetite, vomiting, and diarrhea. Swelling of the eye nearest the location of the bite is a marker for the disease. All these symptoms disappear within weeks, though 5% of young children experience severe infection or inflammation of the brain or heart muscle, which can lead to death.
The chronic phase of Chagas disease occurs decades later, when the parasite’s long-term presence within the body results in severe cardiac or intestinal complications that are irreversible, and can lead to death. These complications can include difficulty in digesting or passing food, irregular heartbeats, thinning tissues, and even heart failure. Persons infected with the parasite are 30% likely to suffer from these chronic symptoms later in life.
The disease is considered to be a neglected tropical disease (NTD), as it does not receive as much attention/funding as other diseases. Like other NTDs, it disproportionately affects the poorest people of the world. The triatomine bug vectors tend to inhabit domiciles made of more inexpensive and porous materials, such as thatch, straw, or adobe, which afford the insects a means of entering the homes and places to hide. Pharmaceutical companies are disinclined to produce treatments for NTDs as the most commonly afflicted persons cannot afford to pay for them, and thus costs are difficult to recover.
However, Chagas disease is a serious public health concern, as more than 60 million people are at risk for the disease throughout Latin and Central America, and more than 8 million people are infected with the disease. The CDC reports that more than 300,000 persons with T. cruzi infections are living in the U.S., though most of these people are assumed to have acquired the infections in countries endemic to the disease. A recent study of Latin-American born residents of Los Angeles county found that 1.24% tested positive for the disease.
The recently approved benznidazole can cure infants and young children with the disease with a 60-day course of treatment. Though it has been around for nearly fifty years and has received use in Central and South America, benznidazole had not been approved by the FDA for use in the U.S.; the CDC had been known to give it to doctors to dispense for compassionate treatment, but infrequently. In order to get the FDA to approve the drug, a pharmaceutical company needed to have registered it, and as previously discussed, this rarely happens with NTD treatments. This changed with respect to Chagas in 2015, when the FDA added the disease to the list of NTDs whose product applications could result in the award of priority review vouchers. Pharmaceutical companies that obtain these vouchers are able to fast-track production of applicable treatments… or sell these vouchers to other companies. Enter Martin Shkreli.
Shkreli, whose reputation is arguably best known for his 2015 acquisition of Daraprim–a drug for treating different parasitic infections (toxoplasmosis and cystoisosporiasis)–and subsequent inflation of the drug price $13.50 to $750, also had his eye on benznidazole, for similar reasons. In fact, Shkreli’s investor group announced that they would increase the price of benznidazole 100-fold, to $63,000-$95,000, should they acquire the voucher.
Activists within the medical and public health communities have since made known that price-gouging tactics such as Mr. Shkreli’s have dire consequences for patients who need these drugs, and are nowhere near financially well-off enough to pay at such inflated prices. For benznidazole, a plan was developed by Drugs for Neglected Disease Inititative (DNDI), a non-profit that specialized in bringing drugs for NCDs to market. The plan involved partnering with Chemo Group, another pharmaceutical company that had tried to register benznidazole prior to Chagas being added to the FDA’s list. Chemo Group was persuaded to produce benznidazole and price the drug at or below cost. DNDI also partnered with a non-profit associated with Chemo Group, Mundo Sano Foundation, that would put half of voucher profits toward programs that diagnose and treat those infected with T. cruzi.
The August 29th awarding of Chemo Group the voucher to produce benznidazole in the U.S. accomplishes several things. It makes the drug available in the U.S. for use against T. cruzi infections. It also sets a benchmark for collaborative agreements between pharmaceutical companies and public health non-profits that are set on providing treatments for NCDs. Finally, the Chemo Group approval potentially sets a precedent for eliminating the loophole in the priority review voucher process that has been exploited by unscrupulous persons looking to profit off of drugs that help the poorest people in the world. Perhaps similar partnerships as the Chemo Group’s will see this precedence and emerge to take on approvals for other NCD drugs.
The views reflected in this expert column are those of the individual authors and do not necessarily represent those of the O’Neill Institute for National and Global Health Law or Georgetown University. This blog is solely informational in nature, and not intended as a substitute for competent legal advice from a licensed and retained attorney in your state or country.