Roy Vagelos remembers the thrill in the 1980s when he saw test results of his company’s prototype drug against river blindness and the parasitic worm, Onchocerca volvulus, that causes pain, scarring and blindness in hundreds of thousands of people across Africa and Central and South America.
Scientists at Merck led by William Campbell — who last year shared the Nobel Prize for medicine for the work — showed that a variant of avermectin, a drug originally developed to combat parasites in dogs, could prove effective in tackling onchocerciasis in humans. Under Mr Vagelos, who from the position of head of research had been appointed Merck’s chief executive, the company would launch a programme to donate as much of the drug as was required for as long as necessary.
“It was one of the most exciting results we had ever seen,” Mr Vagelos recalls, looking back on his time at Merck. “I was a physician who switched to basic research, then drug discovery, as a way to close the loop to get important new drugs to treat people beyond the normal small groups a doctor can help.”
Yet more than three decades after Merck began its programme, the burden of the disease remains heavy, raising questions about whether international goals for its elimination by 2025 are realistic.
Little doubt exists about the continued need for the drug, called ivermectin or Mectizan, or some improved version of it. Onchocerciasis affects an estimated 37m people, nearly all in Africa.
It occurs close to fast-flowing rivers, breeding grounds for blackflies whose bites transmit the worms. These grow into adults (macrofilariae) in humans and cluster in nodules, where they produce large quantities of young worms (microfilariae) some of which are transmitted back into flies.
The microfilariae cause inflammation leading to severe itching, loss of vision and sometimes epilepsy and premature death. The stigma of the disease forces infected people to emigrate from fertile land and cuts productivity.
Large-scale programmes to spray insecticides to kill the flies in the 1970s had some success but lost momentum. In the absence of government funding, Merck has donated treatments since 1987 — 176m last year — and has provided an average additional $5m annually to help with delivery.
In South and Central America, efforts to eliminate the disease have proved successful everywhere except a stretch of the Amazon between Brazil and Venezuela. In Africa, progress has been far slower and concentrated instead on control of the disease. Sharp reductions in the disease’s burden have been recorded in Niger and Malawi.
One measure required is to raise the frequency of Mectizan use across Africa from once to twice or even four times a year. “The time is now,” says Frank Richards of the Carter Centre — the non-profit founded by former US President Jimmy Carter and his wife Rosalynn — and a veteran of the treatment programmes.
Although Mectizan is generally safe, it is dangerous to patients in some parts of Africa who are infected with the disease loa loa, commonly known as “eye worm”. Given that some evidence exists of emerging resistance to the treatment, scientists are seeking new drugs.
“Mectizan has been phenomenally successful, hugely reducing the burden and saving the sight of millions,” says Robert Don from the Drugs for Neglected Diseases Initiative, a charity involved in several research programmes. But, he adds, “we need a toolbox of improved drugs, diagnostics, sanitation and vector control.”
Supplies of Mectizan are vulnerable to being affected by such as “distributor fatigue” among the largely unpaid community volunteers who administer drugs to local people. Capacity and expertise to kill the insects is limited. Civil wars and other political unrest reduce opportunities to fight the disease in several countries.
The extent of the World Health Organisation’s support prompts some scepticism. Last year, its programme for onchocerciasis control was abolished. The Expanded Special Project for Elimination of Neglected Tropical Diseases that replaced it has a remit far beyond river blindness and less funding.
“When demand is there, supply has always been, too,” says Ken Gustavsen, who runs Merck’s Mectizan donation programme for both onchocerciasis and lymphatic filariasis, which also uses the drug in combination with others. “We’re still aiming for onchocerciasis elimination by about 2025.”
“We need more flexible approaches,” Mr Richards cautions. “These parasites want to play the long game. They wait for us to tire.”