Neglected tropical diseases (NTDs) impact more than one in six people worldwide, often the poorest, but are allocated less than 0.5 percent of global pharmaceutical investment. Yet, new approvals continue to be a trickle compared to what is happening elsewhere in drug development.
Nevertheless, there’s room for cautious optimism. And much of it has to do with priority review vouchers (PRVs). PRVs for NTDs are granted if a pharmaceutical company obtains approval from the Food and Drug Administration (FDA) for a drug or vaccine for a neglected disease indication. The vouchers provide companies with the option for a six-month expedited review of another product in their development portfolio instead of the standard 10-month period, or a voucher can be sold to another company, as was the case when United Therapeutics sold its voucher to AbbVie for $ 350 million in 2015.
The first PRV for NTDs was issued in 2008 for Coartem (artemether/lumefantrine), an artemisinin-based combination therapy developed by Novartis for treating malaria. Coartem is now a first-line treatment for malaria across Africa and Southeast Asia.
After a sluggish start following the creation of the PRV program for neglected tropical diseases in 2007, recently the issuance of PRVs in exchange for neglected disease drug approvals has picked up considerably. As of November 2018, 7 PRVs have been awarded in the following tropical disease categories: malaria, tuberculosis, leishmaniasis, cholera, river blindness, and Chagas disease.
From a public health perspective neglected tropical disease programs – from mass administration campaigns to donation programs to new drug development – offer a substantial return on investment. It is estimated that if countries achieve the World Health Organization’s 2020 targets, over $ 620 billion in increased productivity would be generated between 2015 and 2030.
From a private equity perspective, however, the return on investment narrative is different. It’s obvious that drug development activity is sensitive to expected future revenues in the market. This means that when deciding to invest in R&D, and in directing investments to particular products, there needs to be the expectation of a positive return on investment, which implies resources to pay for the new approvals. That money is still not there in most of the developing world. Therefore, push and pull incentives are needed to stimulate investment. Thus far, the most successful pull incentive is the PRV.
Notable advances for which PRVs were issued recently include Krintafel (tafenoquine), approved in July this year. Krintafel is the first new anti-malarial approved in 18 years. It can cure or prevent relapses of the Plasmodium Vivax infection. In June 2018, the FDA approved moxidectin, a treatment for river blindness or onchocerciasis in patients aged 12 years and older. Moxidectin is the first new approval for onchocersiasis in over 30 years, and is considered an improvement relative to the existing standard of care, ivermectin. Last year, the FDA granted approval to benznidazole for use in children ages 2 to 12 years old with Chagas disease. Benznidazole is the first treatment approved in the U.S. for the treatment of Chagas disease. And, in 2012, Sirturo (bedaquiline) was approved as the first new molecular entity targeting tuberculosis in 50 years.
PRVs have been criticized because there is no incentive for the companies and public-private partnerships, which receive vouchers after developing and obtaining regulatory approval for NTD drugs, to facilitate access to the patients who need them.
However, the public-private partnership Drugs for Neglected Diseases Initiative and company Insud Pharma awarded a PRV for obtaining regulatory approval for benznidazole in August 2017 have apportioned part of the value of the voucher towards patient access. It is hoped that other partnerships and companies will follow suit.