How do you get a Priority Review Voucher without human clinical data? The Animal Rule.

There are two active Priority Review Voucher (PRV) programs that allow sponsors to sell and monetize a voucher, the Tropical Disease PRV program and the Rare Pediatric Disease PRV program. One of the key differences between them is that the Rare Pediatric Disease PRV pathway explicitly requires human clinical trials, whereas the Tropical Disease PRV pathway doesn’t necessarily.

So how do you get a PRV without running a human clinical trial. The Animal Rule.

The Animal Rule is an FDA pathway that can allow the agency to approve a drug for human use based on adequate and well-controlled animal studies when human efficacy studies would be unethical or not feasible to conduct. The first drug approved under this pathway was pyridostigmine bromide in 2003, developed by the US Army as prophylaxis against the lethal effects of soman nerve agent poisoning. Since then, another 16 products have been approved via the Animal Rule.

Tpoxx (tecovirimat), a treatment for smallpox, was developed by SIGA Technologies, Inc. and approved by the FDA in July 2018. It was approved under the Animal Rule, and SIGA was awarded a Material Threat Medical Countermeasure PRV alongside that approval. This was the first, and so far only, product approved via the Animal Rule that was also eligible for a PRV. Now the Material Threat Medical Countermeasure PRV program isn’t one of the PRV programs I mentioned above and that is because this voucher program expired in October 2023 and the FDA can no longer issue vouchers of this type.

A company I’ve been following this year that is looking to capitalize on the Animal Rule is Island Pharmaceuticals [Note I have no financial position, direct or indirect, and no financial interest in the company]. They are a small biotech in Australia developing assets for Tropical Diseases via the Animal Rule and in their recent disclosures have stated that the FDA has confirmed they can proceed through clinical development via the Animal Rule pathway and would be eligible for a Tropical Disease PRV should the product gain FDA approval.

Reading about Island Pharmaceuticals is what first made me aware of the Animal Rule pathway. It was not something I had come across before, and I find it fascinating how companies are using the commercial value of PRVs in different ways. From my dataset, only 16 Tropical Disease PRVs have been issued, compared with 72 Rare Pediatric Disease PRVs, despite the Tropical Disease PRV program being the first of the PRV programs. Rare pediatric diseases understandably dominate the news cycle, given how emotive and historically neglected this area of research has been, but I wanted this article to show some love to the tropical disease research still going on quietly across the world.