Last February, a sick infant named KJ received a gene-editing treatment made just for him. Created in just six months, it was meant to correct a rare genetic mutation that was causing toxic ammonia to build up in his small body. The treatment likely saved his life, and baby KJ was discharged from the hospital in June.
Now, a new startup called Aurora Therapeutics, cofounded by gene-editing pioneer Jennifer Doudna, is aiming to scale such treatments to many more patients with rare diseases. Doudna is one of the inventors of the gene-editing system known as Crispr, and won a Nobel Prize in 2020 for her work on the technology.
Aurora plans to take advantage of a new regulatory pathway announced by Food and Drug Administration officials Marty Makary and Vinay Prasad in the fall. The new program, called the “plausible mechanism pathway,” allows the FDA to approve personalized treatments for rare and fatal diseases based on data from just a handful of patients, according to Makary and Prasad in a New England Journal of Medicine article.
Typically, new drugs must be tested in hundreds, if not thousands, of patients in order to get regulatory approval. For drug trials of rare diseases, it’s difficult to recruit that many patients because so few people have the disease. The new FDA pathway provides a way for these types of drugs to be approved when a large, randomized trial isn’t possible.
“Once a manufacturer has demonstrated success with several consecutive patients with different bespoke therapies, the FDA will move toward granting marketing authorization for the product,” Makary and Prasad say in their article. Drug companies will then be able to use data from those patients to get similar drugs approved that are based on the same underlying technology.
That is key for Aurora, which will initially focus on treating a metabolic disorder called phenylketonuria, or PKU, that’s screened for at birth. The disease leads to toxic levels of phenylalanine, a building block of protein, in the blood. Patients with PKU must eat a highly restrictive low-protein diet. Without early treatment and monitoring, PKU can hinder brain development and impair cognitive functions. An estimated 13,500 people in the US are living with the disease.
“There are a lot of patients that could benefit from this therapy. But the problem is, you have many, many mutations—over a thousand—that cause this disease,” says Edward Kaye, CEO of Aurora Therapeutics and a pediatric neurologist.
Crispr works by using a guide RNA to deliver an editing molecule to a desired location in the genome. The guide RNA is like a car’s GPS—it goes where it’s programmed to go. In the case of baby KJ, scientists built a guide RNA to target his specific genetic mutation. It’s why his treatment only works for him.
Aurora’s strategy involves swapping out that guide RNA to make several versions of a PKU therapy that address different mutations. Previously, the FDA would have considered every version a totally new drug, each requiring its own clinical trial. But now, Aurora will be able to use the same technology platform to treat many mutations that cause PKU with less regulatory red tape.
Kaye says the company will use base editing, a more precise form of Crispr, and will have a standardized process to streamline the design and manufacturing of its therapies.
“We are very much about no mutation left behind,” says Fyodor Urnov, Aurora’s cofounder and a genome editing scientist at UC Berkeley. Urnov and several of his colleagues at Berkeley’s Innovative Genomics Institute, which Doudna established in 2015, were involved in designing baby KJ’s treatment.
