Now, a new startup called Aurora Therapeutics, founded by gene-editing pioneer Jennifer Doudna, is aiming to expand such treatments to many more patients with rare diseases. Doudna is one of the inventors of a gene-editing system called CRISPR, and won the Nobel Prize in 2020 for his work on the technology.
Aurora plans to take advantage of a new regulatory pathway announced by Food and Drug Administration officials Marty Macri and Vinay Prasad in the fall. The new program, called the “plausible mechanism pathway,” allows the FDA to approve individual treatments for rare and deadly diseases based on data from a small handful of patients, according to Macri and Prasad in an article in the New England Journal of Medicine.
Typically, new drugs must be tested on hundreds, if not thousands, of patients to receive regulatory approval. For drug trials of rare diseases, it is difficult to recruit so many patients because so few people have the disease. The new FDA pathway provides a way to approve these types of drugs when a large, randomized trial is not possible.
“Once a manufacturer has demonstrated success with a number of patients consistently with different specific treatments, the FDA will move toward granting marketing authorization for the product,” Macri and Prasad said in their article. Drug companies would then be able to approve similar drugs based on the same underlying technology using those patients’ data.
This is important for Aurora, which will initially focus on treating a metabolic disorder called phenylketonuria, or PKU, which is screened for at birth. The disease leads to toxic levels of phenylalanine, the building block of protein, in the blood. PKU patients must eat a highly restrictive low-protein diet. Without early treatment and monitoring, PKU can hinder brain development and impair cognitive functions. It is estimated that 13,500 people in America are living with this disease.
“There are a lot of patients who could benefit from this therapy. But the problem is that you have many, many mutations – more than a thousand – that cause this disease,” says Edward Kaye, MD, a pediatric neurologist and CEO of Aurora Therapeutics.
Crispr works by using a guide RNA to deliver an editing molecule to the desired location in the genome. Guide RNA is like a car’s GPS – it goes where it is programmed to go. In baby KJ’s case, scientists created a guide RNA to target her specific genetic mutation. Therefore his treatment works only for him.
Aurora’s strategy involves changing that guide RNA to create multiple versions of PKU therapy that address different mutations. Previously, the FDA would have considered each version an entirely new drug, each requiring its own clinical trials. But now, Aurora will be able to use the same technology platform to treat multiple mutations that cause PKU with less regulatory red tape.
Kaye says the company will use base editing, a more precise form of CRISP, and have a standardized process to streamline the design and manufacturing of its treatments.
“We are absolutely confident that there are no mutations left,” says Fyodor Urnov, co-founder of Aurora and a genome editing scientist at UC Berkeley. Urnov and several of his colleagues at Berkeley’s Innovative Genomics Institute, which Doudna founded in 2015, were involved in designing Baby KJ’s treatment.
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