▼ Summary
– A sick infant named KJ received a life-saving, personalized gene-editing treatment in February to correct a rare mutation causing toxic ammonia buildup.
– A new startup called Aurora Therapeutics, cofounded by Nobel laureate Jennifer Doudna, aims to scale such personalized treatments for rare diseases.
– Aurora will utilize a new FDA “plausible mechanism pathway” that allows approval based on data from just a few patients when large trials aren’t feasible.
– The company’s initial focus is treating phenylketonuria (PKU), a metabolic disorder with over a thousand different mutations, using a base-editing Crispr platform.
– This regulatory pathway lets Aurora treat multiple PKU mutations as variations of one platform, avoiding separate trials for each bespoke therapy.
A new biotech company, co-founded by Nobel laureate Jennifer Doudna, is pioneering a model for creating personalized gene-editing treatments for rare genetic disorders. This approach leverages a novel regulatory framework that could dramatically accelerate the approval of customized therapies, offering hope to patients with conditions that have been historically difficult to treat due to their rarity and genetic complexity.
The inspiration for this venture comes from a recent, remarkable case. Last year, an infant known as KJ received a life-saving, bespoke gene-editing therapy designed to correct a unique mutation causing a dangerous metabolic condition. Created in a mere six months, the treatment allowed the child to be discharged from the hospital, demonstrating the profound potential of personalized genetic medicine.
Now, the startup Aurora Therapeutics, co-founded by Crispr pioneer Jennifer Doudna, aims to systematically scale such treatments for a broader range of rare diseases. The company’s strategy is uniquely enabled by a new FDA regulatory pathway discussed by officials Marty Makary and Vinay Prasad. This “plausible mechanism pathway” allows for the approval of personalized treatments for severe, rare diseases based on data from only a small number of patients.
This shift is critical because traditional drug development requires large, costly clinical trials involving hundreds or thousands of participants. For ultrarare conditions, recruiting enough patients is often impossible. The new pathway provides a viable route to market when conventional randomized trials are not feasible. According to the framework, once a manufacturer shows success in several consecutive patients with different custom therapies, the FDA can move toward granting marketing authorization for the platform. Subsequent, similar therapies can then be approved using the accumulated data.
Aurora will initially target phenylketonuria (PKU), a metabolic disorder screened for at birth. PKU causes toxic levels of an amino acid to build up in the blood, forcing patients to adhere to a severely restrictive, low-protein diet for life. Without strict management, the disease can impair brain development and cognitive function. An estimated 13,500 people in the U.S. live with PKU.
“The challenge is the sheer number of genetic variations,” explains Edward Kaye, Aurora’s CEO and a pediatric neurologist. “There are over a thousand different mutations that can cause this single disease.”
This is where Aurora’s platform model becomes essential. Crispr gene-editing uses a guide RNA molecule like a genetic GPS to direct an editor to a precise location in the genome. For baby KJ, scientists designed a unique guide RNA targeting his specific mutation. Aurora’s plan involves creating a library of guide RNAs to address many different PKU-causing mutations, effectively generating multiple versions of a therapy from a single technological core.
Previously, each variant might have been regulated as an entirely new drug, each requiring its own separate clinical trial. Under the new regulatory approach, Aurora can use data from its platform to streamline approvals for therapies addressing different mutations within the same disease. Kaye notes the company will employ base editing, a more precise and efficient form of Crispr technology, and will standardize its design and manufacturing processes for speed and consistency.
“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 colleagues at the university’s Innovative Genomics Institute, founded by Doudna, were instrumental in designing the groundbreaking treatment for baby KJ, providing a direct proof-of-concept for Aurora’s ambitious mission.
(Source: Wired)
