CRISPR Success in Single Baby Highlights Rare Disease Treatment Challenges and Opportunities

A groundbreaking CRISPR treatment for an ultrarare genetic condition has brought hope to the rare disease community while simultaneously exposing the critical gaps in treatment development for extremely rare disorders. This development comes as the FDA considers new regulatory pathways for rare disease drugs, potentially reshaping the landscape for ultrarare disease therapies.

Unprecedented CRISPR Treatment Saves Infant with Ultrarare Condition

In a remarkable medical achievement, a nine-month-old boy named KJ has been successfully treated for CPS1 deficiency, an exceptionally rare genetic disorder affecting only 1 in 1.3 million infants born in the United States. The condition, which impairs the body's ability to process urea, can lead to permanent brain damage or death if left untreated.

The treatment, a single-use CRISPR therapeutic, was developed through an extraordinary collaboration of companies working pro bono or at reduced rates across North America. The therapy was manufactured at Aldevron's facility in North Dakota, with guide RNA provided by Integrated DNA Technologies in Iowa and nanoparticles from Acuitas Therapeutics in Vancouver. These components were assembled and administered at Children's Hospital of Philadelphia.

This success story highlights the potential of personalized genetic treatments for ultrarare conditions, often referred to as "n of 1" therapies. However, it also underscores the significant challenges faced in developing treatments for such rare disorders.

The Rare Disease Crisis: Gaps in Treatment and Development

Despite the breakthrough in KJ's case, the broader landscape for rare disease treatments remains bleak. According to Mark Veich, CEO of Advancium Health Network, a public charity focused on healthcare gaps, including medtech and rare diseases, "If you're a child who has a rare disease, one-third won't live to five years old. That itself is a crisis, a public health emergency."

Of the 30 million Americans with rare diseases, half are children. Most of these 15 million children have no FDA-approved treatments available. The situation is even more dire for ultrarare or "nanorare" diseases like CPS1 deficiency, where there is often no treatment pipeline at all.

The primary obstacle in developing treatments for extremely rare conditions is the lack of financial incentive for pharmaceutical companies. Veich explained, "Generally speaking, pharma companies tend to stay away from these very low prevalence diseases, especially n of 1 therapies." He added, "When pharma deprioritizes assets, 95% of the time it's because of economics, not the science."

As a result, treatments for ultrarare diseases are often funded through philanthropy, crowdfunding, or out of parents' pockets. This financial barrier creates a significant gap in the "discovery and development continuum" for rare disease therapies.

Potential Solutions and Future Outlook

Despite the challenges, KJ's successful treatment may signal positive changes in the rare and ultrarare disease space. Advancements in CRISPR and gene editing technologies are improving accuracy and efficacy, increasing the likelihood of producing successful, tolerable therapies for rare conditions.

Furthermore, regulatory bodies are beginning to recognize the need for more flexible approaches to rare disease drug approvals. FDA Commissioner Marty Makary has recently proposed a new regulatory mechanism for rare disease drugs, which would allow for conditional marketing based on a "scientifically plausible mechanism." While details are still forthcoming, this could potentially open doors for treatments targeting less common rare diseases.

Veich remains optimistic about the future of ultrarare disease treatments: "This CPS1 news just lets people know that with the right people, the right experts, the right partnerships, the right group of committed and like-minded people, these things can happen." As awareness grows and collaborations like the one that saved KJ become more common, there is hope that more children with ultrarare diseases will have access to life-saving treatments in the future.