Dive Brief:

• Prime Medicine will soon begin the first clinical trial of a new drugmaking technique known as prime editing, following the Food and Drug Administration’s clearance of its application to start human testing.
• The regulatory green light, announced by Prime Monday, is an important early step for prime editing, which adapts CRISPR technology to rewrite defective genes without breaking both strands of the DNA double helix. It’s sometimes likened to a kind of genetic “word processor,” rather than the “scissors” analogy often used to describe standard CRISPR editing.
• Prime plans to first test its technology against a rare inherited condition known as chronic granulomatous disease. The company anticipates enrolling adults with stable disease in a Phase 1/2 study to assess whether its prime editing candidate PM359 is safe and works as intended.

Dive Insight:

FDA trial start clearances are usually a perfunctory exercise. But they take on greater significance when a new drug technology is being tested in humans for the first time.

The regulator has moved cautiously to green light studies of gene editing therapies, previously issuing halts to CRISPR Therapeutics, Beam Therapeutics and Verve Therapeutics when those companies sought to start their first trials.

That the agency cleared Prime’s initial request without a preliminary hold is a positive sign, according to Dae Gon Ha, an analyst at Stifel. “Our view is that FDA is increasingly comfortable with gene editing technologies,” Ha wrote in a note to clients. “What’s important is that with the … clearance, prime editing is one-step closer to becoming an important toolkit as a therapeutic.”

The clearance means prime editing will have gone from academic paper to human trials in about 4.5 years, as Prime co-founder and noted gene editing researcher David Liu pointed out on X.

While that’s fast, Prime has been under pressure to show the vast promise of its technology can translate to similarly sizable market opportunities. Company shares have declined steadily on doubts Prime will be able to prove that in the short term, particularly given its initial target of chronic granulomatous disease.

“The pushback/challenge here hasn’t been on the prime editing technology, but rather the [total addressable market] of [chronic granulomatous disease] as a first indication is on the smaller end of the spectrum to meaningfully excite investors,” wrote Ha.

Gene editing developers beyond Prime have faced similar questions, and companies like Beam, Verve and Intellia Therapeutics have seen their share prices fall over the past year.

Prime’s trial will follow participants for safety as well as biological markers of immune function and, over the longer term, resolution of the disease’s complications. Initial data is expected next year.

The company’s therapy consists of patient stem cells that are modified in a laboratory using prime editing to correct the disease-causing mutation. Between one in 100,000 to 200,000 people born in the U.S. are estimated to have chronic granulomatous disease, which is associated with susceptibility to infection and an array of autoimmune complications. Refractory or antibiotic-resistant infections are the most common cause of death among people with the condition.