FDA sets out advice to developers of gene editing medicines
The Food and Drug Administration advised developers of gene editing medicines to carefully assess potential safety risks in animal and human studies of their experimental treatments, issuing Tuesday draft recommendations that spell out the agency's thinking on research in the fast-moving field.
"While the potential of such products for the treatment of human disease is clear, the potential risks are not as well understood," the FDA wrote in the 19-page document, which follows previous recommendations for gene therapies that don't edit DNA directly.
Wall Street analysts who cover biotech companies developing gene editing treatments viewed the FDA's guidance as straightforward and without any major surprises. However, shares in one company, Verve Therapeutics, fell by more than 10% Tuesday on concerns the recommendations might affect its clinical trial plans.
The past year has brought the first clinical trial data for two CRISPR gene editing medicines used to alter the DNA of cells inside the body. The results, from Intellia Therapeutics and Editas Medicine, add to the gathering evidence supporting another CRISPR drug from CRISPR Therapeutics and Vertex that edits patient cells outside the body.
Behind those three companies — some of the first formed to use CRISPR to develop human medicines — are a growing group of biotechs seeking to edit DNA directly to treat disease. For example, Beam Therapeutics, which is exploring a more precise form of gene editing, recently began its first clinical study, while Verve plans to do the same later this year. The recommendations issued by the FDA Tuesday, which are in draft form and could be revised, are meant to help guide those companies as they move forward. "Over the past 10 years, the level of interest in human [gene editing] as a scientific technology used in the treatment of human disease has increased substantially, and there has been rapid development of gene therapy products incorporating [gene editing]," the FDA wrote. The guidance lays out the agency's understanding of specific gene editing components, as well as its expectations for how companies will manufacture and test them. In particular, the document details what information companies should provide the FDA when seeking clearance to begin human testing.
Many different gene editing techniques are covered by the guidance, including CRISPR as well as older methods such as zinc-finger nucleases and transcription activator-like effector nucleases. The guidance also applies to gene editing that doesn't involve breaking both strands of DNA, such as the base editing being advanced by Beam and Verve. Throughout the document, the FDA emphasizes the potential for unintended safety consequences to gene editing, such as "off-target" modifications, and advises companies on how to monitor and control for them. In clinical testing, for instance, the agency recommends that companies stagger the enrollment of study participants to better assess any side effects that might emerge.
Notably, the FDA also calls on companies to track trial volunteers for at least 15 years to study whether gene editing carries risks that only appear later. The agency called for similarly long follow-up in past guidance on gene replacement therapies.
On the whole, analysts viewed the document as unsurprising. Steven Seedhouse, of Raymond James, described it as "pretty straightforward" in a note to clients, while Stifel's Dae Gon Ha said it was "generally benign without layering any major burden on sponsors." However, one section of the guidance specified that companies should choose the patients they hope to treat carefully and generally recruit only those for whom no other acceptable treatments are available into "first-in-human" trials." That could potentially affect Verve, which is developing a gene editing treatment for heart disease.
Yet the FDA notes that "in some instances," patients with less advanced disease may be appropriate to enroll into first-in-human trials.
"We actually think [Verve's] strategy is aligned with the FDA given a stepwise approach focused on genetically defined diseases resistant to current [standard-of-care] first ... followed by secondary prevention in patients' [with] prior [cardiovascular] events and ultimately primary prevention," wrote Luca Issi, an analyst at RBC Capital Markets, in an investor note.
Published March 16, 2022
Ned Pagliarulo, Lead Editor