FDA's gene editing guidance is 'par for the course' but still important, analysts say

“Par for the course.” “Benign.” “Not surprising.” These are some of the creative ways analysts described the FDA’s new guidance on gene editing for biotechs.

That said, the analysts are happy to see the FDA take some leadership and provide guidance to industry, which has already been chugging along developing gene editing therapies. With a baseline now in place, biotechs can hopefully avoid the drama and delays of clinical holds on their therapies.

So what did the FDA recommend in the new guidance? The agency provided a detailed list of information that companies should include in their investigational new drug applications to allow the assessment of safety and quality for the product. This includes product design, product manufacturing, product testing, preclinical safety assessment and clinical trial design.

According to analysts from Chardan, the recommendations could help streamline development of gene editing therapies and mitigate safety and tolerability concerns that can sometimes lead to clinical holds and delays to drug development timelines.

The FDA suggested patient selection for phase 1 trials should focus on those who do not have any other treatment options. This could mean that gene editing studies will need to be conducted abroad when a disease has an approved medication. Intellia Therapeutics is doing just that for the phase 1 study for its lead asset, transthyretin (ATTR) amyloidosis CRISPR therapy NTLA-2001, with sites in the U.K., Sweden and New Zealand. AATR amyloidosis has approved treatments from Alnylam and Pfizer.

With this fresh guidance, Verve Therapeutics may follow Intellia across the pond for studies on heterozygous familial hypercholesterolemia treatment VERVE-101. The company is planning to submit IND requests to the FDA in the second half of this year.

With that said, RBC Capital Markets said the door has been left open to move gene editing into less severe indications, and, with no clear guidance beyond those first-in-human studies, there could be some wiggle room to bring on other patients in later trials.

Shares of Verve dipped Tuesday after the guidance was released, a reaction analysts from William Blair called “overblown.” The company dropped from about $23 apiece Monday to $21 at Tuesday's close. While Verve’s therapy is in a common indication—cardiovascular disease—it remains the world’s No. 1 killer, so the company can still find a value proposition thanks to improved dosing and compliance that works within the FDA’s guidance. The shares were on the rise again as the markets opened Wednesday, adding more than 50 cents of value in the opening minutes.

The FDA recommended staggered dosing to monitor for any adverse events and that dosing should be prioritized by age. So adults, then adolescents and then pediatric patients. RBC noted that Editas Medicines is using this approach in a trial for a gene editing therapy under development for blindness caused by the degenerative eye disorder Leber congenital amaurosis 10. The company enrolled three cohorts of adults before moving into the pediatric population.

Chardan noted that the agency hasn't provided a clear cutoff for off-target editing frequency, which is when the gene editing therapy causes mutations or other unintended effects. The FDA is signaling that it’s open to considering the benefit and risk of a therapy, similar to how adeno-associated virus gene therapies have been treated. The guidance is, however, specific on the types of safety tests the agency wants to see to approve a preclinical asset for human testing.

All three of the analyst firms noted the guidance did not request liver biopsy data as a clinical endpoint for these therapies. The potential requirement for these invasive tests had been a concern for many in the gene editing class, according to RBC. But now that the FDA has signaled otherwise, the guidance is great news for Intellia, which may not have to produce such data for NTLA-2001. The company recently reported a second round of data for that asset on duration of effect as well as updated data on improvements in a key biomarker related to the disease.

Once a patient is in a trial, the FDA recommends 15 years of follow-up, a suggestion RBC says mirrors previous guidance to the industry.

Overall, RBC called the guidance incrementally positive for companies like Intellia, CRISPR Therapeutics, Editas, Beam Therapeutics, Verve, Caribou Biosciences and Graphite Bio. The worst-case scenarios had been the FDA requesting longer follow-up compared to gene therapy, a narrow focus on patients with no other alternatives and monitoring for off-target editing with liver biopsies.

Last month, gene editing was in the news after the U.S. Patent and Trademark Office ruled in favor of a group of patents from the Broad Institute of MIT and Harvard in a dispute over the patents around CRISPR gene editing technology. The decision brought into question Intellia's intellectual property, which comes from a different group of patents from the University of California, which brought the challenge.