chief medical officer Sukumar Nagendran distanced the company’s program from Wilson’s work. Nagendran said the UPenn studies used a different AAV virus than AveXis, and that the data are “inconsistent” with high-dose AAV studies from AveXis, Abeona, and Audentes. “The ‘process defines the product,’” Nagendran said in the statement. “Wilson’s manufacturing process is non-GMP”—a term that stands for industry-grade ‘good manufacturing practice’—“and is not the AveXis process.”
Terence Flotte, the dean of UMass School of Medicine and editor in chief of the journal Human Gene Therapy, was wary of drawing conclusions. He said that the small size of the UPenn studies and other variables could have affected the results.
“It’s important to get the information out there so that other groups can carefully study this,” Flotte said. But he doesn’t think testing of high-dose, systemic AAV therapy should stop—particularly when it comes to devastating afflictions like SMA or Duchenne, in which time lapsed can mean disease progression and death. In a commentary article published in the journal, Flotte called on the gene therapy community to “neither ignore, nor overreact to” UPenn’s findings.
Wilson’s concerns first emerged in Solid’s IPO prospectus. The company revealed on Jan. 16 that Wilson had resigned a few days earlier as the chair of its scientific advisory board over “emerging concerns about the possible risks” of the Duchenne gene therapy. In a separate filing last week, Solid disclosed that the FDA had partially suspended testing of the therapy, SGT-001, in November. Solid has not been able to administer a high dose to patients but is allowed to continue testing a lower dose.
Wilson declined to talk about Solid. But as Xconomy reported last week, other developers of Duchenne gene therapies say that preclinical tests haven’t produced any suggestions that human trials could have safety problems.
Jerry Mendell, the lead investigator in the early study of AVXS-101 at Nationwide Children’s Hospital in Columbus, Ohio, said the most significant issue was a spike in liver enzymes in four patients that was suppressed with steroids and didn’t lead to notable side effects. Meanwhile, he noted, the study featured children who survived beyond the age of two, instead of dying, and who were walking when they weren’t expected to.
“Does that mean that a patient will never have life threatening liver failure? No, I think this study definitely raises that concern,” says Charlotte Sumner, a Johns Hopkins Medicine professor who treats patients with SMA. While Sumner says there is “incredible excitement” about SMA gene therapy, at minimum she’d like to see more monitoring measures in future tests, such as peripheral and sensory nerve testing.
Beyond such monitoring, Wilson believes the gene therapy community must commit to “as much sharing and transparency of preclinical safety data” as possible.
“All of it is going to inform the field,” Wilson says.
