Amicus Therapeutics bought a spinout of Nationwide Children’s Hospital last year as part of a plan to become a player in the emerging field of gene therapy. Today it is providing the first evidence, in humans, that the investment could pay dividends.
The results Amicus (NASDAQ: FOLD) are disclosing this morning come with plenty of caveats: it’s unclear, for instance, how long the apparent effects of the gene therapy it is developing, known as AAV-CLN6, might last. But they suggest that the treatment may at least have the potential to alter the course of Batten’s disease—a deadly inherited disorder—for patients with a particular genetic mutation.
Batten’s disease is a term for a group of rare disorders in which a genetic defect renders the body unable to make proteins that help clear out waste in brain cells. Abnormal material builds up in those cells, and brain function deteriorates over time, leading to a progressive loss of speech, movement, intellectual abilities, and ultimately an early death. The disease affects 2 to 4 out of every 100,000 children in the US, according to data from the National Institute of Neurological Disorders and Stroke.
There are no therapies that reverse Batten’s disease. The only available treatment is cerliponase alfa (Brineura), from BioMarin Pharmaceutical (NASDAQ: BMRN), which the FDA approved in 2017. Brineura is a chronic therapy that helps slow or stop symptoms in patients whose disease is triggered by a mutation to the CLN2 gene.
By acquiring Nationwide spinout Celenex for $100 million last year, Amicus gained access to experimental gene therapies for four other forms of Batten disease. AAV-CLN6 is the most advanced of the group, and as its name suggests, it is meant to treat Batten’s caused by a mutation to the CLN6 gene. The gene therapy is a one-time treatment that, when infused into the spinal fluid, delivers a healthy version of that gene into brain cells so it can produce a trash-removing protein that patients lack. The goal is to “fundamentally change the course of the disease in children,” says CEO John Crowley.
Amicus reports today that seven of eight patients to get AAV-CLN6 for up to 25 months ago have seen their disease stabilize, as measured by changes on a 6-point scale that evaluates their ability to walk and speak (known as the Hamburg Motor & Language Scale), one of the main goals of the study. Those patients were between 19 and 66 months of age at the start of the trial and had shown Batten symptoms before they got the gene therapy.
The seven patients to respond to AAV-CLN6 either maintained their Hamburg score or had a slight change—up or down 1 point—before stabilizing. That differs from “natural history” data compiled by Nationwide that suggest that patients’ Hamburg scores should decline by at least 2 to 3 points the first two years after CLN6 Batten’s patients show symptoms. Some patients in the study are also exhibiting a different disease trajectory than untreated siblings who had “substantial declines” in motor and language ability at the same age, Crowley said.
Most side effects seen were mild to moderate. There were three severe cases of vomiting or stomach pain that may have been associated with the gene therapy, but all three patients recovered. Amicus will disclose more details from the trial—including data for other key efficacy goals—at a medical meeting in October. Four other patients are enrolled in the study; Amicus hasn’t reported their efficacy results yet.
Still, Amicus believes that what it’s seen so far represents a “clinically meaningful” effect, says Crowley. The data show “strong evidence of stabilization of disease,” he says. “In younger children, this may mean the potential for them to live full healthy lives.”
That will have to be shown through further testing and longer follow-up. The path forward is unclear, though Crowley intends to meet with regulators and move quickly. “There is precedent for single studies to serve as registration trials” for gene therapies and drugs for rare disease with no approved treatments, he says. “Time is of the essence for all children living with this disease and we are moving with great haste on all fronts.”
For Amicus, the data represent the first look at the company’s bet on gene therapy, a field of research that is finally coming of age after decades of ups and downs. The FDA has already approved two gene therapies in the past few years—one for a rare form of inherited blindness and the other for the rare disease spinal muscular atrophy—and others could be on the way for hemophilia, Duchenne muscular dystrophy, and more.
It’s still unclear how long these treatments will last, what their commercial potential is, and whether society can pay for them. The SMA gene therapy Zolgensma, sold by Novartis (NYSE: NVS), for instance, costs more than $2 million and has to be paid through several installments.
Nonetheless, a number of companies, large and small, are betting on the future of gene therapy. Amicus, known for developing the chemical-based drug migalastat (Galafold) for Fabry disease, is among them. Over the past few years, it has amassed a portfolio of 12 gene therapy programs by tapping into research at two major gene therapy hubs—Nationwide Children’s Hospital in Columbus, Ohio, and the University of Pennsylvania. Four of those gene therapies are in clinical trials.
As Xconomy profiled earlier this year, Nationwide’s gene therapy work led to Zolgensma and several other programs being developed at companies like Sarepta Therapeutics (NASDAQ: SRPT) and Abeona Therapeutics (NASDAQ: ABEO). Amicus tapped into its work by buying Celenex, which was co-founded by Brian Kaspar—the scientific founder of AveXis, which developed Zolgensma—and Nationwide gene therapy researcher Kathrin Meyer. Both are now scientific advisors to Amicus. The Batten’s programs they developed use a similar approach to the SMA gene therapy.
Other, similar programs are progressing. Another Amicus Batten’s gene therapy for patients with a CLN3 mutation is in human testing. Two others for CLN8 and CLN1 mutations are in animal studies. Crowley wouldn’t say when to expect updates on the other programs.
Amicus will hold a conference call this morning to discuss the data.