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Amicus’ latest positive update on Pompe drug hints at accelerated approval pitch

In the latest twist for what’s proved to be a year-long market thriller of dramatic ups and downs, Amicus Therapeutics CEO John Crowley today peeled the covers off an updated — and upbeat — look at how their drug ATB200/AT2221 performed in a Phase I/II study of Pompe disease. And he’s hinting that the positive results could pave the way to an accelerated approval — provided regulators are encouraging.

The key takeaways on this rare disease drug, Amicus’ $FOLD third clinical-stage program:

John Crowley

After posting mean initial improvements in a 6-minute walk test after 6 months of 38 meters and 52 meters for two groups of patients who had either been switched from enzyme replacement therapy or had never had ERT, the expanded group of patients now evaluable has reset those numbers at 35 meters and 42 meters. The 9-month data on a select group of patients is coming in now at 37 meters and 75 meters (for two ERT-naive patients).

Some erosion from the first set of results isn’t likely to dull analysts’ enthusiasm for the drug, while the 9-month data underscore the kind of snapshot on durability they’ll definitely like. But there was no control group for this study.

Amicus’ shares jumped 21% on the news.

Leerink’s Joseph Schwartz has been an enthusiastic observer. He noted:

The main question on investors’ minds will be whether Amicus will be able to file for regulatory approval based on these results. Recall, regulators have good exposure to Pompe disease thanks to Myozyme/Lumizyme, so while the Ph.1/2 study is not pbo.-controlled and is small in enrollment, ATB200/AT2221 could be another instance wherein the FDA exercises flexibility to expedite approval of a superior drug in a pt. population with an unmet need.

It’s still early days for a small study involving a rare disease, but Amicus is also touting evidence of improved strength among the subjects in the study. And researchers highlighted improvements in biomarkers of muscle strength to make their case that they’re right on track.

Forced vital capacity — a measure of pulmonary function — improved marginally for the ERT-naive group, rising 4.2% and 5% at 6 and 9 months, while the ERT-switch patients saw a slight decline.

“Very consistently,” Amicus CEO Crowley tells me, “they seemed to be getting much stronger. I don’t know where the numbers will specifically end up,” he adds, “but the magnitude of the improvement is really dramatic.”

The 6-minute walk test has been the center of attention among analysts, but Crowley says that physicians have spent just as much time looking at the biomarkers.

“These weren’t expected to get better,” says Crowley, who created Novazyme to develop an ERT for Pompe disease months after his daughter Megan was diagnosed with the disease as an infant. Genzyme later bought out Novazyme and Crowley went on to found Amicus, which set out to find a better therapy.

Right now the base case assumption is that the company will go ahead with a planned Phase III study next year, adds Crowley, stopping short of saying that the company would push for a quick OK on the Phase I/II data. But he adds that company execs will take the early-stage data to regulators and see what they think about pursuing a shorter path to an approval.

“The key (to accelerated approval) is manufacturing,” he adds. “We’ve invested enormous sums in scale up” to provide Phase III and commercial quantities of the drug. And he believes that’s put them in a good position with regulators, if they prove amenable.

Amicus and its investors have been through a roller coaster ride over the past year. The FDA spurned its application for its lead drug migalastat, demanding a new trial, even as European regulators provided a green light. Then Donald Trump was elected president, and after a little one-on-one lobbying by Crowley the FDA — now under Scott Gottlieb — told them they could go ahead and re-apply without the new study.

All that speaks positively of their odds in case they do shoot for a quick approval. But the year has also had its setbacks.

Just a few weeks ago, Amicus’ drug SD-101 failed a Phase III study, missing the co-primary and key secondary endpoints in treating epidermolysis bullosa.

A hit here will encourage more investors that there’s more wins than losses to focus on — giving Amicus a helping hand as it winds its way through some crucial pivotal milestones.

Mark Roberts, the principal investigator in the Pompe study, said:

“I believe that the results from this Phase 1/2 clinical study show striking improvements in functional measures and key biomarkers during the first six months of treatment, in addition to continued, further benefit out to nine months. I am especially intrigued by the six-minute walk distance and other motor function tests in the ERT-switch patients who historically have declining motor function following two or more years of treatment. These clinical data are compelling and suggest that ATB200/AT2221 has the potential to shift the treatment paradigm for Pompe disease.”


Image: Megan Crowley, daughter of Amicus CEO John Crowley, is recognized during President Donald Trump’s first address to a joint session of Congress on February 28, 2017. At 15 months old, Crowley was diagnosed with Pompe Disease and not expected to live more than a few short years. Megan, age 20, is now a sophomore at Notre Dame. Chris Kleponis / AP Images


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